Blood Podcast

Initial CHORUS data on HHT and ASH HematOmics Program Jul 23, 2026

In this week's episode, Blood editor Dr. James Griffin interviews Drs. Hanny Al-Samkari and Xin Zhou on their latest articles published in Blood. This episode highlights two important advances in hematology: the first report from the CHORUS registry for hereditary hemorrhagic telangiectasia (HHT) presented by Dr. Al-Samkari and also the introduction of the ASH Hematomics (ASHOP) platform for integrative genomic data analysis presented by Dr. Zhou. The CHORUS registry reveals that HHT is a progressive, underrecognized inherited bleeding disorder with a substantial burden of recurrent bleeding, iron deficiency, arteriovenous malformations, and life-threatening complications, while emphasizing the need for earlier diagnosis and the development of targeted therapies. The second presentation introduces ASHOP, an open-access platform that enables researchers to explore and integrate large-scale clinical and genomic datasets, facilitating discoveries in leukemia and other hematologic diseases through advanced analytical tools. Together, these studies demonstrate how comprehensive patient registries and innovative data-sharing resources are advancing precision medicine, improving disease understanding, and accelerating future research across hematology.

IV Iron during Acute Infection and Revisiting iTTP Refractoriness Jul 16, 2026

In this week's episode, Blood editor Dr. James Griffin interviews Drs. Haris Sohail and Lucas Kühne on their latest articles published in volume 147 issue 21 of Blood. In this CME article titled, "Retrospective, Real-World Study of IV Iron Use to Treat Iron deficiency Anemia During Acute Infection", Sohail et al show that IV iron given during acute infection with iron deficiency anemia is associated with improved 14-day and 90-day survival as well as hemoglobin recovery. Although this report has the limitations of a retrospective study, these findings challenge current practice and support randomized trials that include patients with infection. In "Revisiting Clinical Response and Refractoriness in Immune Thrombotic Thrombocytopenic Purpura", Kühne et al show in a multicenter registry study of 204 patients that refractoriness during caplacizumab treatment in immune TTP is uncommon and, when observed, is typically associated with confounding clinical factors. These findings underscore the importance of careful clinical reassessment and evaluation for alternative etiologies in patients with delayed platelet recovery, rather than attributing such cases to true treatment resistance.

A Pediatric ITP Risk Model and Targeting CD2 with CAR T-cell therapies Jul 09, 2026

In this week's episode, Blood editor Dr. Laura Michaelis interviews Drs. Kirsty Hillier and Marco Ruella on their latest articles published in Blood. For "Predicting Development of Pediatric Chronic Immune Thrombocytopenia at Disease Onset Using a Statistical Risk Model", Dr. Hillier shares the potential benefits of incorporating this new model to enhance the care of the 1 in 4 patients who develop chronic ITP. As an alternative to current guidelines which advise providers to "wait and see", this online model determines patients who are at risk for chronic ITP, allowing for providers to make informed decisions on their continued care. In "Harnessing the CD2 axis to broaden and enhance the efficacy of CAR T-cell therapies", Dr. Ruella explains how the treatment of T-cell neoplasms is limited by a lack of discriminating T-cell antigens that allow for effective antitumor responses while preventing CAR T-cell fratricide. The team found that CD2 was a viable target, especially combined with a novel PD-1:CD2 switch receptor to remedy dysfunction caused by CD2 deletion.

IV Iron Risks and Low-Dose AML Gains Jul 02, 2026

In this week's episode, Blood editor Dr. James Griffin interviews Drs. Heinz Zoller and Raul Ribeiro on their latest articles published in Blood. Dr. Zoller discusses "Ferric Carboxymaltose Increases Fracture Risk in Patients and Reduces Bone Formation in Mice with Iron Deficiency Anemia", and how these findings support consideration of alternative IV iron formulations that provide similar efficacy without risk of skeletal complications. Dr. Ribeiro discusses "A low-versus standard-dose regimen an induction for AML: a multicenter, randomized noninferiority trial" and how the low-dose regimen is associated with fewer toxicities, faster hematologic recovery, and reduced health care costs, suggesting a feasible treatment strategy for resource-limited settings.

Orca-T for GVHD–free survival and Understanding VEXAS anemia Jun 25, 2026

In this week's episode, Blood editor Dr. Laurie Sehn interviews Drs. Everett Meyer and Olivier Hermine on their latest articles published in volume 147 issue 11 of Blood. Dr. Everett Meyer discusses "Orca-T vs allogeneic hematopoietic stem cell transplantation (PRECISION-T): a multicenter, randomized phase 3 trial" which demonstrated that Orca-T showed superior chronic GVHD–free survival compared to the control arm (78.0% vs 38.4%, P < .001) and lower nonrelapse mortality (3.4% vs 13.2%, P = .03). Dr. Olivier Hermine shares insights from "VEXAS anemia is a mosaic erythroblastopenia" which proposes that VEXAS syndrome–associated anemia should be considered as a mosaic erythroblastopenia, in which the severity of anemia is influenced by the quality and quantity of the UBA1–wild-type compartment.

Treating AML, Before and After Relapse Jun 18, 2026

In this episode, Blood editor Dr. Laura Michaelis interviews Drs. Nigel Russell and Uwe Platzbecker on their articles published in volume 147 issue 10 of Blood. Dr. Russell discuses "CPX-351 vs daunorubicin, cytarabine, and gemtuzumab ozogamicin in older adults with non–adverse-risk AML: the NCRI AML18 trial" where a large randomized trial demonstrated that DA-GO2 provided greater overall survival as compared to CPX-351, and that further studies should compare DA-GO2 to lower-intensity venetoclax-based regimens. Dr. Platzbecker shares insights from the first prospective study to evaluate the clinical impact of early therapeutic intervention for MRD in "Azacitidine to treat measurable residual disease in patients with MDS/AML: final long-term results of the RELAZA2 trial" demonstrating potential therapies for patients to achieve and maintain remission.

Future Directions in Relapsed and Refractory Large B-cell Lymphoma Jun 11, 2026

In this week's episode, Blood editor Dr. Philippe Armand interviews Drs. Manali Kamdar and Nancy L. Bartlett on their latest review article published in Blood titled “From breakthroughs to blueprints: evolving evidence and future directions in relapsed and refractory large B-cell lymphoma”. They discuss the how the advent of chimeric antigen receptor T cells, antibody-drug conjugates, and bispecific antibodies all show major increases in efficacy over legacy chemotherapy-based regimens. They also share their insights on how to transform treatment paradigms in light of these breakthroughs.

Review Series on Clonal Tracking in Hematopoiesis Jun 04, 2026

In this Review series episode, Blood associateeditor Dr. Diane Krause interviews contributing authors from the Review Series on Clonal tracking in Hematopoiesis published in volume 147 issue 23 of Blood. Dr. Alejo E. Rodriguez-Fraticelli speaks to the development of his paper, "Clonal tracing of blood stem cells across mouse and human lifespans”, which provides a detailed overview of the experimental approaches that make clonal analysis possible, and which approaches are most appropriate to use to address specific questions. Dr. Shalin H. Naik speaks about how different clonal tracking approaches have been used to address the central question of clonal fate specification of stem and progenitor cells to specific lineages in “The evolution of hematopoietic models through a clonal lens”. Finally, Dr. Federico Gaiti speaks about “Methylation-based lineage tracing in cancer”, which takes these ideas into the context of cancer, focusing on how DNA methylation can be used to reconstruct clonal relationships.

New Approaches: Marstacimab Therapy and HLH Biomarkers May 28, 2026

In this week's episode, Blood editor Dr. James Griffin interviews Drs. Johnny Mahlangu and Joseph Rocco on their articles published in volume 147 issue 9 of Blood. Dr. Mahlangu discusses study details and next steps from "Efficacy and safety of marstacimab prophylaxis in hemophilia A/B with inhibitors: results from the phase 3 BASIS trial" which shows that bleeding was reduced by 93% with subcutaneous marstacimab. Dr. Rocco shares the development behind "CXCL9 as a novel prognostic marker to identify high-risk adults with hemophagocytic lymphohistiocytosis", and the insights gained from measuring a new surrogate marker of IFN-γ activity predicting severity and mortality.

Review Series on Hemophagocytic Lymphohistiocytosis (HLH) May 21, 2026

In this episode, Blood deputy editor Dr. Helen Heslop interviews contributing authors from the Blood review series on hemophagocytic lymphohistiocytosis. Drs. Nancy Berliner and Joanne Hsu join to provide insight on their paper, “Hemophagocytic lymphohistiocytosis in adults” discussing the importance of prompt diagnosis and treatment in this high-mortality disorder, and highlight emerging agents designed to modulate disease progression. Drs. Carl Allen and Bethany Verkamp reimagine diagnostic criteria through a threshold model in “Pediatric hemophagocytic lyphohistiocytosis: current conceptualization, diagnosis, and treatment”, in order to provide individualized therapies with the goal of addressing the combined influence of genetic susceptibility and environmental triggers.

IBD augmentation of CHIP and Platelet mTOR's impact on Cerebral Malaria May 14, 2026

In this week's episode, Blood editor Dr. Laurie Sehn interviews Drs. Reuben Kapur and Robert Campbell on their latest articles published in Blood. This episode highlights two groundbreaking studies exploring how inflammation drives serious blood and immune-related diseases. In the first interview, Dr. Kapur discusses how inflammatory bowel disease (IBD) can both promote and worsen clonal hematopoiesis of indeterminate potential (CHIP), with large-scale human data and mouse models identifying REF1 as a key mediator and potential therapeutic target. The second segment features Dr. Campbell, who explains how heme released during malaria infection activates platelet mTOR signaling, intensifying cerebral malaria and suggesting new avenues for platelet-targeted treatments. Together, the conversations reveal how inflammatory pathways and immune signaling contribute to disease progression while opening the door to novel precision therapies.

Long-term efficacy and safety of betibeglogene autotemcel for β-thalassemia May 07, 2026

In this week's episode, Blood editor Dr. Laura Michaelis interviews Dr. Alexis Thompson, former ASH president, on her latest article published in Blood. Dr. Thompson discusses "Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia." She explains transfusion-dependent β-thalassemia (TDT) requires rigorous, lifelong transfusion therapy and iron chelation to manage iron overload. Dr. Kwiatkowski and colleagues discuss the long-term efficacy and safety of this gene therapy in 63 patients with TDT, documenting sustained transfusion independence for up to 10 years and a safety profile consistent with that of myeloablative autologous transplantation.

Effects of ZNF467 on HSPC fitness and Promotion of Follicular Lymphoma via DC-SIGN Apr 30, 2026

In this week's episode, Blood editor Dr. James Griffin interviews Drs. Francesco Forconi and Bin Guo on their latest articles published in Blood. Dr. Guo shares insights from "Nucleoplasmic ZNF467 condensates boost hematopoietic stem cell engraftment via ICAM1-mediated mechanical reprogramming". The findings establish biomechanical regulation as an important determinant of stem cell identity and reveal new strategies for engineering stem cells with enhanced regenerative capacity. Then, Dr. Forconi discusses "DC-SIGN binding to the surface immunoglobulin oligomannose-type glycans promotes follicular lymphoma cell adhesion and survival". Persistent, low-level BCR engagement by DC-SIGN enables FL tissue retention and survival while avoiding the deleterious proapoptotic consequences of stronger, conventional antigen-driven BCR signaling. These findings help explain how FL cells exploit their microenvironmental niche.

Pathophysiology of ANKRD26-related thrombocytopenia and B-ALL recurrence after blinatumomab Apr 23, 2026

In this week's episode, Blood editor Dr. Laurie Sehn interviews Drs. Shengwen Calvin Li and Hrishi Krishna Srinagesh on their latest articles published in Blood. Dr. Li discusses "Single-cell profiling of ANKRD26 thrombocytopenia reveals progenitor expansion and polyploid apoptosis via JUNB-p21". The study identifies reproducible abnormalities in progenitor expansion and increased apoptosis of polyploid megakaryocytes, and they propose a novel mechanism in which centrosomal over-expression of ANKRD26 drives polyploid megakaryocyte apoptosis through JUNB-mediated induction of p21 transcription. Dr. Srinagesh discusses "Blinatumomab nonresponse correlates with poor survival after brexucabtagene autoleucel in B-cell ALL" in which data collected by the Real-World Outcomes Collaborative of CAR-T in Adult ALL consortium showed that prior nonresponse to blinatumomab was associated with inferior survival after brexucabtagene in comparison to blinatumomab-naïve patients. Early CAR-T responses were uniformly high regardless of prior exposure or response. This highlights that resistance to blinatumomab may identify patients at higher risk of post–CAR T relapse despite excellent initial responses.

Real-world availability of CAR T-cell therapies Apr 16, 2026

In this week's episode, Blood podcast editor Laurie Sehn interviews Drs. Edward Cliff on his latest research published in volume 147 issue 14 of Blood. Dr. Cliff discusses "Global access to commercial CAR T-cell therapies: a cross-sectional study of health technology assessment across the G20 countries" which maps the mismatch between innovation and implementation across high-income and selected-upper-middle-income countries for US Food and Drug Administration–approved products and indications.

Consequences of p53 loss and Gastrin for aGVHD of the Stomach Apr 09, 2026

In this week's episode, Blood podcast editor Dr. James Griffin interviews authors Drs. Steffen Boettcher and Robert Zeiser on their recent publications in Blood. Dr. Boettcher discusses "Bone marrow failure, somatic rescue by p53 inactivation, and enhanced leukemogenesis in germ line ERCC6L2 disease", which provides insights to disease evolution by demonstrating that p53 loss can rescue BMF phenotypes caused by biallelic mutations in ERCC6L2, but at the cost of profound genome instability, increasing DNA damage and leading to the onset of aggressive erythroid leukemia. Dr. Zeiser discusses "Gastrin for the treatment of acute graft-versus-host-disease of the stomach", which delineates the protective role of gastrin in aGVHD of the stomach in mice and patients and provides a rationale for therapeutic use of pentagastrin in a clinical trial for patients with aGVHD.

Review Series on Myeloproliferative Neoplasms Apr 02, 2026

In this episode, Blood Associate Editor Dr. Jason Gotlib discusses the Review Series "The New Wave of Targeted Therapeutics for MPN’s", with authors Drs. Stefan Constantinescu, Ann Mullally, and Marina Kremyanskaya. This Review Series covers 3 areas where exciting advances are occurring. Dr. Constantinescu discusses “Next-generation JAK inhibitors in the treatment of myeloproliferative neoplasms” which describes how new ways to switch off JAK signaling are delivering a suite of new small-molecule drugs with potential. Dr. Mullally discusses “Novel strategies targeting mutant calreticulin in essential thrombocythemia and myelofibrosis” which reviews the biology of calreticulin mutations in myelofibrosis and ET and how multiple different modalities can be brought to bear against this mutant surface protein, including monoclonal antibodies, bispecific T-cell engagers, and cellular and vaccine therapies. Dr. Kremyanskaya discusses “Modulators of the hepcidin pathway in polycythemia vera and myelofibrosis” which outlines the major recent progress being made in controlling excessive erythropoiesis through pharmacological modulation of iron metabolism.

CH in children with SCD and Asciminib for CML in the ASC4FIRST trial Mar 26, 2026

In this week's episode, Blood editor Dr. Laura Michaelis interviews Drs. Alexander Bick and Jorge Cortes on their latest papers published in Blood. Dr. Cortes, the current EIC of Blood Global Hematology discusses "Asciminib Demonstrates Superior Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia in the ASC4FIRST Trial" wherein the planned secondary analysis showed a further efficacy advantage and a consistently favorable safety profile for asciminib relative to investigator-selected TKIs, especially second-generation TKIs. Dr. Bick discusses "Increased prevalence of clonal hematopoiesis in children with sickle cell disease" where targeted sequencing for CH mutations in 2318 children with SCD and 2957 controls and found that children with SCD have a higher prevalence of CH, and majority of CH cases identified were very small “micro-CH” clones, more work is needed to define the clinical significance of these clones.

Emerging Mechanisms: Neutrophils and Immune thrombocytopenia from ICI Mar 19, 2026

In this week's episode of the Blood podcast, editor Dr. James Griffin interviews Drs. Christian Gorzelanny and Rebecca Leaf on their latest articles published in this week's issue of Blood. Dr. Gorzelanny discusses compelling evidence for a new mechanism that amplifies their proinflammatory actions in "Lipid nanotubes unmask neutrophils for complement attack", demonstrating the pathological role of this process in a range of inflammatory disorders in order to stimulate intense study of how to regulate nanotube formation for therapeutic benefit. In "Immune thrombocytopenia in patients treated with immune checkpoint inhibitors" Dr. Leaf and colleagues define the incidence, clinical features, and outcomes of ICI-induced immune thrombocytopenia. Showing that ICI-induced immune thrombocytopenia is associated with excess mortality, these data should provide an impetus to greater recognition and to protocolization of effective interventions.

Hepcidin-DMT1 interaction and GPRC5D-targeting bispecific antibody for MM Mar 12, 2026

In this week's episode, Blood editor Dr. Laura Michaelis interviews authors Drs. Marion Falabrègue and Ajai Chari on their papers published in volume 146 issue 24 of Blood. The work of Dr. Falabrègue and colleagues in "Intestinal hepcidin overexpression promotes iron deficiency anemia and counteracts iron overload via DMT1 downregulation" indicates that iron absorption from the apical surface of enterocytes can be modulated through manipulation of the hepcidin-DMT1 interaction, opening new avenues for research and therapeutic manipulation. "Talquetamab plus daratumumab in multiple myeloma" features a phase 1b/2 trial of 65 heavily pretreated patients with MM, where Chari et al combined daratumumab and talquetamab, a GPRC5D-targeting bispecific antibody, reporting depletion of CD38-expressing regulatory T cells following daratumumab and impressive efficacy, with an 80% overall (57% complete) response rate and median progression-free survival of 23.3 months. This regimen is now being evaluated in a phase 3 trial.

PETAL Consortium Survival Prognosticators and How Inflammation Impacts Hematopoiesis Mar 05, 2026

In this week's episode, Blood associate editor Dr. Laura Michaelis interviews Drs. Mark Sorial and Emmanuelle Passegue on their articles published in volume 147 issue 7 of Blood. Dr. Sorial discusses "Early time to relapse as a survival prognosticator in nodal mature T-cell lymphomas: results from the PETAL consortium" where he and his team evaluated the prognostic significance of early relapse in a large retrospective cohort. They report a time to relapse of <12 months as a strong predictive factor independent of the prognostic index for T-cell lymphoma and histology, with results validated in 2 independent cohorts. Dr. Emmanuelle Passegue discusses "Inflammation perturbs hematopoiesis by remodeling specific compartments of the bone marrow niche". Using a combination of single-cell RNA sequencing profiling and flow cytometry, the team characterized the bone marrow niche compartments in mice subjected to inflammation. They show that inter-feron-mediated inflammation preferentially targets central marrow leptin receptor–expressing mesenchymal cells, triggering cytokine release that affects monocyte dynamics in the bone marrow microenvironment.

Review Series on the Structural Underpinnings of Hemostatic Plugs and Thrombotic Occulsions Feb 26, 2026

This review series focuses on recent advances in resolving macro and molecular structures that have driven the field of occlusive thrombus structure and function forward. Covering multiple contributions to thrombosis, eg, platelets, factor XIII, and the contact system, the series also looks to put this new knowledge into the context of future advances in diagnostic and therapeutic tools to enhance normal hemostasis while preventing and treating unwanted thrombosis. Blood Associate Editor, Dr. Thomas Ortel discusses this series with Drs. Alisa Wolberg, Jonas Emsley, and John Weisel, who all contributed to articles in the Review Series on the Structural Underpinnings of Hemostatic Plugs and Thrombotic Occulsions which can be found in volume 146, issue 12 of Blood.

VTE Risk Model in Children and a Novel Tri-specific T-cell-engager for MM Feb 19, 2026

In this week's episode, Blood editor Dr. Laurie Sehn interviews authors Drs. Julie Jaffray and Ulrike Philippar on their latest articles published in Blood. Dr. Jaffray discusses her CME article, "Multisite validation of a venous thrombosis risk model in critically ill children through the CHAT Consortium", identifying patients with risks as high as 17% and taking research one step closer to the goal of personalized thromboprophylaxis for safe and effective care of high-risk children. Dr. Philippar discusses her article "Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models", where the extensive in vitro and in vivo preclinical studies with cell lines and patient samples indicate strong potential for this agent to have efficacy against MM expressing either or both of these antigens.

CAR-iNKT cell immunotherapy and Jagged2/Notch regulation of HSC Feb 12, 2026

In this week's episode, Blood editor Dr. Laurie Sehn interviews authors Drs. Anastasios Karadimitris and Maria Carolina Florian on their papers published in Volume 147 Issue 2 of Blood. Dr. Karadimitris' paper "Off-the-shelf dual CAR-iNKT cell immunotherapy eradicates medullary and leptomeningeal high-risk KMT2A-rearranged leukemia", discusses the success of bispecific CAR-iNKT cells targeting CD19 and CD133 in pre-clinical models, prompting the clinical development of this class of product. Dr. Florian's paper, "A Notch trans-activation to cis-inhibition switch underlies hematopoietic stem cell aging" proposes that the Jagged2/Notch interaction is a key regulator of hematopoietic stem cell divisional symmetry during aging and offers insights that may inform strategies to restore regenerative function in aged hematopoiesis.

Biologic Insights and Clinical Trial Design for AML Feb 05, 2026

In this week's episode, Blood editor Dr. James Griffin interviews Drs. Paresh Vyas and Andrew Hantel on their research published in this week's issue of Blood. Dr. Vyas discusses his paper, "Rapid clonal selection within early hematopoietic cell compartments presages outcome to ivosidenib combination therapy", which provided new insights as to when and how to intervene to circumvent resistance to AML remission. Dr. Hantel will speak about his paper, "Impact of Modernizing Eligibility Criteria on Enrollment and Representation in AML Clinical Trials". For a real-world cohort of more than 2200 patients with AML, they reported that modernized, safety-based criteria could nearly double trial eligibility, with especially pronounced gains among historically underserved groups. Both studies highlight how biologic insight and thoughtful trial design can drive more effective, inclusive advances in AML treatment and research.

How I Treat Series on Acute Lymphoblastic Leukemia Jan 29, 2026

In this week's episode, Blood Associate editor Dr. Hervé Dombret interviews authors Drs. Sarah K. Tasian and David T. Teachey on their contributions to the How I Treat Series on acute lymphoblastic leukemia. Dr. Tasian's paper, “How I treat Philadelphia chromosome-like acute lymphoblastic leukemia in children, adolescents, and young adults” discusses the different classes of Ph-like ALL and reviews the recent trials investigating TKIs and immunotherapy specifically for this high-risk patient population. Dr. Teachey's paper, “How I treat ETP-ALL in children”, discusses the best current and emerging therapies that may be used in patients with ETP ALL, including nelarabine and other new agents, immunotherapy, and allogeneic HSCT.

See the full How I Treat series in volume 145 issue 1 of Blood.

How I Treat Series on the 25th anniversary of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia Jan 22, 2026

In this week's episode, Blood Associate Editor, Dr. Jason Gotlib leads a discussion about the How I Treat Series commemorating the 25th anniversary of the introduction of tyrosine kinase inhibitors in CML, featuring Drs. Neil Shah, Simona Soverini, Elisabetta Abruzzese, and Yves Chalandon. The introduction of TKIs revolutionized patient outcomes in CML, turning a poor prognosis—3 to 5 years life expectancy—to a manageable chronic condition. In this conversation, we'll cover management techniques for CML during relapse, pregnancy, and explore indications for hematopoietic stem cell transplantation.

See the full How I Treat series in Volume 147 issue 4 of Blood.

How I Treat Series on Hematologic Complications in Pregnancy Jan 15, 2026

In this week's episode, Blood Associate editor Dr. Thomas Ortel interviews authors Drs. Ware Branch and J.J. Strouse on their contributions to How I Treat hematologic complications in pregnancy. Dr. Branch's paper, “How I diagnose and treat antiphospholipid syndrome in pregnancy” discusses the evolving clinical and laboratory features of APS, and the treatment of cases meeting ACR/EULAR classification criteria. Dr. Strouse stresses the unique problems posed to both the mother and fetus during pregnancy in his paper "How I treat sickle cell disease in pregnancy”.

See the full How I Treat series in volume 143 issue 9 of Blood journal.

Review Series on Marginal Zone Lymphoma Jan 08, 2026

This week's episode accompanies the Review Series on Marginal Zone Lymphoma published in this week's issue of Blood. Associate editor, Dr. Philippe Armand interviews authors Dr. Juan Pablo Alderuccio and Dr. Ariela Noy on their contribution to this review series titled "The treatment of marginal zone lymphoma". The article is crucial in highlighting the clinically and biologically heterogenous nature of MZL diseases, and how current treatment options and available research do not allow for comprehensive MZL specific therapies. Drs. Alderuccio and Noy share their insights on specific avenues for the expansion of the MZL care landscape.

Find the full review series in volume 147 issue 2 of Blood journal.

VTE Recurrence Risk Factors and poor-response AML Transplant Outcome Indicators Jan 01, 2026

In this week's episode we've pulled a vault recording from 2025! Blood editor Dr. Laurie Sehn interviews authors Drs. David-Alexandre Trégouët and Johannes Schetelig on their research published in volume 146 issue 19 of Blood journal. Dr. Trégouët's study conducted a genome-wide association study supplemented by transcriptome and Mendelian randomization analyses to identify 28 loci and proteins associated with VTE recurrence risk. This work provides genomic evidence that inherited variants contribute to the risk of VTE recurrence, raising the possibility of a more personalized approach to the prevention of recurrent VTE. The study conducted by Dr. Schetelig and colleagues report the results of a long term trial on patients with poor-response AML, comparing outcomes between patients who received salvage chemotherapy versus immediate transplantation. With no difference in survival rates at 5 years, outcomes seem to be determined mainly by genetic risk factors, age, and comorbidities, therefore challenging the routine use of intensive remission induction before allogeneic transplant in patients with an available donor and underscore the need for novel therapeutic strategies for poor-risk AML.

Featured Articles:

Novel Treatment Targets for Hemophilia A and AML Dec 25, 2025

In this week's episode, Blood editor Dr. James Griffin interviews authors Drs. Vincent Muczynski and Mark Geyer on their latest research published in Blood. Dr. Muczynski's research asks if there could there be a better gene than the factor VIII (FVIII) gene to transfer for curative treatment of hemophilia A? Dr. Geyer then explores CAR T cells armed with interleukin-18 (IL-18) secretion that target CD371, a transmembrane glycoprotein with high expression on AML and leukemia-initiating cells. Both studies explore finding novel targets for these powerful treatment modalities.

Featured Articles:

Novel Differentiation Therapies for AML and Prognostic Value of PET in MM Dec 18, 2025

In this week's episode, Blood editor Dr. Laurie Sehn interviews three of the latest Blood authors: Drs. Vijay Sankaran, Ruud Delwel, Françoise Kraeber-Bodere. Two studies on the MECOM gene have been paired in this episode, analyzing new groundwork for potential novel myeloid differentiation therapies via repression of MECOM restoring enhancer mediated CEBPA expression. We'll also hear about the results of CASSIOPET, imaging companion study of the CASSIOPEIA trial, and how achieving negativity in PET before starting maintenance therapy is significant even in patients who still show residual disease in the bone marrow.

Featured Articles

Review Series on Platelet Heterogeneity Dec 11, 2025

In this Review Series episode, Blood Associate Editor, Dr. Elisabeth Battinelli discusses the Platelet Heterogeneity with authors Drs. Craig Morrell, Larry Frelinger, and Leo Nicolai.

Find the full review series in volume 146 issue 24 of Blood.

Special Episode: Maternal Health in Hematology Dec 05, 2025

In this special episode, Blood editor Dr. Laura Michaelis interviews Dr. Arielle Langer and Blood Associate editor Dr. Marc Blondon for this special Maternal Health episode. In honor of the second Maternal Health compendium, both discuss their papers featured in this special collection.

Featured Articles:

See the entire Maternal Health Compendium Second Edition

Analysis of IELSG37 Trial Results and PF4 in Stem Cell Aging Dec 04, 2025

In this week's episode, Blood editor Dr. James Griffin speaks with Drs. Emanuele Zucca and Sandra Pinho about their latest articles published in Blood. Dr. Zucca discusses his second analysis of the IELSG37 trial, where findings suggested that R-CHOP21 rituximab, cyclophosphamide,
doxorubicin, vincristine, and prednisone, administered every 21 days) may be a suboptimal frontline regimen for PMBCL. Dr. Pinho discusses the aging megakaryocytic niche and its influence on the age-associated decline in HSC and progenitor cell function. The authors demonstrate that remodeling of the megakaryocytic niche and associated platelet factor 4 (PF4) downregulation are central mechanisms driving HSC aging.

Featured Articles:

Fixed-Duration Epcoritamab Combination Therapy for Relapsed or Refractory Follicular Lymphoma and Pre-Transplant Strategies for GVHD post-HSCT Nov 27, 2025

In this week's episode, Blood editor Dr. Laurie Sehn interviews authors Drs. Lorenzo Falchi and Robert Levy on their latest papers published in Blood Journal. Dr. Falchi discusses his work on an open-label, multicenter phase 1b/2 study evaluating fixed-duration epcoritamab with rituximab and lenalidomide in 108 patients with relapsed or refractory follicular lymphoma. Dr. Levy shares his work on demonstrating that in vivo expansion of Tregs in recipients prior to transplant is possible by activating TNFRSF25 (also known as death receptor 3) in combination with low-dose interleukin-2 in preclinical models. Both papers showed impressive and promising results for the treatment of lymphoma and GVHD.

Featured Articles

Advancing Blood Disorder Treatments Through Precision Therapeutics Nov 20, 2025

In this week's episode, Blood editor Dr. Laura Michaelis interviews authors Drs. Terri Parker and Peter Lenting on their latest papers published in Blood Journal. Dr. Lenting discusses his work on introducing a new therapeutic approach to von Willebrand disease with the development of a novel bispecific antibody (KB-V13A12) that links endogenous mouse VWF to albumin, extending VWF half-life twofold with cessation of provoked bleeding. Dr Parker shares the results of a 43-patient phase 2 study that evaluates the single agent isatuximab, a CD38 monoclonal antibody, in patients with relapsed/refractory AL amyloidosis. With a hematological response rate of 77%, organ response rates between 50 and 57%, and an excellent safety profile, the current study lays the foundation for future use of isatuximab across treatment settings and combination strategies.

Featured Articles

New Research: Mitochondrial DNA in TRALI and Venetoclax-Obinituzumab in CLL Trials Nov 13, 2025

In this week's episode, associate editor Dr. James Griffin interviews researchers Dr. John Semple and Dr. Othman Al-Sawaf on their groundbreaking studies on transfusion-related acute lung injury and chronic lymphocytic leukemia treatment. Dr. Semple explored how mitochondrial DNA could act as a first hit in lung injury, while Dr. Al-Sawaf revealed that patient fitness may not significantly impact the efficacy of targeted CLL treatments. Both studies challenge existing medical assumptions and suggest new approaches to understanding disease mechanisms and treatment responses.

Featured Articles

Bispecific Antibodies in Aggressive B-Cell Lymphoma: Real-World Insights and Future Directions Nov 06, 2025

In this week's episode, Blood editor Dr. Laura Michaelis interviews author Dr. Taylor Brooks on his latest paper published in volume 146 issue 18 of Blood Journal. The conversation discusses outcomes of bispecific antibodies (epcoritamab or glofitamab) in treating aggressive B-cell lymphoma in a study with 245 patients. Findings show a tentative way forward in treatment for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Featured Articles

A novel cause of type 1 von Willebrand disease: impaired exocytosis of Weibel-Palade bodies due to biallelic MADD variants
Sophie Hordijk, Stijn A. Groten, Petra E. Bürgisser, Sebastiaan N. J. Laan, Georg Christoph Korenke, Tomáš Honzík, Diane Beysen, Frank W. G. Leebeek, Paul A. Skehel, Maartje van den Biggelaar, Tom Carter, Ruben Bierings
Sequential targeting in multiple myeloma: talquetamab, a GPRC5D bispecific antibody, as a bridge to BCMA CAR-T therapy
Binod Dhakal, Othman S. Akhtar, David Fandrei, Alexandria Jensen, Rahul Banerjee, Darren Pan, Shambavi Richard, Reed Friend, Matthew Rees, Patrick Costello, Mariola Vazquez Martinez, Oren Pasvolsky, Charlotte Wagner, James A. Davis, Omar Castaneda Puglianini, Ran Reshef, Aimaz Afrough, Danai Dima, Manisha Bhutani, Omar Nadeem, Ricardo Parrondo, Ciara Freeman, Lekha Mikkilineni, Shahzad Raza, Larry D. Anderson Jr, Prashant Kapoor, Hitomi Hosoya, Saurabh Chhabra, Ariel Grajales-Cruz, Mahmoud Gaballa, Shonali Midha, Melissa Alsina, Douglas Sborov, Krina Patel, Yi Lin, Christopher Ferreri, Nico Gagelmann, Anupama Kumar, Doris Hansen, Andrew Cowan, Luciano J. Costa, Maximilian Merz, Surbhi Sidana

Spotlight on Acute Myeloid Leukemia Oct 16, 2025

In this Spotlight series episode on Acute Myeloid Leukemia, Blood Editor, Dr. Selina Luger interviews Drs. Laura Michaelis and Alexander Perl on their paper in the series titled “The fit older adult with acute myeloid leukemia: clinical challenges to providing evidence-based frontline treatment”. The conversation explores challenges in treating AML across different patient populations. They also focus on treatment approaches for fit older adults with AML, highlighting the need for less toxic therapies and ongoing randomized trials to better understand treatment efficacy.

See the full spotlight series on Acute Myeloid Leukemia in Volume 145 Issue 24 of Blood journal.

Busulfan-melphalan conditioning in newly diagnosed, transplant-eligible multiple myeloma; and use of spatial transcriptomics to probe the three-dimensional properties of multiple myeloma bone marrow microenvironments Oct 14, 2025

In this week's episode we’ll learn more about a study comparing busulfan-melphalan with melphalan alone as the conditioning protocol for newly diagnosed, transplant-eligible multiple myeloma; then we will discuss data on how three-dimensional transcriptomics can reveal complex interactions between plasma cells and bone marrow microenvironments.

Featured Articles

How I Treat Wiskott-Alrich syndrome Oct 02, 2025

In this How I Treat podcast episode, Laura Michaelis, MD interviews Sung-Yun Pai, MD about their recently published article in Blood journal "How I treat Wiskott-Alrich syndrome". They highlight recent updates in treatment, including new risk-benefit calculations due to safer treatments and longer follow-ups. Challenges include late diagnosis, lack of well-matched donors, and limited gene therapy availability. They emphasize the importance of early referral to specialized centers and the need for discussions about curative intent therapies, including transplant and gene therapy. The conversation also covers the complexities of gene therapy, such as the need for better conditioning agents and the challenges of achieving full correction in all cell types.

Use of Marstacimab for Prophylaxis in hemophilia A and B; matched-donor allogeneic CD19 CAR-T in adult B-ALL; a new prognostic index for T-cell cutaneous lymphomas Oct 02, 2025

In this week's episode we'll learn about targeting the tissue factor pathway inhibitor with a monoclonal antibody to rebalance HEMOSTASIS in hemophilia A and B. In the phase 3 BASIS trial, the monoclonal antibody marstacimab reduced bleeding events, and was generally well tolerated, with no unanticipated side effects. After that: matched-donor allogeneic CD19 CAR-T for adult B-ALL. Given after allogeneic transplantation, CAR-donor lymphocyte infusion after lymphodepleting chemotherapy was associated with favorable efficacy and a tolerable safety profile. Finally: a new prognostic index for mycosis fungoides and Sézary syndrome. Comprised of four prognostic factors, the “CLIPI” could enable more personalized treatment of cutaneous lymphomas, identifying patients who may benefit from intensified treatment.

Featured Articles

Epstein-Barr virus genomic variants in human disease states, somatic GATA1 mutations and leukemia in Down syndrome, and new definitions for high-risk multiple myeloma Sep 25, 2025

In this week's episode, we’ll learn more about relationships between Epstein-Barr virus genomic variants and human diseases, including hematological malignancies; the presence and timing of somatic GATA1 mutations and their relationship to a Down syndrome-specific form of leukemia; and new definitions for high-risk multiple myeloma that emphasize the presence of two or more high-risk cytogenetic abnormalities.

Featured Articles:

Review Series on Acute Lymphoblastic Leukemia (ALL) Sep 18, 2025

In this Review Series episode, Associate Editor Dr. Hervé Dombret speaks with Dr. Mark Litzow about the latest immunotherapy advances for Acute Lymphoblastic Leukemia (ALL). The discussion highlights innovative treatments like blinatumomab and inotuzumab, which are showing remarkable success in clinical trials, including an 85% three-year survival rate and over 90% complete remission in elderly patients. Researchers are focusing on reducing chemotherapy intensity, developing personalized treatment approaches, and identifying optimal immunotherapy strategies for different ALL subtypes. The conversation underscores a promising shift towards more targeted, less toxic treatments that could significantly improve patient outcomes across various age groups and disease characteristics. These emerging therapies represent a potential paradigm shift in ALL treatment, offering hope for more effective and less aggressive therapeutic interventions.

Read Dr. Litzow's paper “Incorporation of immunotherapy into frontline treatment for adults with B-cell precursor acute lymphoblastic leukemia” or find the whole review series on acute lymphoblastic leukemia in volume 145 issue 14 of Blood Journal.

Azacitidine holds promise in VEXAS syndrome; a step forward in precision blood matching; identifying a new vulnerability in TP53-mutated AML Sep 18, 2025

In this week's episode we'll learn about Azacitidine in VEXAS syndrome. Treatment can provide responses in patients with this complex autoinflammatory disorder. But relapse rates were high, so long-term therapy may be required to maintain disease control. After that: A step forward in precision blood matching. High-throughput array genotyping enables extended matching to reduce antibody formation. The results show the potential for reducing harm in regularly transfused patients. Finally, identifying a new vulnerability in TP53-mutated AML. Loss of the tumor suppressor BAP1 defines a unique subtype of TP53-mutated de novo AML. BAP1 loss also confers sensitivity to BCL-xL inhibitors in vivo, opening a new therapeutic avenue.

Featured Articles

Diffuse large B-cell lymphoma’s long-term effects on immune profiles, plasminogen activation and prevention of venous thromboembolism, and PARP inhibitors in hematological malignancies carrying epigenetic mutations Sep 11, 2025

In this week's episode we'll learn about persistent changes in immune profiles in patients who have had diffuse large B-cell lymphoma, or DLBCL, and other cancers; that plasminogen activation and plasmin activity do not appear to play a role in routine physiological prevention of venous thromboembolism, or VTE; and about a novel mechanism that makes hematological malignancies carrying epigenetic mutations susceptible to PARP inhibitors.

Featured Articles:

“Ironing out” Tet2-mutant HSPCs; A CAR-T “license to kill” in T cell leukemia/lymphoma; insights on cHL genetics, through the lens of ctDNA Sep 04, 2025

In this week's episode, we'll learn about how TET2 is often mutated in myeloid malignancies and clonal hematopoiesis. In new work, expansion of Tet2-mutant HSPCs was dependent on Ncoa4, the cargo receptor mediating ferritinophagy. We’ll iron out the implications. After that: a double-oh-seven license to kill in T-cell leukemia/lymphoma. WU-CART-007 is an off-the-shelf CAR T product with manageable safety and encouraging efficacy. With further work, it could become a new option for patients in urgent need of therapy. Finally: a comprehensive genetic study of classical Hodgkin lymphoma using circulating tumor DNA. This new research provides novel and complex insights on genetic subtypes, prognostic biomarkers, neoantigens in the disease environment, and more.

Featured Articles:

Targeting NPM1 in AML with a menin inhibitor; in primates, a CD137 ADC eliminates acute GVHD Aug 28, 2025

In this week's episode we'll learn about targeting NPM1 in acute myeloid leukemia. Researchers report the first clinical evidence of a menin inhibitor inducing complete remissions in AML with a NPM1 mutation. This validates NPM1 as a new therapeutic target in AML, alongside FLT3, IDH1/2, and KMT2A. Also on the podcast: targeting CD137 to prevent graft-versus-host disease. In nonhuman primates, a single dose of a CD137 antibody-drug conjugate provided long-term protection, with one important caveat: the potential for viral reactivation.

Featured Articles:

How I Treat Series on Iron Overload in Hematologic Disorders Aug 28, 2025

Blood Editor, Dr. Thomas Coates interviews Dr. Emanuele Angelucci on his paper, "How I manage iron overload in the hematopoietic cell transplantation setting" which is featured in Blood's "How I Treat Series on Iron Overload in Hematologic Disorders".

See the full How I Treat series in volume 145 issue 4 of Blood.

Early prediction of follicular lymphoma patients with poor survival; immune hotspots in aplastic anemia; role of allo-transplant for Hodgkin lymphoma in the checkpoint inhibitor era Aug 21, 2025

In this week's episode we'll learn about how by combining PET response with circulating tumor DNA, or ctDNA, in newly treated patients with follicular lymphoma, investigators identify those patients likely to progress within 24 months of initial treatment, also known as POD24. After that: Immune hotspots in aplastic anemia. These newly identified hotspots potentially represent sites in the bone marrow where the active immune response takes place, driving the destruction of hematopoietic stem and progenitor cells. Finally, allogeneic transplantation for Hodgkin lymphoma in the checkpoint inhibitor era. In a large, retrospective study, patients with prior checkpoint inhibitor exposure had remarkable outcomes, particularly when post-transplant cyclophosphamide was used.

Featured Articles:

Exogenous CD19 stimulation in B-cell acute lymphoblastic leukemia treated with CD19 CAR T-cell therapy, sequential rapid immune-assay in heparin-induced thrombocytopenia diagnosis, and new survival prediction models for chronic myelomonocytic leukemia Aug 19, 2025

In this week's episode, we’ll learn more about how exogenous CD19 stimulation affects CAR T-cell persistence in B-cell acute lymphoblastic leukemia treated with CD19 CAR T-cell therapy; new algorithms that incorporate sequential rapid immune-assays, intended to improve diagnosis of heparin-induced thrombocytopenia, and resource-adaptive survival prediction models to help guide management of patients with chronic myelomonocytic leukemia.

Featured Articles:

How I Treat series on Acute Myeloid Leukemia Aug 14, 2025

In this episode, Associate Blood editor Dr. Selina Luger leads a discussion with Drs. Courtney DiNardo, Eunice Wang, Andrew Wei and Gail Roboz about the advances in treatment options for Acute Myeloid Leukemia (AML). The conversation highlights new combinations like Venetoclax-azacitidine, challenges with differentiation syndrome, and emerging strategies for secondary AML patients. The authors emphasize moving beyond traditional one-size-fits-all treatments to more nuanced, patient-specific care that considers individual genetic profiles and potential complications. These insights provide a comprehensive overview of the latest innovations in AML treatment, offering healthcare professionals critical updates on managing this complex disease.

See the full How I Treat series on Acute Myeloid Leukemia in volume 145 issue 12 of Blood journal.

Daratumumab maintenance in newly-diagnosed, transplant-eligible multiple myeloma; the role of neutrophils in myeloproliferative neoplasms; and novel genetic loci associated with the risk of heavy menstrual bleeding Aug 07, 2025

In this week's episode, we’ll learn more about the effects of daratumumab maintenance on minimal residual disease in patients with newly diagnosed, transplant-eligible multiple myeloma; the role of neutrophils in the pathophysiology of myeloproliferative neoplasms; and a genome-wide association study that identified novel genetic loci associated with the risk of heavy menstrual bleeding.

Featured Articles

Hematopoietic stem cells with enhanced transplantability, ruxolitinib for refractory macrophage activation syndrome, and magrolimab in newly diagnosed acute myeloid leukemia Jul 31, 2025

In this week's episode we'll learn more about enhanced transplant characteristics; targeting the JAK-STAT pathway with ruxolitinib in patients with adult-onset Still’s disease and macrophage activation syndrome; and a pair of trials demonstrating lack of benefit for the anti-CD47 monoclonal antibody magrolimab in newly diagnosed acute myeloid leukemia.

Featured Articles

A JAK inhibitor for CRS and ICANS prevention; ChAdOx1-platelet interactions and post-vaccination arterial thrombosis; lineage switch, an emerging mechanism of leukemia relapse Jul 24, 2025

In this week's episode, we'll learn about a JAK inhibitor to prevent complications of CD19-directed CAR T-cell therapy. In a phase 2 study, itacitinib was well tolerated and demonstrated promising reductions in the incidence of cytokine release syndrome and neurotoxicity. After that: investigators report direct interactions between ChAdOx1 and platelets under arterial shear conditions. Investigators say it’s a novel biophysical mechanism that potentially contributes to post-vaccination arterial thrombosis. Finally, we explore lineage switch, an emerging form of acute leukemia relapse with dismal outcomes. It arises rapidly following antigen-targeted immunotherapy, highlighting the importance of advanced methods for detection and treatment.

Featured Articles:

Ruxolitinib plus dexamethasone in newly diagnosed adult hemophagocytic lymphohistiocytosis; lysine-specific demethylase-1 inhibitors in sickle cell disease; and clinical characteristics of patients with low von Willebrand factor Jul 21, 2025

In this week's episode we’ll learn more about the use of ruxolitinib plus dexamethasone to treat newly diagnosed patients with adult hemophagocytic lymphohistiocytosis; lysine-specific demethylase-1 inhibitors as a potential new class of therapies for sickle cell disease and other beta-globinopathies; and insights into clinical characteristics of patients with von Willebrand factor levels that are lower than normal but higher than those typically used to diagnose von Willebrand disease.

Featured Articles:

Review series on mantle cell lymphoma Jul 17, 2025

In this episode, Associate Editor Dr. Philippe Armand discusses the Review Series on mantle cell lymphoma with author Dr. Christine Ryan. Both were authors of "Frontline management of mantle cell lymphoma", and discuss shifts in treatments and new research.

Find the full review series in Volume 145 Issue 7 of Blood: "Review series on mantle cell lymphoma: sands shifting in the darkness"

Rapid, high-sensitivity ADAMTS13 assays for TTP; combination CD38/PD-1 blockade in extranodal NK/T-cell lymphoma; a “zombie enzyme” in CREBBP-mutant lymphomas Jul 10, 2025

In this week's episode, we'll learn about rapid, high-sensitivity diagnostic assays for TTP, or thrombotic thrombocytopenic purpura, that can reduce unnecessary treatments. After that: enhancing PD-1 blockade in relapsed/refractory extranodal NK/T-cell lymphoma. In a single-arm, phase 2 study, combined CD38 and PD-1 inhibition demonstrated durable responses and manageable safety. Finally, a lymphoma horror story with a happy ending. CREBBP mutations create a zombie enzyme that competes with its wild-type counterparts. By enforcing CD40 signaling, a bispecific antibody overcomes this effect and induces lymphoma cell death.

Featured Articles:

A novel mouse model of sickle cell SC disease; multiple myeloma induction therapy with isatuximab, carfilzomib, lenalidomide, and dexamethasone; and splicing factor mutations in myelodysplastic syndromes Jul 03, 2025

In this week's episode we’ll learn more about a novel mouse model that recapitulates many of the properties of human sickle cell SC disease; results from the induction phase of the risk-adapted MIDAS trial of isatuximab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed, transplant-eligible multiple myeloma; and a link between splicing factor mutations and competitive fitness in myelodysplastic syndrome stem cells.

Featured Articles:

Social determinants of health and access to allogeneic hematopoietic cell transplantation, megakaryocyte growth factor receptor-based pretransplant conditioning for ex vivo autologous gene therapy, and novel protein biomarkers for risk stratification in a Jun 23, 2025

In this week's episode, we’ll learn more about social determinants of health that impact access to allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia, or AML; use of megakaryocyte growth factor receptor-based stem cell depletion as part of pretransplant conditioning in ex vivo autologous gene therapy; and identification of an eight-protein risk signature as well as a novel single protein biomarker, soluble oncostatin M receptor, for risk stratification in AML.

Featured Articles:

Aggressive non-Hodgkin lymphoma: defining and managing high-risk subsets Jun 19, 2025

Blood editor Dr. Laurie Sehn discusses the topic of "Aggressive non-Hodgkin lymphoma: defining and managing high-risk subsets" featuring Drs. Mark Roschewski, Grzegorz Nowakowski, and Neha Mehta-Shah, who each contributed to the articles featured in the review series on high-risk aggressive lymphoma.

See the full review series on high risk lymphoma in volume 144, issue 25 of Blood.

A key role for T-cell TET3 in chronic GVHD; a BTK inhibitor for ITP; co-inhibition of pre-TCR and IL-7R pathways in a T-ALL patient subset Jun 12, 2025

In this week's episode, we' ll learn about how TET3 has a key role in GVHD. In mice, a deficiency of Tet3 in donor T cells inhibited pathogenic immunoglobulin class switching and suppressed lung fibrosis. Accordingly, TET3 may be a new therapeutic target in chronic GVHD. After that: rilzabrutinib, a BTK inhibitor for ITP. In a randomized, placebo-controlled trial, treatment produced rapid and durable platelet responses, with acceptable safety, in adults with immune thrombocytopenia who had failed multiple previous therapies. Finally: exploring pre-TCR surface expression patterns in T-cell ALL. Co-inhibition of the interleukin-7 receptor and pre-T cell receptor pathways may play a therapeutic role for a subset of T-lymphoblastic leukemias.

Featured Articles:

Special Episode: Eliminating the Need for Sequential Confirmation of Response in Multiple Myeloma Jun 10, 2025

In this special episode, Dr. Shaji Kumar from the Mayo Clinic speaks with Blood editor Dr. Laurie Sehn on a paper recently published in Blood, "Eliminating the Need for Sequential Confirmation of Response in Multiple Myeloma". The findings demonstrate eliminating the need for sequential confirmation of response in multiple myeloma. The study, involving 583 episodes of progression, found that simultaneous confirmation of disease progression using two different markers (e.g., serum protein electrophoresis and serum free light chain assay) was 98% accurate, compared to 82% for sequential confirmation. This suggests that simultaneous confirmation could improve clinical trial accuracy and reduce false censoring. The International Myeloma Working Group is set to revise its response criteria to incorporate these findings, potentially simplifying disease assessment and reducing the need for multiple blood draws.

How I Treat Series on Geriatric Hematology Jun 05, 2025

In this How I Treat Series episode Dr. Thomas Ortel leads a discussion with author Dr. Patrick Foy on his paper “How I diagnose and treat thrombocytopenia in geriatric patients”.
See the full How I Treat series on geriatric hematology in volume 143 issue 3 of Blood Journal.

Single cell multi-omic analysis of leukemia stem cells, cyclophosphamide for non-immune effector cell-associated neurotoxicity, and glycosylation as a mediator of von Willebrand factor clearance Jun 05, 2025

In this week's episode, we’ll learn more about the identification and characterization of stem cell-like leukemia blasts using single cell multi-omics, cyclophosphamide as a treatment for non-immune effector cell-associated neurotoxicity in patients treated with B-cell maturation antigen, or BCMA, targeted CAR T-cell therapies, and how differences in glycosylation affect the clearance of human plasma-derived and recombinant von Willebrand factor concentrates.

Featured Articles:

New insights on PU.1-mutated agammaglobulinemia; venetoclax-based induction therapy in younger AML patients; the link between ABO Blood groups and risk of future VTE May 29, 2025

In this week's episode, we'll hear about new insights into PU.1-mutated agammaglobulinemia. Researchers show that haploinsufficiency of the master transcriptional regulator PU.1 causes agammaglobulinemia and dendritic cell deficiencies. These patients experience an array of infectious and non-infectious complications, but not leukemia. After that: venetoclax-based induction therapy in younger patients with AML. Venetoclax plus decitabine was associated with superior safety and non-inferior response rates compared to intensive chemotherapy. Is it time to consider lower-intensity therapy beyond older and unfit patients? Finally, a focus on venous thromboembolism. Researchers link BGAT, an enzyme pivotal to determining blood type, to risk of future VTE. They say high plasma levels of BGAT contribute to risk above and beyond what can be explained by von Willebrand factor and Factor VIII.

Featured Articles:

How I Treat Transfusion Medicine (part 2) May 22, 2025

In part two of the How I Treat Series on Transfusion Medicine Dr. Erica Wood interviews the "How I Manage Major Hemorrhage" author group: Drs. Jeannie Callium, Keyvan Karkouti, and Ron George.

Find the full published review series in Volume 145 Issue 20 of Blood Journal.

Clonal hematopoiesis in frequent blood donors, immune microenvironment and bispecific antibody response in diffuse large B-cell lymphoma, and blinatumomab as part of early consolidation therapy in CD19-positive Ph-negative B-cell acute lymphoblastic lymphoma May 22, 2025

In this week's episode we’ll learn about how frequent blood donation affects clonal hematopoiesis in older, male blood donors; the effect of immune microenvironment on response to bispecific antibodies in diffuse large B-cell lymphoma; and the feasibility of adding blinatumomab to early consolidation therapy in CD19-positive Ph-negative B-cell acute lymphoblastic lymphoma.

Featured Articles

How I Treat Transfusion Medicine (part 1) May 15, 2025

In this two-part series, Dr. Erica Wood talks with Drs. Masja de Haas, Helen Savoia, and Stella Chou about their articles in the How I Treat Series on Transfusion Medicine. Topics include noninvasive prenatal testing for red blood cell and platelet antigens, transfusion cases in sickle cell disease, and pregnant patients who are alloimmunized to RBC antigens.

Find the full published review series in Volume 145 Issue 20 of Blood Journal.

Discontinuing lenalidomide maintenance in MM; congenital neutropenia syndrome linked to COPZ1 mutations; low GVHD rates with ruxolitinib after allogeneic HCT May 15, 2025

In this week's episode, we'll learn about stopping myeloma maintenance therapy in the modern era. New research suggests that many patients in remission can discontinue lenalidomide, remaining treatment-free, without jeopardizing disease response. After that: a novel congenital neutropenia syndrome. Mutations in the COPZ1 gene impact myeloid differentiation and development of neutropenia. Researchers describe the mechanisms and propose a treatment strategy for restoring granulopoiesis. Finally, ruxolitinib maintenance therapy after allogeneic transplant. In a phase 2 study, this treatment strategy was associated with low rates of chronic graft-versus-host disease. Investigators say the use of JAK inhibitors in this context warrants further study.

Featured Articles:

Measurable residual disease and maintenance therapy in acute myeloid leukemia (AML), stemness and chemotherapy resistance in AML, and effects of babesiosis on red blood cells in sickle cell disease May 08, 2025

In this week's episode, we’ll learn more about how measurable residual disease might help guide decisions about post-transplant gilteritinib maintenance in FLT3-ITD acute myeloid leukemia, or AML; how stemness contributes to chemotherapy resistance in AML; and effects of babesiosis on red blood cells from individuals with sickle cell disease, sickle cell trait, and wild-type hemoglobin.

Featured Articles:

Uniquely programmed blood stem cells in the human lung; inclusive molecular classifier for DLBCL; new insights on NETs in the liver vasculature May 01, 2025

In this week's episode, we'll hear about how researchers look toward the lung, and find uniquely programmed blood stem cells. This study is the first to fully characterize hematopoietic stem and progenitor cells in the adult human lung. After that: researchers develop a neural network-based probabilistic classifier, DLBclass, that assigns all diffuse large B-cell lymphomas into one of five genetic subtypes. It’s an inclusive taxonomy that they say provides actionable genetic information in almost all patients with DLBCL. Finally, new insights on NETS, or neutrophil extracellular traps. In the liver vasculature, NET removal leads to secondary inflammation, resulting in new waves of NETS that may impact future infection. We’ll review these and other findings from this recent mouse model study.

Featured Articles:

Phosphoseryl-tRNA kinase inhibition in acute myeloid leukemia (AML), APOE gene variants and post-hematopoietic stem cell transplant outcomes in AML, and the role of chronic inflammation in sickle cell cardiomyopathy Apr 24, 2025

In this week's episode we’ll learn more about how phosphoseryl-tRNA kinase inhibition promotes cell death in acute myeloid leukemia, or AML; APOE gene variants and their association with post-hematopoietic stem cell transplant outcomes in AML; and pathways by which chronic inflammation and oxidative stress may lead to cardiomyopathy in patients with sickle cell disease.

Featured Articles:

How I Treat Myeloproliferative Neoplasms Apr 17, 2025

In this How I Treat series episode Blood Associate Editor, Dr. Jason Gotlib speaks with Drs. Aaron Gerds, Andreas Reiter, and Claire Harrison. The conversation focuses on the work and contributions of these authors to How I Treat Myeloproliferative Neoplasms, and exciting advances in the treatment and management of MPNs.

See the full How I Treat series in volume 145 issue 16 of Blood.

The decline of transplant for relapsed myeloma; DDAVP response in bleeding disorders; dual DOT1L/EZH2 targeting in DLBCL Apr 17, 2025

In this week's episode we'll learn about the role of autologous transplant for relapsed myeloma. In an updated analysis of the GMMG ReLApsE trial, salvage autologous transplant offered no survival benefit compared to control chemotherapy. These findings may have clinical implications in an era of alternative, and highly effective, treatment options. After that: Response to DDAVP, or desmopressin, in bleeding disorders. This study is the first large scale meta-analysis to assess the response rate to DDAVP in bleeding disorders. Authors provide new insights into determinants of response, which vary according to the disease type. Finally, turning to diffuse large B cell lymphoma. Germinal center B cells depend on the activity of DOT1 and EZH2 to maintain their pro-proliferative identity. New research shows that combined treatment with DOT1L and EZH2 inhibitors has synergistic activity in vitro.

Featured Articles:

Interleukin-1 signaling pathways in myelodysplastic syndromes, the immune checkpoint regulator VISTA as a target in graft-vs-host disease, and epcoritamab plus chemotherapy in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma Apr 10, 2025

In this week's episode we’ll learn about the role of interleukin-1 signaling in the bone marrow microenvironment in the development of myelodysplastic syndromes, the immune checkpoint regulator VISTA as a potential target for preventing graft-vs-host disease, and epcoritamab plus gemcitabine and oxaliplatin in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma.

Featured Articles:

Aging platelets shift to proinflammatory function; Odronextamab bispecific antibody therapy after CAR T in DLBCL; prizlon-cel, a novel bispecific CAR T, in B-NHL Apr 03, 2025

In this week's episode we'll learn about tracking the functional profile of aging platelets. Researchers demonstrate that over time, platelet function shifts away from hemostasis and toward a more immunomodulatory role. These finding could have important implications for transfusion medicine and certain platelet-related disease states. After that, use of odronextamab, a CD20×CD3 bispecific antibody, in patients with diffuse large B-cell lymphoma, or DLBCL, progressing after CAR T cell therapy. The study is the first to evaluate the efficacy and safety of this therapy in the post-CAR T cell treatment setting. Finally, we will recap findings from a study of a novel CAR T-cell product that utilizes specificity to two antigens common in diffuse large B-cell lymphoma.

Featured Articles:

Blood Bonus Episode: What is a Blood group? Mar 31, 2025

In this bonus episode of the Blood podcast, we'll hear from Dr. Nicole Thornton, senior author of the article “Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype”, speaks with Blood Associate Editor Dr. Erica Wood about the discovery of the genetic basis for the inherited AnWj-negative blood group phenotype. The discovery that Mal protein is expressed on red blood cell membranes of AnWj-positive, but not AnWj-negative individuals, and that homozygous deletion in MAL causes the AnWj-negative blood group phenotype, helps answer a decades-old mystery related to the high prevalence red blood cell antigen AnWj and forms the basis of a new blood group system.

Itacitinib in haploidentical hematopoietic cell transplantation, diagnosis and management of purpura fulminans, and lack of evidence for sickle cell crisis-associated mortality in individuals with sickle cell trait Mar 27, 2025

In this week's episode, we’ll learn more about using itacitinib for the prevention of graft vs host disease in haploidentical transplants, diagnosis and management of purpura fulminans, and results of a systematic review seeking evidence for sickle cell crisis-associated mortality in individuals with sickle cell trait.

Featured Articles:

Time-limited triplet therapy in relapsed/refractory CLL; patient-reported outcomes in chronic GVHD-related sclerosis; myeloid bias mechanisms in hematopoiesis Mar 20, 2025

In today's episode, we'll discuss time-limited triplet therapy in relapsed or refractory CLL. Zanubrutinib, venetoclax and obinutuzumab induced deep remissions, and was well tolerated, even in very high-risk patients, and those with prior exposure to targeted therapies. After that: researchers chronicle the development of a patient-reported outcome measure for sclerosis associated with chronic GVHD—graft-versus-host disease. The new symptom scale—currently undergoing validation studies—may provide valuable information regarding severity, functional impact, and response to therapy. Finally, a study of changes in population dynamic rates that underlie inflammation-associated myeloid bias. The work demonstrates the use of mathematical models to deliver critical biological insights and uncover underlying mechanisms.

Featured Articles:

Azacitidine plus venetoclax in high-risk myelodysplastic syndromes, post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia (B-ALL), and inotuzumab ozogamicin resistance in B-ALL Mar 13, 2025

In this week's episode we’ll learn more about azacitidine-venetoclax combination therapy for first-line treatment of high-risk myelodysplastic syndromes; a new risk-scoring system for post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia, also known as B-ALL; and a novel mechanism for inotuzumab ozogamicin resistance in B-ALL.

Featured Articles:

Mutations in AMBRA1 aggravate β-thalassemia; targeting MYD88 mutations in lymphomas; air pollution and incident VTE risk Mar 06, 2025

In this week's podcast, a potential new therapeutic target in beta-thalassemia. The E3 ubiquitin ligase AMBRA1 promotes autophagic clearance of free alpha-globin. Researchers describe mutations in the AMBRA1 gene that impair this clearance, exacerbating ineffective erythropoiesis and disease severity. After that: targeting MYD88 mutations. Lasalocid-A is a compound that selectively binds to the MYD88 L265P mutant protein, which is found in a range of B-cell lymphomas. New research shows its potential to inhibit tumor growth, overcome ibrutinib resistance, and synergize with venetoclax. Finally: air pollution is linked to an increased risk of venous thromboembolism in a prospective, community-based cohort study. The findings highlight the harms of pollution, and support the case for global efforts to improve public health.

Featured Articles:

Hypercalcemia in monoclonal gammopathy of undetermined significance, neutrophil gelatinase-associated lipocalin in hemostasis, and CD19-targeted NK- or T-cell therapy combined with anti-CD19 monoclonal antibodies Feb 27, 2025

In this week's episode we’ll learn more about the significance of hypercalcemia in monoclonal gammopathy of undetermined significance, the role of neutrophil gelatinase-associated lipocalin in hemostasis, and the feasibility of combining CD19-targeted NK- or T-cell therapy with anti-CD19 monoclonal antibodies.

Featured Articles:

Review Series on a Quarter Century of TKIs in CML Feb 27, 2025

In this Review Series episode Reflections on a Quarter Century of TKIs in CML introduced by Associate Editor Dr. Jason Gottlieb, we’ll hear from contributing authors Drs. Brian Drucker, Francois Guillot, Tim Hughes and Michael Deininger, as they discuss how CML treatment has been impacted since the introduction of tyrosine kinase inhibitors 25 years ago.

Click here to view the complete Review Series featured in Volume 145 Issue 9 of Blood.

A “belt and suspenders” approach to PNH; oral pathogens exacerbate chronic GVHD; microbial metabolome changes may adversely impact CAR-T outcomes Feb 21, 2025

In this week's episode, we'll hear about a “belt and suspenders” approach to paroxysmal nocturnal hemoglobinuria, or PNH. We’ll review long-term efficacy data for danicopan—an oral complement factor D inhibitor recently approved as an add-on to C5 inhibitor therapy.
After that: researchers show how oral pathogens may exacerbate chronic graft-versus-host disease. And they assess targeted interventions to mitigate these effects. Finally, we move from the oral to the gut microbiome. New findings suggest that intestinal dysbiosis, induced by antibiotics, may adversely affect outcomes among patients who are receiving CAR-T cell therapy.

Featured Articles:

Mosunetuzumab in relapsed/refractory follicular lymphoma, CD70 CAR T-cells and an anti-CD33/anti-CD3 bispecific antibody in acute myeloid leukemia, and ferroptosis in stored red blood cells Feb 13, 2025

In this week's episode we’ll find out about longer term results from a pivotal trial of mosunetuzumab in relapsed/refractory follicular lymphoma, potential use of CD70 CAR T-cells that secrete an anti-CD33/anti-CD3 bispecific antibody as a therapy for acute myeloid leukemia, and how ferroptosis regulates hemolysis in stored red blood cells.

Featured Articles:

Review Series on Basic/Translational Science of Factor VIII, Factor IX, and von Willebrand Factor Feb 13, 2025

In this Review Series episode on Basic/Translational Science of Factor VIII, Factor IX, and von Willebrand Factor introduced by Dr. Thomas Ortel, we’ll hear from contributing authors Drs. Ben Samuelson Jones, Mac Monroe and Peter Lenting as they discuss how the functional roles of these 3 proteins are interconnected.

Click here to view the complete Review Series featured in Volume 144 Issue 21 of Blood.

Dual TKI targeting in Ph+ ALL; role of liver endothelial ferroportin in iron sensing and homeostasis; severe anemia in pregnant patients with beta-thalassemia minor Feb 06, 2025

In this week's episode we'll learn about asciminib plus dasatinib in Philadelphia chromosome-positive acute leukemia. In a phase 1 study, combining two tyrosine kinase inhibitors with distinct mechanisms of action had encouraging activity in patients with de novo disease. After that: new research demonstrates that the iron exporter ferroportin contributes to the iron-sensing properties of liver endothelial cells. But is it the primary mediator of systemic iron homeostasis? Finally: anemia in pregnant patients with beta-thalassemia minor. In the third trimester, about one-third of patients have hemoglobin levels of 9 grams per deciliter or lower. This report may help to guide the appropriate diagnosis of anemia while limiting unnecessary testing and interventions.

Featured Articles:

First-line zanubrutinib, obinutuzumab, and venetoclax in mantle cell lymphoma; hyperdiploidy in multiple myeloma; and pegcrisantaspase plus venetoclax in relapsed/refractory acute myeloid leukemia Jan 30, 2025

In this week's episode we’ll learn more about a phase 2 trial of first-line zanubrutinib, obinutuzumab, and venetoclax in TP53-mutated mantle cell lymphoma; early development of hyperdiploidy in multiple myeloma; and a phase 1 trial of the asparaginase pegcrisantaspase plus venetoclax in relapsed/refractory acute myeloid leukemia.

Featured Articles:

Targeting C3 in autoimmune hemolytic anemias; venetoclax testing to predict AML response; an improved understanding of the structure of FXIII complex Jan 23, 2025

In this week's episode we'll learn about C3-targeted therapy in autoimmune hemolytic anemias. Based on results of an open-label, phase 2 study, pegcetacoplan was well-tolerated, with encouraging efficacy, particularly in patients with cold agglutinin disease. After that: Venetoclax sensitivity testing to predict AML response. In a significant step toward precision medicine, researchers have validated an assay capable of predicting response to the venetoclax-azacitidine regimen. Finally, an improved basic understanding of human coagulation factor XIII. Investigators present the cryo-electron microscopy structure of Factor XIII complex, providing new insights into etiology and the deleterious effects of certain specific mutations.

Featured Articles:

Review Series on Globin Disorders Jan 23, 2025

In this Review Series episode on Globin Disorders introduced by Drs. Thomas Coates and Irene Roberts, we’ll hear from Dr. Douglas Higgs and Dr. Mitchell Weiss as they address advances in our understanding of globin gene biology.

Click here to view the complete Review Series featured in Volume 144 Issue 8 of Blood.

Brentuximab vedotin, nivolumab, and chemotherapy in classical Hodgkin lymphoma; type 1 interferon signaling in sickle cell disease; and type 1 human leukocyte antigen gene mutations in cutaneous T-cell lymphoma Jan 16, 2025

In this week's episode we’ll learn more about an experimental regimen for classical Hodgkin lymphoma that combines brentuximab vedotin, nivolumab, and chemotherapy; a possible role for type 1 interferon signaling in developing autoantibodies to red blood cells in sickle cell disease; and how genomic alterations affecting class I human leukocyte antigen molecules may affect patients with cutaneous T-cell lymphoma.

Featured Articles:

Iron overload aggravates MDS pathophysiology; long-term outcomes after TPO-RA treatment in ITP; new insights into APL treatment outcomes by age and risk Jan 09, 2025

In this week's episode we'll learn about the role of iron in myelodysplastic syndromes, or MDS. After that: long-term treatment outcomes in immune thrombocytopenia from the STOPAGO study. Finally, new insights into APL treatment outcomes and prognostic factors from the large-scale Harmony APL project which used ATRA-Arsenic combination therapy.

Featured Articles:

Dexamethasone dosing in newly diagnosed multiple myeloma, a new experimental model of X-linked sideroblastic anemia, and ciltacabtagene autoleucel in real-world myeloma treatment Jan 02, 2025

In this week's episode, we’ll learn about the prevalence and impact of dexamethasone dose reductions during triple or quadruple therapy for newly diagnosed multiple myeloma, a conditional knockout mouse model for testing gene therapy in X-linked sideroblastic anemia, and real-world efficacy and safety of ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma.

Featured Articles:

Comparing BTK inhibitors in relapsed/refractory CLL; unraveling the genetic background of the AnWj-negative blood type; rapid adaptation of CLL cells to venetoclax Dec 26, 2024

In this week's episode, we'll be comparing BTK inhibitors in relapsed/refractory CLL. Then, we'll hear how researchers in the UK unraveled the genetic background of the AnWj blood group. Finally we'll learn about the role of BCL-2 and BAFF in CLL cell survival following venetoclax therapy.

Featured Articles:

Primary resistance to BCMA-targeted bispecifics in multiple myeloma, emapalumab therapy in hemophagocytic lymphohistiocytosis, and chemotherapy-induced pyroptosis as a mechanism of thrombus formation in patients with cancer Dec 19, 2024

In this week's episode, we’ll learn more about mechanisms of primary resistance to BCMA-targeted bispecific T-cell engagers in relapsed/refractory multiple myeloma, the effects of emapalumab therapy on outcomes in patients with pediatric hemophagocytic lymphohistiocytosis who receive stem cell transplants, and a cell death process that may help account for increased thromboembolic risk in patients receiving cancer chemotherapy.

Featured Articles:

Unravelling follicular lymphoma subtypes; stroke rate trends in sickle cell disease; procoagulant platelet activation promotes venous thrombosis Dec 12, 2024

In this week's episode, unravelling follicular lymphoma subtypes. Researchers dissect the biological diversity of follicular lymphoma and introduce a new prognostic mode, that could change the way this B-cell neoplasm is subtyped and treated. Then, concerning stroke rate trends in sickle cell disease. A new report shows increasing rates of cerebrovascular events among people with SCD in California. Finally, procoagulant platelet activation promotes venous thrombosis. Investigators report finding procoagulant platelets in the circulation and in thrombi of patients and mice with DVT or PE.

Featured Articles:

Clonal hematopoiesis in patients with telomere biology disorders, genomic alterations in extracutaneous juvenile xanthogranulomas, and the BCMA-CD3 bispecific antibody teclistamab in relapsed/refractory multiple myeloma Dec 05, 2024

In this week's episode we’ll learn more about how clonal hematopoiesis affects prognosis in patients with telomere biology disorders, consider recently uncovered molecular subtypes of extracutaneous juvenile xanthogranulomas, and discuss a clinical trial of the BCMA-CD3 bispecific antibody teclistamab in patients with relapsed/refractory multiple myeloma who have received previous BCMA-targeted therapy.

Featured Articles:

Targeting mutant calreticulin in MPNs; focusing on bleeding risk in patients with cancer; revisiting diagnostic guidelines for familial HLH Nov 28, 2024

In this week's podcast, we'll learn about targeting mutant calreticulin in MPNs, or myeloproliferative neoplasms. Then, it’s time to address bleeding and clotting in cancer. Results of the prospective, observational CAT-BLED study provide much needed data on the high risk of clinically relevant bleeding, and its association with all-cause mortality, among cancer patients receiving systemic therapy. Finally, we'll revisit diagnostic guidelines for familial HLH, or hemophagocytic lymphohistiocytosis. The authors present new and improved diagnostic criteria with revised clinical criteria, and guidelines on cellular and genetic diagnostic assays.

Featured Articles:

Review Series on T-Cell Lymphoma Nov 21, 2024

In this Review Series episode on T-Cell Lymphomas introduced by Dr. Philippe Armand we’ll hear from Drs. Laurence de Leval, Javeed Iqbal, and Enrica Marchi about their work concerning new treatment practices and insights to various t-cell lymphomas.

Click here to view the complete Review Series featured in Volume 144 Issue 18 of Blood.

Stratifying risk in acute myeloid leukemia, daratumumab plus chemotherapy in relapsed-refractory pediatric leukemias, and a method for creating genetically engineered platelets Nov 21, 2024

In this week's episode we’ll learn more about a new risk classification scheme for use in patients with acute myeloid leukemia who are ineligible for intensive therapy, efficacy and safety of daratumumab plus chemotherapy in pediatric patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, and a blood bank-compatible method for creating genetically engineered platelets with a wide range of potential uses.

Featured Articles:

Exploring the ecosystem of extramedullary myeloma; role of ruxolitinib for pediatric acute GvHD; “YAP”-ing about YAP1 and thrombopoiesis in ITP Nov 14, 2024

In this week's episode we'll learn about new explorations in extramedullary myeloma. Then, we'll hear about the role of ruxolitinib in children with acute GvHD. Finally: yapping about YAP1 as a new treatment target in immune thrombocytopenia.

Featured Articles:

First-line asciminib for chronic myeloid leukemia, a new risk score for clonal cytopenia, and genotyped D-positive blood transfusion in sickle cell anemia Nov 07, 2024

In this week's episode we’ll learn more about the ASCEND study, which investigated first-line asciminib in chronic phase chronic myeloid leukemia; a new risk score for myeloid neoplasm transformation in patients with clonal cytopenia of undetermined significance; and use of RHD genotyped D-positive blood transfusions in patients with sickle cell and unexpected anti-D antibodies.

Featured Articles

Update on fixed-dose venetoclax-obinutuzumab in previously untreated CLL; dual epi-immunotherapy in cHL; predicting treatment failure in TKI-treated CML Oct 31, 2024

In this week's episode we'll learn about the updated phase 3 results on fixed-dose venetoclax plus obinutuzumab in previously untreated CLL. Then, we'll hear about dual epi-immunotherapy in classical Hodgkin lymphoma. Finally we'll explore redefining risk of treatment failure in CML.

Featured Articles:

Bone marrow failure related to ERG insufficiency, factor 11 in vascular hyperpermeability, and new criteria for evaluating anemia in myelofibrosis Oct 24, 2024

In this week's episode we’ll learn more about the role of ERG loss-of-function variants in bone marrow failure and hematological malignancies, a proposed pathway linking factor 11 activation to increased vascular permeability during inflammation, and new clinical criteria for diagnosing anemia, defining transfusion-dependence, and evaluating anemia treatment responses in patients with myelofibrosis.

Featured Articles:

Platelet glycoprotein receptor VI in abdominal aortic aneurysms, TP53 mutations in 5q-deleted myelodysplastic syndrome, and immunostimulatory cytokine plus CAR T-cell therapy in acute lymphoblastic leukemia Oct 17, 2024

In this week's episode, we'll learn about the role of a platelet-specific glycoprotein receptor in abdominal aortic aneurysm formation, the influence of TP53 mutations on outcomes for patients with 5q-deleted myelodysplastic syndrome, and a rational combination treatment intended to produce more durable responses in patients with refractory B-cell acute lymphoblastic leukemia who are treated with CAR T-cell therapy.

Featured Articles:

Using NGS to refine risk stratification in T-ALL; a novel gene therapy approach in severe α-thalassemia; molecular taxonomy of MDS Oct 10, 2024

In this week's episode we'll learn about refining risk stratification in T-cell acute lymphoblastic leukemia, or ALL. After that, we'll discuss a novel gene therapy approach in severe alpha-thalassemia. Investigators describe an innovative mouse model and an effective gene therapy approach, renewing prospects for the development of novel strategies to treat this disease. Finally, we'll hear about how genomic profiling has helped identify subgroups associated with distinct clinical phenotypes and outcomes in the molecular taxonomy of myelodysplastic syndromes, or MDS.

Featured Articles

A novel tripartite fusion drives treatment resistance in atypical APL; managing iTTP without TPE; hope for motherhood after allogeneic HCT Oct 03, 2024

In this week's episode we’ll discuss a novel tripartite fusion drives treatment resistance in acute promyelocytic leukemia. In some patients with atypical APL, these novel retinoic acid receptor gene fusions result in truncation of the ligand binding domain of the retinoic acid receptor protein, resulting in non-responsiveness to treatment with all-trans retinoic acid. After that: managing immune thrombotic thrombocytopenia or iTTP without therapeutic plasma exchange, or TPE. Finally, hope for motherhood after allogeneic HCT.

Featured Articles:

Pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL; murine models of erythroid 5ALA synthesis disorders; targeting PKCa in diabetes and hemochromatosis Sep 26, 2024

In this week's episode we’ll discuss the safety and efficacy of pirtobrutinib with or without rituximab in relapsed/refractory CLL; learn more about erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine; and discuss how targeting PKC alpha alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin.

Featured Articles:

Transplant outcomes in pediatric Fanconi anemia; hepatic Foxo1 regulates iron homeostasis; clinical networks improve APL outcomes in Latin America Sep 19, 2024

In this week's episode we'll discuss outcomes following hematopoietic stem cell transplantation in pediatric patients with Fanconi anemia. Then, we'll learn about how new research shows that the transcription factor Foxo1, commonly associated with glucose metabolism, regulates hepcidin expression and systemic iron homeostasis. Finally, in Latin America: using clinical networks to improve outcomes in patients with acute promyelocytic leukemia. After clinical networks were established, survival and relapse rates improved substantially, highlighting the effectiveness of this unique intervention strategy in low- and middle-income countries.

Featured Articles:

CD8+ T-cell differentiation and treatment response in AML; ATM germline pathogenic variants affect cancer outcomes in ataxia-telangiectasia; efficacy of a selective menin-KMT2A inhibitor in KMT2A- and NPM1-altered leukemias Sep 12, 2024

In this week's episode we’ll discuss how CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemia; learn more about the effect of ATM germline pathogenic variants on the outcomes in children with ataxia-telangiectasia and hematological malignancies; and discuss the preclinical efficacy of a potent, selective menin-KMT2A inhibitor JNJ-75276617 in KMT2A- and NPM1-altered leukemias.

Featured Articles:

TCR-T cells for post-HCT leukemia recurrence; platelets are the predominant source of procoagulant membranes in hemostasis; BR + R maintenance for MCL Sep 05, 2024

In this week's episode we'll discuss HA-1-targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation. Next, we'll learn about how 4D intravital imaging in mice reveals the key role of platelets as a source of procoagulant membranes in hemostasis. Finally, we'll hear about modifications to a common induction and maintenance treatment for treatment-naïve mantle-cell lymphoma.

Featured Articles

Outcomes of younger patients with mantle cell lymphoma; M-protein assessment during maintenance therapy in multiple myeloma; in vivo CAR T-cell generation using lentiviral vectors Aug 29, 2024

In this week's episode we’ll discuss the outcomes of younger patients with mantle cell lymphoma experiencing late relapse; learn more about mass spectrometry-based assessment of M-protein in peripheral blood during maintenance therapy in multiple myeloma and discuss in vivo CAR T-cell generation in non-human primates using lentiviral vectors.

Featured Articles:

Review Series on Factor XI Aug 29, 2024

Introduced by Associate Editor Dr. Thomas Ortel, this bonus episode discusses the Review Series on Factor XI, published in volume 143 issue 15 of Blood Journal. Dr. Ortel is joined by contributing authors Owen McCarty, PhD, Gili Kenet, MD, and David Gailani, MD.

Review Series Articles:

Protective role of neonatal CMV infection in B-ALL; GVHD targets organoid-forming bile duct stem cells; seven-year outcomes for venetoclax-ibrutinib therapy in MCL Aug 22, 2024

In this week's episode we'll learn how cytomegalovirus infection early in life depletes preleukemic cells in a mouse model of B-cell acute lymphoblastic leukemia. After that we'll discuss new research, where GVHD targets organoid-forming bile duct stem cells in a TGF-beta-dependent manner. Conversely, a TGF-beta inhibitor protects these stem cells against GVHD and mitigates biliary dysfunction. Finally, we'll hear about the seven-year outcomes for venetoclax-ibrutinib in relapsed or refractory mantle cell lymphoma. In addition to long-term survival benefits, researchers report durable treatment-free remissions and effective retreatment in patients with MRD-negative complete responses.

Featured Articles:

Iron, HFE haemochromatosis, and infections; bispecific antibodies improve CAR T-cell response; determinants of outcome in NPM1-mutated AML Aug 15, 2024

In this week's episode we'll learn about iron, HFE hemochromatosis, and infections. In this large, population-based study, both high and low levels of plasma iron and transferrin saturation were associated with increased risks of infection. Then, we'll discuss how bispecific antibodies improve CAR T-cell response in B-cell malignancies. In-vitro and in-vivo data demonstrate enhanced therapeutic efficacy when a CD20-directed bispecific antibody is given in combination with CD19-directed CAR-T cells. Finally, we'll hear about determinants of outcome in NPM1-mutated AML. In a large series of patients with NPM1-mutated AML, investigators identified several variables beyond FLT3-ITD that adversely impacted outcomes.

Featured Articles:

Immune fitness and response to taclistamab in R/R multiple myeloma; BCR::ABL1 M244V mutation causes resistance to asciminib; HSCT and myocardial fibrosis in young patients with SCD Aug 08, 2024

In this week's episode we’ll discuss how immune fitness impacts response to teclistamab in relapsed/refractory multiple myeloma; learn more about a new mechanism of resistance to asciminib conferred by the BCR::ABL1 M244V mutation, and discuss the impact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease.

Featured Articles:

Decitabine in older patients with AML; EPCR and sickle chronic kidney disease; lymphocyte depletion versus post-transplant cyclophosphamide for mismatched donor transplant for inborn errors of immunity Aug 01, 2024

In this week's episode we’ll discuss the safety and efficacy of decitabine in older patients with AML; learn how heme-induced loss of renovascular endothelial protein C receptor promotes chronic kidney disease in sickle mice, and discuss the outcomes of treatment with HLA-mismatched HSCT with TCRab/CD19 lymphocyte depletion or post-HSCT cyclophosphamide for inborn errors of immunity.

Featured Articles:

Impact of MRD-negative on PFS in myeloma; IPSS-R down-staging before transplant in MDS; hereditary angioedema and venous thromboembolism Jul 25, 2024

In this week's episode we'll discuss minimal residual disease as an intermediate clinical endpoint for multiple myeloma. Then, we'll learn about IPSS-R downstaging before transplant in MDS. Finally we'll hear about the connection between hereditary angioedema and venous thromboembolism.

Featured Articles:

Acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL; alternative donor transplantation for severe aplastic anemia; clonal relapse dynamics in AML following allogeneic HCT Jul 18, 2024

In this week's episode we’ll discuss the safety and efficacy of acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL; learn more about alternative donor transplantation for severe aplastic anemia and discuss clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation.

Featured Articles:

Clinical impact of CRh in AML; thrombosis features in a real-life PNH cohort; and restriction of SOX11 expression to EBV-negative Burkitt lymphomas Jul 11, 2024

In this week's episode we'll learn about the clinical benefit of complete remission with partial hematological recovery, or CRh, in patients with Acute Myeloid Leukemia (AML) treated with molecularly targeted drugs. Then we'll hear about a large cohort of patients with PNH were studied to detail PNH-related thrombotic events, unravel determinants of thrombosis, and evaluate anti-coagulation strategies. Finally, we'll see how new research shows that SOX11 expression is restricted to EBV-negative Burkitt lymphoma, and is associated with a specific genetic landscape.

Featured Articles:

Mutational and transcriptional landscape of pediatric BCP lymphoblastic lymphoma; the role of platelet-derived TGF-1 in immune thrombocytopenia; phase 3 trial of mavorixafor in WHIM syndrome Jul 04, 2024

In this week's episode we’ll discuss the mutational and transcriptional landscape of pediatric BCP lymphoblastic leukemia; learn more about the role of platelet-derived TGF-β1 in immune thrombocytopenia; and discuss the findings from a phase 3 trial of mavorixafor in WHIM syndrome.

Featured Articles:

Review Series on Oncogenic Signaling and Immune Evasion in Hematologic Malignancies Jun 27, 2024

Introduced by Associate Editor Robert Zeiser, this Review Series focuses on the problem of immune escape by acute myeloid leukemia (AML). The series opens with a review of how AML escapes T-cell–driven elimination and then focuses on how p53 function impinges on AML recognition by immune cells. The series finishes with a summary of new approaches to tackling this major problem.

Featured Series:

Introduction to a review series on oncogenic signaling and immune evasion in hematologic malignancies

GM-CSF coordinates shelter in the cytokine storm; Interleukin-1 as a therapeutic target in TTP; CAR T-cell outcomes across race and ethnicity in LBCL Jun 27, 2024

In this week's episode we'll discuss new insights on the role of GM-CSF in establishing immune memory. The authors propose that the coordination of opposing immune memory programs, driven by GM-CSF, may be essential to efficient, yet controlled, innate immune responses. After that: Interleukin-1 inhibition in TTP. Researchers explore the potential of recombinant IL-1 receptor antagonist, anakinra, in a murine model of thrombotic thrombocytopenic purpura—an uncommon but potentially fatal disorder with limited therapeutic options. Finally, we'll learn about CAR T-cell therapy outcomes by race and ethnicity in large B-cell lymphoma. Non-Hispanic Black patients had lower rates of response and progression-free survival in axi-cel clinical trials and real-world data, raising awareness and giving further insights into potential inequitable access to care.

Featured Articles:

Reassessing the CLL prognostic index; ADAMTS13 conformation and risk of relapse in immune-mediated TTP; haploidentical bone marrow transplant in sickle cell disease Jun 20, 2024

In this week's episode we’ll discuss the prognostic value of the Chronic Lymphocytic Leukemia International Prognostic Index in the era of targeted therapies, learn how peak ADAMTS13 activity can be used to assess ADAMTS13 conformation and risk of relapse in immune-mediated thrombotic thrombocytopenic purpura, and discuss the findings from a phase 2 trial of haploidentical bone marrow transplant in sickle cell disease.

Featured Articles

A biomarker for disease severity in Wiskott-Aldrich Syndrome; loss of Dnmt3a confers resistance to IFNα; unrelated donor selection in HSCT with PTCy Jun 13, 2024

In this week's episode we'll discuss assessing risk profile in Wiskott-Aldrich Syndrome, or WAS. Then, we'll learn about how the loss of DNMT3A confers resistance to interferon-alpha in hematopoietic stem cells carrying the JAK2-V617F mutation. Finally, we'll explore unrelated donor selection for AML patients undergoing hematopoietic stem cell transplantation with post-transplant cyclophosphamide.

Featured Articles:

Nilotinib with or without cytarabine for Philadelphia-positive AML; thrombosis risk in Factor V Leiden and Prothrombin G20210A; ctDNA improves prognostic prediction in relapsed/refractory multiple myeloma Jun 06, 2024

In this week's episode we’ll discuss the safety and efficacy of nilotinib with or without cytarabine in Philadelphia-positive acute lymphoblastic leukemia; learn more about thrombosis risk in double heterozygous carriers of Factor V Leiden and prothrombin G20210A and discuss the utility of circulating cell-free tumor DNA in prognostic prediction in patients with relapsed/refractory multiple myeloma.

Featured Articles:

Hemophilia prophylaxis with fitusiran vs BPA/CFC; germline NBN variants in pediatric B-ALL; Histone demethylation and cell-intrinsic immune response in AML May 30, 2024

In this week's episode we'll learn about fitusiran prophylaxis in patients with hemophilia A or B, with or without inhibitors. Next we'll hear about new findings that heterozygous germline variants in the NBN gene that are linked to increased risk of B-cell acute lymphoblastic leukemia in children. Finally, we'll explore new insights on the histone demethylase PHF8, which has been identified as a master regulator of cell-intrinsic immune responses in acute myeloid leukemia.

Featured Articles:

Effects of voxelotor on cerebral blood flow in pediatric sickle cell disease; thrombosis in Vexas syndrome; response to tyrosine kinase inhibitors in ABL-class acute lymphoblastic leukemia May 23, 2024

In this week's episode we’ll discuss the effects of voxelotor on cerebral blood flow in pediatric sickle cell disease, learn more about venous and arterial thrombosis in patients with Vexas syndrome, and discuss differential sensitivity to tyrosine kinase inhibitors in ABL-class acute lymphoblastic leukemia.

Featured Articles:

Stamping out high-risk myeloma with D-KRd and tandem transplant; plasmin-cleaved VWF in microthrombosis; SCD plasma sensitizes iPSC-derived sensory neurons May 16, 2024

In this week's podcast we'll discuss another step forward in stamping out high-risk myeloma. Then we'll hear about the plasmin-cleaved von Willebrand factor, or VWF, in microthrombosis. Finally we'll hear about new insights into the origins of sickle cell pain.

Featured Articles:

Allogeneic transplant in first remission for post-induction molecular MRD; circulating HSPCs actively participate in human hematopoiesis; let-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching May 09, 2024

In this week's episode we’ll discuss the utility of MRD in identifying patients with NPM1 AML who benefit from allogeneic transplant in first remission, learn more about the contribution of circulating hematopoietic stem/progenitor cell subsets to human hematopoietic hemostasis, and discuss the role of Let-7 miRNAs in regulation of BCL11A transcription and hemoglobin switching.

Featured Articles:

ADAMTS13 recovery in caplacizumab-treated TTP; inhibition of venetoclax-resistant BCL2 variants with sonrotoclax; genomic insights from Castleman disease in twins May 02, 2024

In this week's epside we'll learn about ADAMTS recovery after caplacizumab therapy in patients with immune thrombotic thrombocytopenic purpura. Then, we'll hear about preclinical characterization of sonrotoclax, a potential second-generation BCL2 inhibitor. Finally we'll hear about new insights into the etiology of Castleman disease where researchers describe the unusual occurrence of idiopathic multicentric Castleman disease in identical twins.

Featured Articles:

Durable response after tisa-cel in adults with relapsed/refractory follicular lymphoma; high microRNA-145 plasma levels indicate decreased risk of VTE; epigenetic/immunogenetic signature in the prediction of outcomes for high-count monoclonal B lymphocytosis Apr 25, 2024

In this week's episode, we’ll discuss the findings from a study assessing responses after treatment with tisagenlecleucel [LM1] in adults with relapsed/refractory follicular lymphoma, learn more about the association between high microRNA-145 plasma levels and decreased risk of future incident venous thromboembolism, and discuss how epigenetic and immunogenetic signatures can be used in the prediction of outcomes for high-count monoclonal B lymphocytosis.

Featured Articles:

Gut microbiota exploitation by CPX-351 in AML; optimizing anti-myeloma immunity for ASCT; which pediatric ITP patients will develop lupus? Apr 18, 2024

In this week's episode, we'll discuss gut microbiota exploitation by CPX-351 in acute myeloid leukemia. Then we'll learn about optimizing anti-myeloma immunity. New research shows that regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation. Finally we'll discuss among pediatric patients with ITP or other autoimmune cytopenias, which ones will go on to develop systemic lupus?

Featured Articles:

Jak2V617F clonal hematopoiesis promotes arterial thrombosis; Staphylococcus aureus infection in Sézary syndrome; clinical features of RAC2-related immunodeficiency Apr 13, 2024

In this week's episode we’ll discuss the mechanism by which Jak2V617F clonal hematopoiesis promotes arterial thrombosis, discuss how Staphylococcus aureus induces drug resistance in cancer T cells in Sézary syndrome, and learn more about the clinical and functional features of RAC2-related immunodeficiency.

Featured Articles:

Molecular mimicry in aplastic anemia; emicizumab prophylaxis in infants with hemophilia; hydroxyurea reduces infections in SCA Apr 04, 2024

In this week's episode we'll discuss molecular mimicry in aplastic anemia, novel experiments show that antigens associated with viral infections can mimic epitopes presented on hematopoietic progenitor cells. Then, we'll learn about prophylaxis with subcutaneous emicizumab in infants with hemophilia. Finally we'll see how hydroxyurea is associated with a significant reduction in infections among children with sickle cell anemia in Uganda.

Articles featured this week:

Review Series on the Influence of the Tumor Microenvironment on the Pathogenesis of B-Cell Lymphomas Mar 28, 2024

In this bonus episode of Blood Podcast, Associate Editor, Dr. Freda Stevenson is joined by Drs. Karin Tarte, Andrea Radtke, and Leandro Cerchietti to discuss the Review Series on the influence of the tumor microenvironment on the pathogenesis of B-cell lymphomas.

Find the full review series in Blood Journal volume 143 issue 12.

Free light chain mass spectrometry in diagnosis and monitoring of AL amyloidosis; T cells of AML patients in remission have distinct RNA signatures; and protective effect of ADAMTS13 in sickle cell mice depends on von Willebrand factor clearance Mar 28, 2024

In this week's episode we’ll discuss the findings from a study assessing the utility of free light chain mass spectrometry in AL amyloidosis, learn more about distinct single-cell RNA-sequencing signatures of bone marrow T cells of AML patients in remission after an allogeneic stem cell transplant, and discuss why von Willebrand factor clearance is critical for the protective effect of ADAMTS13 in mice with sickle cell anemia.

Articles featured in this episode:

Eculizumab in transplant-associated thrombotic microangiopathy; reclassifying malignant monocytosis; targeting tissue factor in antiphospholipid syndrome Mar 21, 2024

In this week's episode we'll discuss eculizumab in stem cell transplant-associated thrombotic microangiopathy. Then, we'll learn about reclassifying malignant monocytosis, these newly classified cases have distinct mutational and transcriptional profiles. Finally, we'll hear about targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development.

Articles featured in this episode:

Identification of rare relapse-initiating stem cells post-transplantation; interferon α impairs erythropoiesis in sickle cell disease; TNFα promotes clonal dominance of KIT D816V+ cells in mastocytosis Mar 14, 2024

In this week's episode we’ll learn more about rare relapse-initiating stem cells in patients with MDS or AML in complete remission post-transplantation, discuss the role of interferon α in erythropoiesis in sickle cell disease, and learn more about how TNFα promotes clonal dominance of KIT D816V+ cells in mastocytosis.

How PAR2 signaling drives thrombo-inflammation; pretransfusion hemoglobin levels linked to survival in beta-thalassemia; etoposide is better than its reputation in primary HLH Mar 07, 2024

In this week's episode we'll discuss PAR2-biased signaling in thrombo-inflammation. Then, we'll learn about how hemoglobin levels are linked to survival in transfusion-dependent beta-thalassemia. Finally we'll hear about how etoposide is better than its reputation in primary HLH—hemophagocytic lymphohistiocytosis. Symptomatic patients treated with etoposide have substantially better outcomes as compared to the historical experience.

Brentuximab vedotin plus dacarbazine or nivolumab in classical Hodgkin lymphoma; loss of CD20 causes resistance to mosunetuzumab in r/r B-cell lymphomas; trogocytosis as a driver of RBC antigen loss Feb 29, 2024

In this week's episode we’ll discuss the findings from a prospective trial of brentuximab vedotin with dacarbazine or nivolumab in older patients with classical Hodgkin lymphoma, learn more about CD20 antigen loss as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas, and discuss the role of trogocytosis in red blood cell antigen loss.

CAR T cells plus ibrutinib in relapsed/refractory MCL; targeting SGF29 in AML; diffusion-limited oxygen release from stored blood Feb 22, 2024

In this week's episode we'll discuss CAR T cells plus ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma. Next, we'll learn about a new SAGA for acute myeloid leukemia. Finally, we'll hear about new evidence that oxygen delivery to tissues can become diffusion-limited during perfusion with stored blood.

Long-term outcomes of pulmonary embolism in children and adolescents; hereditary angioedema caused by a methionine-379 to lysine substitution in kininogens; predictors of loss of MRD negativity in multiple myeloma Feb 15, 2024

In this week's episode we’ll report on the findings from a study evaluating the long-term outcomes of pulmonary embolism in children and adolescents, discuss a new mechanism for hereditary angioedema caused by a methionine-379 to lysine substitution in kininogens, and learn more about predictors of unsustained minimal residual disease negativity in multiple myeloma patients.

Extended follow-up of axi-cel in indolent NHL; platelets help clear senescent RBCs; novel risk stratification strategy for CNS lymphoma Feb 08, 2024

In this week's episode we'll discuss extended follow-up from the ZUMA-5 trial of axicabtagene ciloleucel, or axi-cel. Then we'll learn about the role of platelets in binding and clearing senescent red blood cells. Finally, we'll hear about a new risk stratification strategy for lymphomas of the central nervous system, or CNS.

Lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma; reciprocal stabilization of coagulation factor XIII-A and -B subunits; inotuzumab ozogamicin for MRD in ALL Feb 01, 2024

In this week's episode we’ll discuss the findings from a two-year follow-up study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma, learn more about how reciprocal stabilization of coagulation factor XIII-A and -B subunits influences plasma FXIII concentration, and discuss the findings from a phase 2 study of inotuzumab ozogamicin for measurable residual disease in acute lymphoblastic leukemia in remission.

Maternal anticancer drug exposure and leukemia; PIEZO1-TMEM16F coupling in hereditary xerocytosis; NPM1 MRD during venetoclax therapy in NPM1-mutated AML Jan 25, 2024

In this week’s episode, we’ll discuss the association between occupational exposure to anticancer agents in a parent and subsequent cancer in a child. Then we’ll learn about deciphering and disrupting the activation of PIEZO1 in hereditary xerocytosis. Finally, we’ll hear about the assessment of measurable residual disease, or MRD, in patients with NPM1-mutated AML, or acute myeloid leukemia, receiving venetoclax-based NON-intensive therapy.

TCRαβ/CD19-cell depleted haploHSCT for pediatric leukemia; malignancy-associated hemophagocytic lymphohistiocytosis in Sweden; the bone marrow as the primary site of thrombopoiesis Jan 18, 2024

In this week's episode we’ll discuss the findings from a prospective trial of TCRαβ/CD19-cell depleted HLA-haploidentical transplantation to treat pediatric acute leukemia, learn more about the incidence, clinical characteristics, and survival of malignancy-associated hemophagocytic lymphohistiocytosis in Sweden, and discuss the bone marrow as the primary site of thrombopoiesis.

Fibrin polymerization and thrombosis; preventing CD19-negative relapse after CAR T-cell therapy in ALL; and impact of aberrant FUS condensates on HSC aging Jan 11, 2024

In this week's episode we’ll explore the role of fibrinogen polymerization in thrombosis. Then, we’ll discuss preventing CD19-negative relapse after CAR T-cell therapy in acute lymphoblastic leukemia. Finally, we’ll learn how increased levels of the RNA-binding protein FUS has been identified as an effector of hematopoietic stem cell aging.

CD24Fc for prevention of GVHD; origins of active EBV disease; the role of PF4 in platelet activation Jan 04, 2024

In this week's episode we’ll discuss the findings from a phase 2 study of CD24Fc for prevention of graft-versus-host disease, learn more about the origins of chronic active Epstein-Barr virus disease, and discuss the role of PF4 in platelet activation.

Profiling a new VITT-like disorder; real-world outcomes of tafasitamab and lenalidomide in LBCL; and spatial mapping of human hematopoiesis Dec 28, 2023

In this week's episode we'll uncover the clinical and pathological profile of a new disorder similar to VITT, or vaccine-induced thrombocytopenia and thrombosis. Then, we'll discuss real-world outcomes in patients with large B-cell lymphoma treated with tafasitamab and lenalidomide. Finally we'll learn about how advances in technology help unravel the spatial biology of bone marrow.

A natural history of familial platelet disorder with myeloid malignancy; HEXIM1 as an essential transcription regulator in erythropoiesis; residual disease predicts relapse in CML patients Dec 21, 2023

In this week's episode we’ll discuss the findings from a natural history study of patients with familial platelet disorder with myeloid malignancy, learn more about the role of HEXIM1 as an essential transcription regulator in human erythropoiesis, and discuss the utility of residual disease as a predictor of relapse in CML patients stopping TKI therapy.

ETP and MRD for risk assessment in T-ALL; allogeneic HCT outcomes in CGD; effects of pathogenic/likely pathogenic variants in inherited hemostasis disorders Dec 14, 2023

On today's episode we’ll discuss the prognostic significance of the ETP phenotype in children with T-cell ALL, address knowledge gaps in the management of chronic granulomatous disease and learn about the effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders.

Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML; inhibition of PLK4 in TP53-mutated AML; the role of CD44 in Plasmodium falciparum infection Dec 07, 2023

On today's episode we’ll discuss the findings from a phase 2 study of sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML, learn more about the inhibition of PLK4 in TP53-mutated AML, and discuss the role of CD44 in Plasmodium falciparum infection.

High-risk cytogenetics in solitary bone plasmacytomas; complement activation in vaso-occlusive pain episodes; platelet reactivity to predict thrombotic disease risk Nov 30, 2023

On today’s podcast we'll discuss high-risk cytogenetic abnormalities in solitary bone plasmacytomas. Then, we'll consider complement activation in vaso-occlusive pain episodes and how targeting C5a generation inhibited those effects. Finally we'll explore the genetics of platelet reactivity and how researchers used this data to develop a genetic score that was associated with risk of thrombotic diseases.

Very long-term follow-up of FCR therapy for CLL, risk assessment of KMT2A-rearranged B-cell precursor ALL in adults; anti-myeloma therapy using antibodies armed with B-BiTEs Nov 23, 2023

On this week's episode we’ll discuss the findings from a long-term follow up study of fludarabine, cyclophosphamide, and rituximab in IGHV-mutated CLL, learn more about the impact of genetic alterations and minimal residual disease in adults with KMT2A-rearranged B-cell precursor ALL, and discuss a pre-clinical study of reinforced immunotherapy for myeloma using a new bispecific antibody-based approach.

Fractionated gemtuzumab ozagamicin Dosing in Elderly AML Patients; Loss-of-function of ENT3 drives histiocytosis; Alternative splicing of CD20 5’-UTR in B-lymphomas Nov 16, 2023

In this week's episode we'll discuss if fractionated dosing of gemtuzumab ozogamicin provide additional benefit over a single dose in older adults with AML. Then, we'll consider how the loss-of-function of ENT3 drives histiocytosis. Researchers describe a novel pathway leading to histiocytosis that involves hyperactivation of TLR-MAPKinase signaling. This suggests a potential benefit of MAPKinase -directed targeted therapy in a range of histocytoses. Finally we'll discuss unraveling resistance mechanisms to anti-CD20 treatments in B-cell malignancies. Through alternative splicing, the MS4A1 gene encoding human CD20 generates multiple mRNA isoforms with distinct 5’ untranslated regions.

Review Series on RNA Therapeutics in Hematology Nov 14, 2023

In this bonus episode of Blood Podcast, Coordinating Editor, Dr. Jason Gotlib is joined by Drs. Sioban Keel, Margaret Ragni, and Andoni Echaniz-Laguna to discuss the Review Series on RNA Therapeutics in Hematology. The series highlights areas in which RNA therapeutics are most advanced: acute hepatic porphyria, transthyretin amyloidosis, and hemophilia.

Review Series on RNA Therapeutics in Hematology

Prognostic significance of splicing factor gene mutations in AML; therapy resistance in multiple myeloma; the effects of KIT ligand deletion on HSC homeostasis Nov 09, 2023

In this week's episode we’ll discuss the prognostic significance of splicing factor gene mutations in newly diagnosed AML, learn more about the findings from a multi-omics study of therapy resistance in multiple myeloma, and discuss the effects of KIT ligand deletion on systemic KIT levels and hematopoietic stem cell homeostasis.

Targeting prostacyclin to inhibit platelet activation; MRD-tailored myeloma maintenance; AREG and HSC function in DNA damage repair deficiency and aging Nov 02, 2023

In this week's episode we'll see how targeting the prostacyclin receptor is a promising strategy for regulating hemostasis and thrombosis. Then, we'll learn how new evidence indicates that the progression rate is low in MRD-negative myeloma patients who discontinue post-transplant lenalidomide and dexamethasone maintenance therapy after 2 years. Finally we'll discuss how amphiregulin from leptin receptor-positive niche cells in the bone marrow mediates crosstalk between the niche and hematopoietic stem cells under conditions of DNA repair deficiency and aging.

Lenalinomide plus rituximab for elderly patients with DLBCL, platelet GP6-mediated neutrophil recruitment in acute lung injury, and the role of AXL3 in mantle cell lymphoma. Oct 26, 2023

In this week's episode, we discuss the findings from a phase 2 study of lenalinomide plus rituximab in elderly frail patients with DLBCL, learn more about platelet GP6-mediated neutrophil recruitment in early stages of acute lung injury, and discuss a newly identified isoform of the tyrosine kinase AXL, termed AXL3, in mantle cell lymphoma.

Gut microbiota diversity and mortality in pediatric allo-HSCT; C5 inhibition in atypical HUS; and pembrolizumab plus vorinostat in PD-1-refractory Hodgkin lymphoma Oct 19, 2023

In this week's episode, we'll learn how the diversity of gut microbiota predicts mortality and acute graft-versus-host disease in pediatric allogeneic transplant recipients. Then we'll discuss complement inhibition in patients with complement-mediated atypical hemolytic uremic syndrome. Finally we'll learn how PD-1 plus HDAC equals responses in previously treated Hodgkin lymphoma, specifically that response rates were encouraging in a heavily pretreated cohort, even among patients with PD-1 refractory disease.

IL-15 inhibitor BNZ-1 is safe and effective in T-cell LGLL, gene therapy trial for Wiskott-Aldrich syndrome, and ethical framework to select patients for CAR T-cell therapy Oct 12, 2023

In this week's episode, we’ll discuss a phase two trial in patients with T-cell large granular lymphocytic leukemia treated with the inhibitor BNZ-1 to block receptor binding of IL-15, learn more about the outcomes of gene therapy for Wiskott-Aldrich syndrome, and discuss ways to mitigate inequity when prioritizing patients for CAR T-cell therapy.

DDX41 gene variant prevalence and AML/MDS risk, VITAL mAb treatment of light chain amyloidosis, and movement/neurocognitive toxicities after BCMA CAR T cell treatment Oct 05, 2023

In this week’s episode, we’ll learn that Germline pathogenic variants of the DDX41 gene are relatively common in the general population and linked to higher risk of AML and MDS, discuss the birtamimab plus standard of care in light chain amyloidosis, and review new insights on rare movement and neurocognitive toxicities that are observed after BCMA-directed CAR T cell treatment.

IL-7 receptor signaling in B-cell differentiation, venetoclax plus obinutuzumab in older patients with CLL, LDL promotes microvascular thrombosis via von Willebrand Factor Sep 28, 2023

In this weeks episode, we’ll learn more about the role of IL-7 receptor signaling in the differentiation and expansion of human B-cell progenitors, discuss the use of fixed-duration venetoclax plus obinutuzumab in older patients with chronic lymphocytic leukemia, and learn how low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand Factor self-association

Real-world CAR T therapy in older DLBCL patients, monoclonal antibody blocking APC for hemophilia therapy, and targeting the epichaperome in AML Sep 21, 2023

In this week’s episode, we discuss real-world evidence for CAR T cell therapy in older patients with diffuse large B-cell lymphoma, inhibiting endogenous anticoagulant pathways in congenital factor deficiencies, and finally targeting the HSP90 epichaperome in acute myeloid leukemia.

Obinutuzumab, ibrutinib, and venetoclax in untreated CLL with deletion(17p)/TP53 mutation; NOTCH2 mutants promote chemo-resistance in DLBCL; and the role of DBY/HLA class II complexes in chronic GVHD Sep 14, 2023

In this week's episode, we'll discuss the findings from the final analysis of the CLL2-GIVe trial, learn how NOTCH2 mutants promote resistance to chemotherapy in diffuse large B-cell lymphoma, and discuss the role of DBY/HLA class IIcomplexesin chronic graft-versus-host disease.

Long-term outcomes with pembrolizumab in Hodgkin lymphoma, the “incredible ULK” alleviates β-thalassemia, and recommendations for managing CAR T hematotoxicity Sep 07, 2023

In this week's episode, we’ll learn about long-term outcomes with pembrolizumab in relapsed/refractory classical Hodgkin lymphoma. Next, what’s behind the accumulation of toxic free alpha-globin in beta-thalassemia? Finally, a road map for managing CAR T cell hematologic toxicity.

How I Manage Inpatient Consultations for Quantitative Neutrophil Abnormalities in Adults Aug 31, 2023

Blood associate editors Jeanne Hendrickson and Thomas Ortel edited a How I Treat series on inpatient consultative hematology. In this timely series of articles, the authors present an approach to bleeding, thrombosis, anemia, and quantitative neutrophil abnormalities.

Dimethyl fumarate in cutaneous T-cell lymphoma, lipid nanoparticles for editing of human hematopoietic cells, and racial and geographic disparities in lymphoma trials Aug 31, 2023

In this week's episode, we’ll learn more about the treatment of relapsed and refractory cutaneous T-cell lymphoma with dimethyl fumarate, discuss the use of lipid nanoparticles for ex vivo editing of human hematopoietic cells, and learn more about racial and geographic disparities in lymphoma clinical trials.

Detailed safety profile of acalabrutinib vs ibrutinib in CLL, inflammation in trauma-induced coagulopathy, abatacept exposure and acute GVHD risk Aug 24, 2023

In this week’s episode, we’ll review a detailed safety profile of acalabrutinib versus ibrutinib in patients with previously treated chronic lymphocytic leukemia, discuss a report that leukocyte inflammation contributes to trauma-induced coagulopathy by oxidation and degradation of fibrinogen, and finally, discuss a pharmacokinetic-pharmacodynamic analysis that shows higher abatacept exposure decreases occurrence of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor.

Pembrolizumab after ASCT in PTCL, germline predisposition to myeloid neoplasms in patients with hypoplastic bone marrow, and limited plasticity of monocyte fate and function Aug 17, 2023

In this week’s episode, we’ll discuss pembrolizumab after autologous stem cell transplantation in patients with peripheral T-cell lymphoma. Newly reported phase 2 study results show that blocking PD-1 with pembrolizumab had a favorable safety profile and demonstrated promising activity, supporting further confirmatory studies in this setting; germline genetic predisposition to myeloid neoplasms in patients with hypoplastic bone marrow. Researchers report mutations that are significantly associated with cytopenias in adulthood in these patients. And pathogenic or likely pathogenic variants were linked to severe cytopenias and advanced myeloid malignancies; and finally, if monocytes and their descendants are less plastic than previously thought. Investigators have identified four functionally specialized monocyte subsets that derive from specific myeloid progenitor lineages. They show that the fate of these monocyte subsets is epigenetically scripted, with little flexibility after differentiation begins, even under conditions of stress.

Review Series on Hematopoietic Stem Cells Aug 10, 2023

In this week’s bonus episode of Blood Podcast, Associate Editor, Dr. John Crispino discusses the Review Series on Hematopoietic Stem Cells with authors, Dr. David Kent and Dr. Jennifer Trowbridge.

Review Series on Hematopoietic Stem Cells

WGS informs risk of follicular lymphoma transformation; resolvin D4 regulates neutrophil deployment; Hodgkin lymphoma-directed treatment for early-stage NLPHL Aug 10, 2023

In this week's episode, we’ll learn more about what whole genome sequencing reveals about genetic subtypes of follicular lymphoma and risk of transformation, discuss the role of the lipid mediator, resolvin D4, in infectious neutrophil deployment and emergency granulopoiesis, and learn more about Hodgkin lymphoma-directed therapy and the role of PET in early-stage nodular lymphocyte-predominant Hodgkin lymphoma.

Ventricular arrhythmias in sickle cell anemia, molecular heterogeneity of pediatric lymphoproliferative disorders, the role of the bone marrow microenvironment in myeloid disorders Aug 03, 2023

In this week's episode, we'll learn more about ventricular arrhythmias in sickle cell anemia, discuss the molecular heterogeneity of pediatric monomorphic post–solid organ transplant lymphoproliferative disorders, and uncover the role of the bone marrow microenvironment as a driver of myeloid disorders.

Silent infarcts in iTTP remission, a ZDHHC palmitoyltransferase regulates oxidative phosphorylation in AML, and hepatic sinusoid as a niche for ANKL Jul 27, 2023

In this week’s episode, we discuss the impact of silent cerebral infarction in patients with immune mediated thrombotic thrombocytopenic purpura (or iTTP) in clinical remission, how the survival of leukemia stem cells is highly dependent on oxidative phosphorylation in the mitochondria, and targeting iron import as a potential therapeutic approach in aggressive natural killer cell leukemia (or ANKL).

Poverty and relapse risk in children with ALL, eligibility and enrollment of diverse populations in myeloma trials, and clonal hematopoiesis in VEXAS syndrome Jul 20, 2023

In this week's episode, we’ll learn more about poverty and relapse risk in children with ALL, discuss eligibility criteria and enrollment of diverse racial and ethnic populations in multiple myeloma clinical trials, and learn more about clonal hematopoiesis in VEXAS syndrome.

Pembrolizumab in PMBCL, allogeneic CD19 CAR T cells for pediatric B-cell ALL, and fetal iron overload in β-thalassemia Jul 13, 2023

In this week's episode, we'll discuss if some patients with relapsed or refractory primary mediastinal B-cell lymphoma can be cured by checkpoint blockade alone. Next, autologous CAR T cells are highly effective, yet not always feasible in children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Lastly, we'll discuss ironing out beta-thalassemia during pregnancy.

Gene therapy for WHIM syndrome, fate of hematopoietic stem cells after transplantation, and the role of C-terminal FGF23 peptides in iron conservation Jul 06, 2023

In this week's episode, we’ll discuss the findings from a study attempting gene therapy for WHIM syndrome for the first time, learn more about the fate of hematopoietic stem cells after transplantation, and discuss the role of C-terminal FGF23 peptides in iron conservation.

Key role of hepcidin in polycythemia vera, signatures of CAR T cell dysfunction, and IL-34 as a novel AML therapy? Jun 29, 2023

In this week's episode, we'll discuss new evidence on the critical role of hepcidin, the master regulator of iron metabolism, in the pathogenesis of polycythemia vera. Next, costimulatory molecules regulate mechanisms of CAR T cell dysfunction. Finally, we'll discuss how TREM2 is a novel receptor for IL-34, promoting differentiation of normal and leukemic myeloid cells.

BMT as initial treatment for severe aplastic anemia, macrophage metabolic rewiring in sickle cell disease, and predicting outcomes using PET radiomics in diffuse large B cell lymphoma Jun 22, 2023

In this week’s episode we’ll report on the findings from a phase 2 trial of bone marrow transplantation as initial therapy for patients with severe aplastic anemia, discuss the utility of a PET radiomics-based model in predicting outcomes in diffuse large B-cell lymphoma, and learn more about macrophage metabolic rewiring in sickle cell disease.

End of the vincristine/steroid pulse era in pediatric ALL?, “trial and error” with abatacept in GVHD, and hemorrhage risk with dasatinib therapy Jun 15, 2023

In this week’s episode we will review no survival benefit for vincristine/steroid pulses in contemporary studies of childhood acute lymphoblastic leukemia (or ALL). Next, the rheumatology drug abatacept may be a promising strategy for the treatment of acute graft-versus-host disease (or GVHD). Finally, we'll discuss the hemorrhage risk of dasatinib therapy.

Prolonged response after stopping TPO-RA in ITP, TP53 mutations and myelofibrosis outcomes, clinical picture of ERCC6L2 disease, where variants predispose to marrow failure and malignancy Jun 08, 2023

Hodgkin lymphoma outcomes in the novel agent era, genomic safe harbors for precision T cell engineering, and a transcriptomic atlas to map imatinib resistance in CML Jun 01, 2023

In this week’s episode, we'll discuss how patients with relapsed or refractory Hodgkin lymphoma survival outcomes have improved after development of several novel agents. Next, precision engineering of therapeutic T cells through extragenic safe harbors. Finally, using a single-cell atlas to map features of imatinib resistance in diagnostic CML bone marrow, investigators present gene expression signatures predictive of response to TKI therapy.

Pembrolizumab plus AVD for classical Hodgkin lymphoma, targeting the CD40/CD40-ligand axis in Waldenström Macroglobulinemia, and CXCR4-expressing CAR-cytokine induced killer cells in AML May 25, 2023

In this week’s episode we’ll discuss the findings from a study exploring the combination of concurrent pembrolizumab, adriamycin, vinblastine, and dacarbazine in newly diagnosed classical Hodgkin lymphoma, learn more about the effects of targeting the CD40/CD40-ligand axis in Waldenström Macroglobulinemia, and review the findings from a study aimed at improving the bone marrow homing of CAR-cytokine induced killer cells in AML.

How I Treat Series: Emergent CAR T-Cell Toxicities May 18, 2023

In this bonus episode, Associate Editor, Dr. Helen Heslop discusses the How I Treat series on Emergent CAR-T cell toxicities with authors Dr. Fabiana Perna, Dr. Natalie Grover and Dr. Nirali Shah.

Specific CD8+ T cell clones in ITP, Refining DLBCL prognosis with the “dark-zone signature”, and rethinking the regenerative role of HSCs in acute hematopoietic emergencies May 18, 2023

In this week’s episode, we will review patients with chronic ITP having clonal expansions of a specific subset of CD8 T cells, called terminally differentiated effector memory T cells, or TEMRA. Next, for patients with diffuse large B-cell lymphomas, use of a so-called dark-zone signature, previously referred to as the double-hit signature, could help refine prognosis. Finally on today's podcast we'll discuss rethinking the role of hematopoietic stem cells following physiologic emergencies such as acute inflammation and blood loss.

Tips for Trainees for a Career in Publishing with Drs. Nancy Berliner and Andrew Roberts May 15, 2023

In this special episode, Trainee Council Chairs, Drs. Becky Zon and Ajay Major, interview Dr. Nancy Berliner, Blood Editor-in Chief and Dr. Andrew Roberts, Blood Deputy Editor, on their careers in academic editing and publishing, including career development tips for trainees who are interested in a career in publishing.

Axi-cel in refractory large B-cell lymphoma, effects of C1 inhibitor deficiency on coagulation, and the evolution of therapy-related myeloid neoplasms May 11, 2023

In this week’s episode we’ll report on the findings from a 5-year follow-up study of axicabtagene ciloleucel in refractory large B-cell lymphoma, discuss the role of C1 inhibitor deficiency in coagulation and venous thrombosis, and learn how chemotherapy signatures can be used to track the evolution of therapy-related myeloid neoplasms.

Gut microbiota and outcomes in DLBCL, NFIA-ETO2 fusion cooperates with TP53 in leukemogenesis, and the impact of nirmatrelvir + ritonavir on CLL patient outcomes during the Omicron surge May 04, 2023

In this week’s episode we'll review imbalances in gut microbiota may impact the efficacy and safety of immunochemotherapy in patients with diffuse large B-cell lymphoma. Next, the NFIA-ETO2 fusion, found exclusively in pediatric patients with pure erythroid leukemia, impairs the normal process of erythroid differentiation. Finally, we'll look at the effectiveness of nirmatrelvir plus ritonavir in patients with CLL infected with SARS-CoV-2 during the Omicron surge.

Revised response criteria for high-risk MDS, machine learning guides diagnosis of bone marrow failure syndromes, and RhD-positive transfusions for Asian-type DEL patients with serologic RhD-negative typing Apr 27, 2023

In this week’s episode, we’ll discuss the newly revised International Working Group response criteria for patients with higher-risk MDS, learn more about the utility of machine learning in the differential diagnosis of bone marrow failure, and discuss whether patients with the Asian-type DEL allele, who type as serologic Rh-D-negative, can be safely transfused with RhD-positive blood.

AIHA during pregnancy, rapid immune tolerance induction in severe hemophilia A, and aging changes control of HSC proliferation Apr 20, 2023

In this week’s episode we will review treatment and outcomes for patients with autoimmune hemolytic anemia during pregnancy. Next, rapid immune tolerance induction in patients with hemophilia A and high-titer inhibitors. Finally, researchers compare kinetics and cell cycle progression in hematopoietic stem cells from cord blood, young adults, and aged healthy donors.

Review Series on Classical Myeloproliferative Neoplasms Apr 20, 2023

In this episode Associate Editor, Dr. Mario Cazzola discusses the review series on Classical Myeloproliferative Neoplasms, with authors, Dr. Ann Mullaly and Dr. Alison Moliterno.

Review Series on Classical Myeloproliferative Neoplasms

Factor H variants in paroxysmal nocturnal hemoglobinuria, the role of factor XII in SCD-related thrombosis, and clinical features of therapy-related NPM1-mutated AML Apr 14, 2023

In this week’s episode, we’ll learn how rare germline genetic variants in complement factor H (CFH) affect the course of paroxysmal nocturnal hemoglobinuria, discuss the role of coagulation factor XII in thrombotic complications and vaso-occlusion associated with sickle cell disease, and learn more about the overlapping features of therapy-related and de novo NPM1-mutated AML.

Lenalidomide and genetic profiling in myeloma, T-cell immunotherapy upregulates AML cell MHC-class II, and young fecal microbiota rejuvenate HSCs Apr 06, 2023

In this week’s episode we will review optimizing the value of post-transplant lenalidomide maintenance in multiple myeloma. Next, T-cell immunotherapies targeting AML antigens upregulate MHC Class II expression on AML cells. Finally, young bugs rejuvenate old blood: transplanting fecal microbiota from younger mice into older mice improved hematopoietic stem cell function and restored lymphoid differentiation potential.

HLA-E-restricted immune response in EBV infection, the role of NRX-0492 in CLL, and NSAIDs for bone marrow failure in Ghosal Hematodiaphyseal Dysplasia Mar 30, 2023

In this week’s episode we’ll learn how HLA-E-restricted immune responses help control Epstein-Barr virus infection, discuss the activity of NRX-0492 in chronic lymphoblastic leukemia, and learn more about the efficacy of non-steroid inflammatory drugs in the treatment of bone marrow failure associated with Ghosal Hematodiaphyseal Dysplasia.

Review Series on Germ Line Predisposition to Hematologic Malignancy Mar 30, 2023

In this bonus episode Associate Editor, Dr. Mario Cazzola discusses the review series on Germline predisposition to hematologic malignancies with authors, Dr. Lucy Godley, Dr. Anna Brown, and Dr. Dennis Hickstein.

Review Series on Germ Line Predisposition to Hematologic Malignancy

Anti-malaria benefit of hydroxyurea in SCA, IL-22 in the treatment in lower GI acute GVHD, and FLT3-ITD changes depend on context in AML Mar 23, 2023

In this week’s episode we will review a study in sub-Saharan Africa where treatment of sickle cell anemia with hydroxyurea is associated with a lower incidence of malaria. New research suggests mild myelosuppression associated with hydroxyurea treatment may actually have a salutary effect. Next, a potential new treatment approach in lower GI acute GVHD. Adding an interleukin-22 therapy to corticosteroid treatment was well tolerated with a high rate of response in this very challenging patient population. Finally, common AML driver mutations such as FLT3ITD (or internal tandem duplications) orchestrate distinct transcriptional and epigenetic programs based on different genetic contexts. In the context of a common pediatric AML mutation, FLT3ITD selectively activated type I interferon signaling, suggesting a distinct therapeutic vulnerability.

Single-cell genotyping of MDS/CMML clonal output, VTE risk in diffuse glioma, and Del(1p32) is an adverse prognostic factor in myeloma Mar 16, 2023

In this week’s episode we’ll discuss how azacytidine therapy influences the contributions of mutated HSC clones to hematopoiesis in MDS and CMML, learn more about the risk of venous thromboembolism in patients with adult-type diffuse glioma, and discuss the importance of 1p32 deletions as an independent and adverse prognostic factor in myeloma.

RUNX1 isoform imbalance drives ML-DS, VWF-binding RNA aptamer for hemophilia A treatment, and EZH1/2 inhibitor valemetostat in relapsed/refractory ATL Mar 09, 2023

In this week’s episode we will review an imbalance among RUNX1 isoforms is key to the pathogenesis of trisomy 21-associated myeloid leukemia, raising the possibility that equilibrium could be restored genetically or pharmacologically. Next, an RNA aptamer demonstrating promising results in patients with hemophilia A. Lastly, phase 2 data on valemetostat, a selective inhibitor of EZH1 and 2, in relapsed or refractory adult T-cell leukemia/lymphoma.

Phase 3 trial of leniolisib in activated PI3Kδ syndrome, dabrafenib plus trametinib in relapsed/refractory hairy cell leukemia, and TγδLGL leukemia as a more symptomatic subset of leukemia Mar 02, 2023

In this week’s episode, we’ll discuss the findings from a phase 3 trial of PI3Kδ inhibitor leniolisib in activated PI3Kd syndrome, learn more about the efficacy and safety of dabrafenib plus trametinib in relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia, and review the findings from a study conducted in an international cohort of patients with Tγδ LGL leukemia.

Review Series on Banked Allogeneic Immune Effector Cells Feb 23, 2023

In this bonus episode Associate Editor, Dr. Helen Heslop discusses Banked Allogeneic Immune Effector Cells with Blood author Dr. Jeffrey Miller.

Review Series on Banked Allogeneic Immune Effector Cells

Hydroxyurea for secondary stroke prevention in SCD, mutant CALR as a rogue cytokine in MPNs, and parsing pathobiology in Burkitt lymphoma Feb 23, 2023

In this week’s episode we will first review a new clinical trial evidence that for patients with sickle cell anemia in resource limited settings, both low and moderate dose hydroxyurea are effective for secondary stroke prevention. Next, a research article showing how secreted mutant calreticulin functions as a “rogue cytokine” in myeloproliferative neoplasms, acting in a paracrine manner to promote growth of nearby tumor cells. Finally, we’ll review new research on the pathobiology of adult and pediatric Burkitt lymphoma. With the help of whole-genome sequencing, investigators unraveled distinct subgroups, which may provide a new framework for epidemiology, diagnosis, and treatment of these lymphomas.

HSCT for hypomorphic RAG deficiency, EBV-driven lymphoid neoplasms in pediatric ALL, and clonal hematopoiesis and recurrent vascular events in stroke patients Feb 16, 2023

In this week’s episode we’ll discuss the benefits of early diagnosis and hematopoietic stem cell transplant in patients with hypomorphic RAG deficiency, learn more about EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy, and analyze the associations between clonal hematopoiesis and recurrent vascular events and death in patients with ischemic stroke.

MRD dynamics during ixazomib maintenance in MM, disparities in CAR T-cell therapy for ALL, and BAX variants and resistance to BH3-mimetics in AML Feb 09, 2023

In this week's episode, we’ll discuss the dynamics of measurable residual disease, or MRD, over time in myeloma patients undergoing ixazomib maintenance. Serial measurements were feasible and provided more detailed risk stratification than single timepoint measurements—findings that could have implications for the use of MRD to guide treatment duration. Up next, a research article exploring the relationships between poverty, and lack of neighborhood opportunity, with outcomes of CAR T -cell therapy in children with acute lymphoblastic leukemia. The findings suggest opportunities for interventions to improve access for less socioeconomically advantaged children. Finally, we’ll review a report demonstrating that acquired mutations in the pro-apoptotic effector protein BAX are common in patients with AML treated with venetoclax. These and other research observations reveal BAX variants as a hurdle to the long-term success of BCL2-targeted therapy in this disease.

Itacitinib monotherapy for GVHD, the role of ERG in EVI1-driven AML, and germline DDX41 mutations in myeloid neoplasms Feb 02, 2023

In this week's episode, we’ll discuss the safety and efficacy of itacitinib monotherapy in low-risk acute GVHD, learn how ERG was discovered to be a key transcriptional target in EVI1-driven AML, and define a unique subtype of myeloid neoplasms characterized by germline DDX41 mutations.

Stem cell transplant for SCD normalizes brain blood flow, novel GALE variants disrupt platelet development, and revisiting risk classification in NPM1-mutant AML Jan 26, 2023

In this week’s episode, new research shows that in children with sickle cell disease, stem cell transplantation normalizes blood flow in the brain. The improvements in cerebral hemodynamics seen in this study may help explain the stroke protection seen following transplant in this high-risk patient population. Next up, a research article providing new insights on thrombocytopenia related to the GALE gene, including the identification of several previously unreported variants. The findings highlight the importance of GALE in the glycosylation of proteins that play a role in the production and function of platelets. Finally, we’ll review a brief report on NPM1-mutated AML with adverse cytogenetics in light of the updated ELN 2022 classification. In short, adverse-risk cytogenetics remain significantly associated with unfavorable prognosis under the refined definitions, supporting the recent categorization of this entity as adverse-risk.

Review Series on Single-Cell Genomics Jan 26, 2023

In this bonus episode Associate Editor, Dr. Bertie Göttgens and Dr. Ravi Majeti discuss the series on Single Cell Genomics and Heme Malignancies-Leukemia/MPNs.

Blood Review Series on Single-Cell Genomics

Allogeneic transplantation in older and infirm AML patients, cilta-cel in progressive multiple myeloma, and anti-CD20 therapy in relapsed TTP Jan 19, 2023

In this week’s episode we’ll discuss the benefits of allogeneic hematopoietic stem cell transplantation in older and medically infirm patients with AML, learn more about the efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents, and review the role of anti-CD20 therapy in relapsed immune-mediated thrombotic thrombocytopenic purpura.

Piezo antigens define a new blood group system, enasidenib in mutant-IDH2 relapsed/refractory AML, and breakthrough COVID-19 despite prophylaxis in B-cell malignancies Jan 12, 2023

In this week’s episode, we’ll discuss new research revealing that the mechanosensory ion channel Piezo1 is the elusive carrier molecule of the Er blood group antigens, thus establishing a new blood group system. Next, we review results of a randomized phase 3 trial of enasidenib versus conventional treatment in late-stage mutant-IDH2 relapsed or refractory AML. Although the primary endpoint of overall survival was not met, investigators say the risk benefit ratio remains positive. Finally, we’ll review a study showing a clinically significant risk of breakthrough COVID-19 infections in patients with B-cell malignancies despite vaccination and pre-exposure prophylaxis with tixagevimab-cilgavimab during the Omicron era. However, hospitalization rates in the study were low and no deaths were reported.

Immune thrombocytopenia in pregnancy, ASCT in adults with inborn errors of immunity, and long-term health outcomes of childhood AML survivors Jan 05, 2023

In this week’s episode we’ll discuss whether pregnancy increases the risk of bleeding in women with immune thrombocytopenia, compare the outcomes of allogeneic stem cell transplantation versus conservative management in adults with inborn errors of immunity, and learn more about the long-term health outcomes and late mortality in childhood AML survivors.

How I Treat Series: Management of High-risk Patients Following Allogeneic Transplant Jan 05, 2023

In this episode, Associate Editor, Dr. Robert Zeiser and Dr. Yi-Bin Chen discuss the series on How I Manage High-Risk Patients Following Allogeneic Hematopoietic Cell Transplantation.

IL-13/IL-4 signaling and fibrotic progression in myelofibrosis, VWF-targeted thrombolysis in acute ischemic stroke, and NK cell dysfunction in relapsed AML Dec 29, 2022

In this week’s episode, we'll discuss involvement of IL-13 and IL-4 signaling in fibrotic progression of myelofibrosis; next, we review results on a novel agent using vWF-dependent mechanisms to lyse pathological thrombi in acute ischemic stroke. Finally, we’ll shed new light on findings that implicate the GARP-TGF-beta-1 pathway in the loss of natural killer cell cytotoxicity in relapsed AML.

Effects of iron repletion on donor RBC quality, long-term outcomes in relapsed/refractory hairy cell leukemia after vemurafenib, and off-the-shelf cryopreserved platelets for detecting HIT Dec 22, 2022

In this week’s episode, we’ll discuss the effects of iron repletion on the quality of donated red blood cells and donor well-being, learn more about the long-term outcomes of patients with relapsed/refractory hairy cell leukemia after vemurafenib monotherapy, and discuss the use of off-the-shelf cryopreserved platelets for detecting heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia.

Germline predisposition variants occur in all age groups in MDS, αβ-haplo-HCT excels in children with acute leukemias/MDS, and poor outcomes after CAR T cell failure in B-cell lymphomas Dec 15, 2022

In this week’s episode, research shows that in patients with myelodysplastic syndromes, or MDS, the frequency of pathogenic or likely pathogenic germline variants is relatively high across all age groups, not just younger patients. Based on these results, it may be time to expand genetic testing to all patients. Next, we'll review primary results of a prospective, multicenter study of children with acute leukemias or MDS who underwent T-cell receptor αβ+ and CD19+ cell-depleted haploidentical HCT with reduced-toxicity conditioning. Finally, an emerging unmet need related to CAR T cell therapy: patients who progress after receiving CAR T cells have poor outcomes and no agreed upon standard of care. We’ll review findings from a large registry study demonstrating infrequent responses to post-CAR T cell treatment and short survival times, highlighting a need for novel strategies.

Predicting VTE in multiple myeloma, azithromycin promotes relapse after HSCT, and dual antigen targeted NK cells in B cell malignancies Dec 08, 2022

In this week’s episode we’ll discuss the newly developed PRISM score for risk prediction of venous thromboembolism in multiple myeloma, learn more about relapse-promoting effects of azithromycin after allogeneic stem cell transplantation, and discuss the efficacy of off-the-shelf natural killer cells in preventing antigen escape in lymphoma and leukemia.

Using MRD to guide CLL treatment intensity, donor NK cells boost immune reconstitution after haplo-BMT, and EZH2 drives retinoic acid resistance in variant APL Dec 01, 2022

In this week’s episode we discuss encouraging results of a phase 2 study using a sequential ibrutinib-venetoclax treatment approach driven by MRD findings in individual patients with chronic lymphocytic leukemia, or CLL. Next, we examine new research demonstrating that donor natural killer cells trigger release of beta-2 microglobulin by host dendritic cells, greatly accelerating donor-derived immune reconstitution after allogeneic bone marrow transplant in mice. We’ll look at the therapeutic implications of this as well. Lastly, we review a study of retinoic acid resistance in a mouse model of variant acute promyelocytic leukemia. Resistance was driven by the epigenetic regulator EZH2, which suggests the potential for an EZH2-targeted therapeutic approach.

Tolerability of CD19 CAR T cells in lymphoma, causes of platelet spherocytosis, and using prebiotics to reduce GVHD Nov 24, 2022

In this week’s episode, we’ll discuss patient-reported outcomes in the phase 3 ZUMA-7 trial of CAR T-cell therapy in second-line relapsed/refractory large B-cell lymphoma, learn more about the association between the loss of α4A- and β1-tubulin and severe platelet spherocytosis, and discuss the interaction between prebiotic galactooligosaccharides and mouse gut microbiota in graft-versus-host disease.

Transplant in adult Ph+ ALL, acalabrutinib and ventricular arrythmias, and antibody prevention of fetal/neonatal alloimmune thrombocytopenia Nov 17, 2022

In this week’s episode we discuss the role of allogeneic transplant in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. In a retrospective study, transplant provided no survival benefit in patients with rapid and deep responses to induction therapy that included BCR-ABL1 inhibitors. Up next, we discuss the evidence for an increased risk of ventricular arrythmias with use of acalabrutinib, which has emerged as a class effect of Bruton tyrosine kinase inhibitors. Lastly, we examine a novel, alloantigen-specific model to test the efficacy of a prophylactic treatment strategy for preventing fetal/neonatal alloimmune thrombocytopenia.

Restricting dietary methionine in AML, transferrin in high altitude-induced hypercoagulability, and LIF as protection against GVHD Nov 10, 2022

In this week’s episode, we’ll learn more about the impact of dietary methionine restriction on the progression of AML, discuss transferrin upregulation as a cause of high-altitude-induced hypercoagulability, and learn more about the protective effects of leukemia inhibitory factor against graft-versus-host disease.

Sickle hemoglobin activates monocytes via TLR4, germinal center B cells provide a niche for T-cell lymphoma, and a combination immunosuppression regimen for acquired hemophilia A Nov 03, 2022

In this week’s episode, we will review a study that cell-free hemoglobin S was found to induce high levels of pro-inflammatory cytokine production in monocytes. The effect is mediated by Toll-like receptor 4, or TLR4, suggesting intriguing therapeutic possibilities for sickle cell disease. Secondly, germinal center B cells with aberrant expression profiles undergo independent clonal evolution in the microenvironment of angioimmunoblastic T-cell lymphoma. New findings published in Blood elucidate mechanisms of disease pathogenesis and uncover a new potential target for treatment. Finally, an upfront combination of three immunosuppressive agents was highly effective and well tolerated in patients with acquired hemophilia A. Although prospective studies are needed, the triple regimen could be an attractive treatment option, particularly for elderly and frail patients.

Lineage switching in MLL/AF4 leukemia, ibrutinib in mantle cell lymphoma with CNS relapse, and gilteritinib plus azacitidine in newly diagnosed FLT3-mutated AML Oct 27, 2022

In this week’s episode we’ll discuss the role of epigenetic regulator genes in lineage switching in MLL/AF4 leukemia, learn more about the efficacy of ibrutinib in mantle cell lymphoma with central nervous system relapse, and discuss the findings from a phase 3 trial of gilteritinib plus azacitidine in patients with newly diagnosed FLT3-mutated AML.

Lenalidomide and subsequent TP53-mutated myeloid neoplasms, abnormal uterine bleeding after VTE, and novel tri-specific antibody for B-ALL Oct 20, 2022

In this week’s episode we will review data showing that lenalidomide promotes development of TP53-mutated, therapy-related myeloid neoplasms. Next, we'll discuss the first prospective study to evaluate abnormal uterine bleeding in women starting anticoagulation for venous thromboembolism. Lastly, we'll review an optimized tri-specific antibody that overcomes immune escape and enhances therapeutic efficacy in a patient-derived xenograft model of B-cell ALL.

Review Series on Megakaryopoiesis and Platelet Production Oct 20, 2022

Megakaryocytes contribute to multiple processes in the body, including platelet production and regulation of hematopoietic stem cells. Therefore, it is not surprising that alterations in this lineage not only affect platelets but also impact hematopoiesis in other ways. Fortunately, our understanding of megakaryocyte biology has increased significantly with the advent of advanced technologies such as next-generation sequencing and sophisticated microscopy.

Blood Review Series on Megakaryopoiesis and Platelet Production

Prognostic impact of NPM1 and FLT3 mutations in AML, progression of monoclonal B cell lymphocytosis, and creating RBCs with rare blood types in the laboratory Oct 13, 2022

In this week’s episode we’ll learn more about the prognostic impact of NPM1 and FLT3 mutations in AML, discuss the progression and survival of monoclonal B-cell lymphocytosis, and learn more about the use of red blood cells derived from pluripotent stem cells in transfusion medicine.

Transplant outcomes in adults with immunodeficiencies and erythroblastic islands as niches for terminal erythropoiesis and granulopoiesis Oct 07, 2022

In this week’s episode we'll review results of the largest retrospective study to date of allogeneic transplantation in adult patients with inborn errors of immunity. We’ll then discuss intriguing new research demonstrating that erythroblastic islands in the bone marrow foster granulopoiesis alongside terminal erythropoiesis—which lays a foundation for better understanding how blood cell production is regulated within these niches.

Ticagrelor in pediatric sickle cell disease, UBA1 translation impacts severity of VEXAS syndrome, and T-cell immunity and chemotherapy response in ALL Sep 29, 2022

In this week’s episode we’ll learn more about the negative findings from the phase three trial of ticagrelor for preventing vaso-occlusive crises in children with sickle cell disease, discuss how residual cytoplasmic UBA1 contributes to the pathogenesis of VEXAS syndrome, and learn more about the impact of host T-cell immunity in the response to chemotherapy in pediatric ALL.

Race affects treatment outcomes in iTTP, 2022 ELN AML recommendations, and a comprehensive MRD assessment in MCL Sep 22, 2022

In this week’s episode we’ll take a quick look at the latest European Leukemia Net recommendations for the diagnosis and management of acute myeloid leukemia. We’ll also describe a comprehensive analysis of a phase 3 trial indicating that MRD is a strong outcome predictor over the entire natural history of mantle cell lymphoma, setting the stage for potential risk stratification tools that may be suitable for MRD-guided treatment. We'll also look at a large US registry study demonstrating that black patients with idiopathic thrombotic thrombocytopenic purpura had a shorter time to relapse and less response to rituximab compared to white patients. These findings suggest a potential need for closer monitoring, early retreatment, and alternative treatments.

The International Consensus Classification: An interview with Drs. Daniel Arber and Elias Campo Sep 15, 2022

In this bonus episode, we’re delighted to have Dr. Dan Arber from the University of Chicago and Dr. Elias Campo from the University of Barcelona. With members of the Clinical Advisory Committee, Drs. Arber and Campo led efforts to develop the new International Consensus Classification for what we refer to as the ICC.

Tranexamic acid prophylaxis in heme malignancies, N-glycosylation as a therapeutic vulnerability in CALR-mutant MPN, and myocardial fibrosis in sickle cell anemia Sep 15, 2022

In this week’s episode we’ll discuss the efficacy of tranexamic acid prophylaxis in patients with hematological malignancies, learn more about N-glycosylation as a therapeutic vulnerability in CALR-mutant MPN, and discuss how early initiation of disease-modifying therapy may be able to reduce myocardial fibrosis in sickle cell anemia.

Rest alleviates T-cell exhaustion by bispecific antibodies, exercise vs desmopressin in mild hemophilia A, and targeting MDM2 to enhance antileukemia immunity after transplant Sep 08, 2022

Sutimlimab vs placebo in cold agglutinin disease, the impact of etoposide versus auto-transplant in PTCL, and the role of pulmonary NETs in sickle cell disease Sep 01, 2022

In this week’s episode, we review results of a randomized, placebo-controlled phase 3 trial demonstrating that targeted inhibition of C1s with the monoclonal antibody sutimlimab is effective and well tolerated in non-transfusion-dependent patients with cold agglutinin disease. We’ll also review a population-based study evaluating the impact of adding either etoposide or autologous stem cell transplantation to CHOP in young and fit patients with peripheral T cell lymphomas. Finally, we’ll review a paper that elucidates a mechanism of lung injury in sickle cell disease. It involves gasdermin-D-dependent production of neutrophil extracellular traps in the liver, which travel intravascularly to the lung, where they promote occlusion of the pulmonary microcirculation.

Rivaroxaban after cancer surgery, genetics and survival in severe aplastic anemia, and a 5-year follow up of rituximab-venetoclax in relapsed/refractory CLL Aug 25, 2022

In this week’s episode discuss the efficacy of rivaroxaban as antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer, learn more about the association between genomic variants and survival outcomes after hematopoietic cell transplantation in severe aplastic anemia, and discuss the long-term safety and efficacy of fixed-duration venetoclax plus rituximab in relapsed/refractory CLL.

Stroke in hereditary TTP, and germline DDX41 variants as risk factors and prognostic markers in myeloid neoplasms Aug 18, 2022

In this week’s episode, we’ll learn more about neuropsychiatric manifestations and stroke risk in hereditary TTP, discuss germline DDX41 variants as predisposing factors to myeloid neoplasms, and learn more about the prognostic impact of DDX41 mutations in adults with intensively treated AML.

Cost effectiveness of first-line daratumumab in MM, base-edited CAR T cells for T-ALL, and the role of SETBP1 mutations in chronic neutrophilic leukemia Aug 11, 2022

In this week’s episode new research suggesting that, in patients with transplant-eligible multiple myeloma, adding daratumumab to first-line combination regimens may be a more cost effective strategy than saving it for second-line use. We’ll also review the work of researchers who applied base-editing technology to develop a complex and potent CAR T cell product for potential “off-the-shelf” use in patients with T-cell leukemias and other CD7-positive malignancies. Finally, we’ll review a paper that elucidates the role of SETBP1 mutations in chronic neutrophilic leukemia, pointing the way toward a potential multi-pronged therapeutic approach to this rare myeloproliferative neoplasm.

Immune thrombocytopenia and adenoviral SARS-COV2 vaccines, genomics, and a risk assessment model of anti-CD19 CAR T-cell treatment outcomes in lymphoma Aug 04, 2022

In this week’s episode we’ll discuss the factors influencing the development of immune thrombocytopenia after administration of the ChAdOx1 nCov-19 vaccine, learn about the genomic features underlying anti-CD19 CAR T-cell treatment failure in lymphoma, and introduce a new predictive model for risk assessment before CAR T-cell therapy for large B-cell lymphoma.

Naturally selected CD7 CAR T cell therapy for T-lineage malignancies, CD4+ T cell exhaustion and PD-L1 inhibition in B-ALL, and tPA-induced phosphorylation of occludin in stroke Jul 28, 2022

In this week’s episode we review a novel approach to generating autologous CD7-specific CAR T therapy for patients with T-cell malignancies that overcomes a key limitation: target-driven fratricide. We’ll also learn about new research pinpointing a key subset of exhausted CD4+ T cells in B- ALL, which also provides a rationale for combining tyrosine kinase inhibitors and PD-L1 blockers to reverse exhaustion and enhance leukemia clearance. Finally, we’ll discuss studies in a mouse model of acute ischemic stroke, showing that inhibiting phosphorylation of a tight junction protein in endothelial cells reduces risk of intracranial hemorrhage after treatment with recombinant tissue plasminogen activator.

Role of PIEZO1 in leukocyte extravasation, CD8+ T-cell activation in macrophage activation syndrome, and ABO O blood group as a novel risk factor for HIT Jul 21, 2022

In this week’s episode we first review new work revealing the critical role of the tension-sensitive cation channel PIEZO1 in the transendothelial migration of leukocytes. We’ll also review new research suggesting that CD8+ T-cells dimly expressing the CD4 antigen are increased in patients with various forms of secondary HLH, a finding that may have diagnostic, prognostic, and therapeutic significance. Finally, we’ll review a large, genome-wide association study identifying the ABO O blood group as a novel risk factor for heparin-induced thrombocytopenia—a finding that could have implications for prediction of this syndrome and for the management of related conditions.

Long-term ibrutinib-rituximab vs FCR in CLL, procoagulant platelet sentinels in prevention of inflammatory bleeding, and new SERPINC1 variants in thrombophilia Jul 14, 2022

In this week’s episode we’ll compare the long-term outcomes of ibrutinib-rituximab combination therapy versus FCR chemoimmunotherapy in chronic lymphocytic leukemia, discuss the role of procoagulant platelet sentinels in inflammatory bleeding, and learn more about variants in the SERPINC1 gene encoding antithrombin that cause severe thrombophilia.

Malignancy risk from genetically modified immune effector cells, p53 immunohistochemistry as a new tool in AML, and phenotypic escape from CD19-directed immunotherapies. Jul 07, 2022

Today we’ll learn more about the risk of subsequent malignancies in patients treated with genetically modified immune effector cells, discuss how p53 immunohistochemistry can be a global readout for TP53 alterations in AML, and uncover the role of CD19-negative CD22-positive B-cell progenitors in immune escape from CD19-directed therapies.

Overcoming CAR T cell resistance in myeloma, why anti-CCR4 antibody therapy in CTCL sometimes fails, and corticosteroids increase risk of VOE in sickle disease Jun 30, 2022

In this week’s episode we review a novel strategy for overcoming resistance to CAR T cell therapy that involves the dual targeting of myeloma cells and cancer-associated fibroblasts. We’ll also explore a recent report demonstrating that loss of CCR4 expression is common after treatment of CTCL with the anti-CCR4 antibody mogamulizumab. Finally, we’ll review real-world data demonstrating an association between corticosteroid exposure and risk of vaso-occlusive episodes in patients with sickle cell disease, providing further evidence that steroids should be avoided in this setting.

Salvage therapy with NICE for Hodgkin lymphoma, BMP2/SMAD pathway activation in leukemic transformation, and the role of zinc in T-cell reconstitution after HSCT Jun 23, 2022

In this week’s episode we’ll learn more about salvage therapy with nivolumab plus or minus ICE (or NICE) for Hodgkin lymphoma, discuss the role of BMP2/SMAD pathway activation in leukemic transformation, and learn more about the role of zinc in T-cell reconstitution after transplantation.

MRD and post-transplant outcomes in older AML patients, enhancer hijacking in a novel high-risk B-other ALL subtype, and ruxolitinib in pediatric HLH Jun 16, 2022

In this week’s episode we will discuss new data demonstrating that, in older patients with AML, post-transplant relapse risk is driven by clinical and molecular features present at diagnosis, but not remission MRD. We’ll also explore two studies that characterize a novel high-risk B-ALL subtype, defined by two unique genomic alterations that includes a deletion resulting in enhancer hijacking that deregulates expression of the CDX2 homeobox transcription factor. Finally, we’ll review results of a large, single-arm phase 2 trial providing encouraging clinical evidence for the use of ruxolitinib as a front-line treatment for pediatric hemophagocytic lymphohistiocytosis.

Anti-PF4 antibodies after Covid vaccination, CAR T-cell therapy for CNS leukemia, and advances in Diamond-Blackfan anemia Jun 09, 2022

In this week's episode, we’ll learn more about the interaction between anti-PF4 antibodies and anticoagulants in vaccine-induced thrombotic thrombocytopenia, discuss the efficacy and safety of CD19-specific CAR T-cell-based therapy in B-cell ALL patients with central nervous system leukemia, and learn more about erythroid cell-extrinsic factors that can inhibit erythropoiesis in adjacent cells.

Fixed-duration ibrutinib + venetoclax for CLL, aryl hydrocarbon receptor in idiopathic pneumonia syndrome, and VWF propeptide and multimerization Jun 02, 2022

In this week's episode, we discuss results from the international phase 2 CAPTIVATE study showing that in patients with treatment-naive CLL, fixed-dose ibrutinib plus venetoclax yields deep and durable responses and promising progression-free survival. We’ll also explore data that show that aryl hydrocarbon receptor is a critical inflammation checkpoint in the lung epithelium—a finding that may have therapeutic implications for idiopathic pneumonia syndrome. Lastly, we’ll review new insights into the role of von Willebrand Factor propeptide in facilitating multimer formation, shedding light on a potential novel treatment approach for type 2a von Willebrand disease.

HEATR3 variants as a new cause of Diamond-Blackfan anemia, zanubrutinib in mantle cell lymphoma, and HMGB1 inhibits Epo signaling in anemia of inflammation May 26, 2022

In this week's episode we discuss the role of HEATR3 variants as a new cause of Diamond-Blackfan anemia, learn more about the long-term efficacy and safety of zanubrutinib in relapsed or refractory mantle cell lymphoma, and uncover an unexpected role for HMGB1 in anemia of inflammation by inhibiting erythropoietin signaling.

HLA-DQ heterodimers and transplantation, the genomic landscape of LGL leukemia, and an updated classification of hemochromatosis May 19, 2022

In this week’s episode we’ll feature new research demonstrating that certain HLA-DQ heterodimers can help predict clinical outcome following hematopoietic cell transplantation. Next, we’ll review a recent integrated and comprehensive genomic analysis that sheds new light on the molecular characteristics of large granular lymphocyte leukemia and its subtypes. Finally, we’ll review the work of a group that proposes a new and more accessible hemochromatosis classification system based on clinical characteristics and genetic features.

Role of macrophage NOX2 in alveolar homeostasis, hydroxyurea versus peginterferon alfa-2a in high-risk PV and ET, and the emerging PV treatment landscape May 12, 2022

In this week’s episode we’ll discuss an undescribed role for NOX2 in maintaining lung homeostasis through suppression of alveolar macrophage activation. We’ll also cover results of a phase 3 randomized trial that compares the safety and efficacy of hydroxyurea and peginterferon alfa-2a in patients with high-risk polycythemia vera and essential thrombocythemia (or PV and ET, respectively). Finally, we’ll go more in depth on the emerging treatment landscape for PV, and the limits of current clinical trial endpoints.

Microbiome and CD4 T-cell recovery after allogeneic HCT, and a paradigm shift to CAR T-cells in the second line for large B-cell lymphoma? May 05, 2022

In this week’s episode we’ll discuss the effects of intestinal microbial diversity on patient outcomes following allogeneic hematopoietic cell transplant and review the results of three different phase 3 trials comparing CAR T-cells to autologous stem cell transplant in patients with refractory or early relapsing large B cell lymphoma, which have the potential to result in a paradigm shift in the standard of care for second-line therapy.

Canakinumab in SCA, antigen-specific donor T-cells to prevent post-transplant relapse in ALL, and nasopharyngeal mucosal immunity defects in transplanted SCID patients Apr 28, 2022

In this week’s episode, we’ll discuss the efficacy of canakinumab in children and young adults with sickle cell anemia, learn more about the use of donor-derived multiple leukemia antigen specific T-cell therapy to prevent relapse in post-transplant patients with ALL, and discuss the defects in nasopharyngeal mucosal immunity in patients with severe combined immunodeficiency after hematopoietic stem cell transplantation.

Timing (and utility) of CNS prophylaxis in DLBCL, Apollo deficiency in a bone marrow failure syndrome, and GATA1 mutants in congenital anemia Apr 21, 2022

In this week’s episode we’ll cover a retrospective study on the timing of high-dose methotrexate CNS prophylaxis in diffuse large B-cell lymphoma, results of which suggest end-of-treatment delivery might be preferred to earlier administration. The second research article describes how biallelic Apollo variants lead to an inherited bone marrow failure syndrome that resembles dyskeratosis congenita, albeit with normal telomere length. We’ll conclude with research revealing how a rare form of congenital anemia is caused by novel missense mutations in GATA1.

Obinutuzumab plus lenalidomide in advanced follicular lymphoma, mechanisms of anemia in children with malaria, and granulocyte microvesicles for septic shock Apr 14, 2022

In this week’s episode we’ll discuss the efficacy of the obinutuzumab-lenalinomide combination in advanced follicular lymphoma, learn more about the underlying mechanisms of anemia in children infected with Plasmodium falciparum, and discuss how granulocyte microvesicles could improve outcomes in septic shock.

Structural racism and AML survival, promoter competition and hemoglobin switching, and CAR T-cell therapy and high-risk cytogenetics in ALL Apr 07, 2022

In this week’s episode we’ll first cover a research article demonstrating the striking contribution of neighborhood disadvantage to racial and ethnic disparities in survival in patients with acute myeloid leukemia. The second research article provides a model for understanding how disruption of the adult-globin promoter may alleviate promoter competition, thereby reactivating fetal gamma-globin gene expression. We will close with a research article showing that CD19-directed CAR T-cell therapy provides durable remissions in patients with relapsed or refractory ALL across cytogenetic categories, including those patients with high-risk cytogenetics.

Targeting the PBX1-FOXM1 axis in myeloma, SF3B1 mutations in MDS, and pulmonary artery hypertension-associated mortality in β-thalassemia patients Mar 31, 2022

In this week's podcast, we’ll discuss the role of the PBX1-FOXM1 axis in multiple myeloma, learn more about the pathobiology of SF3B1 splicing factor mutations in myelodysplastic syndromes with ring sideroblasts, and discuss mortality rates due to pulmonary arterial hypertension in patients with β-thalassemia.

Novel high-risk subtypes in adult B-ALL, Liso-cel CAR-T therapy in CLL, and liquid biopsies in large B-cell lymphomas Mar 24, 2022

In this week's podcast, we’ll cover a research article that describes two novel subgroups of adult B-cell ALL with high expression of CDX2 and IDH mutations that are linked to poor prognosis. Next, we'll cover results from TRANSCEND CLL 004, a phase 1 study of the CAR T cell therapy, liso-cel, in patients with relapsed or refractory CLL. We will close with research that provides new insights into how analysis of circulating tumor DNA could inform management of patients with aggressive B-cell lymphomas.

Effective treatments for kaposiform hemangioendothelioma, causes of vascular dysfunction in sickle cell patients, and better strategies to select therapy in older adults with AML Mar 17, 2022

In this week's podcast, discuss the efficacy of siroliumus plus prednisolone in kaposiform hemangioendothelioma with the Kasabach-Merritt phenomenon, learn more about the association between SOD2 V16A and vascular dysfunction in patients with sickle cell disease, and discuss the value of geriatric assessment in predicting outcomes in older adults with AML.

COVID-19 vaccination in patients with blood cancers and recalibrating the HLA barrier in haploidentical stem cell transplantation Mar 10, 2022

In this week's podcast, we’ll focus on 2 reports on clinical outcomes following COVID-19 vaccination in patients with hematologic malignancies. Despite full or partial vaccination, these patients have an increased risk of poor outcomes compared to matched controls or the general population. In a third report, we discuss new data on HLA-mismatching and outcomes of haploidentical transplants.

Cell therapy options for chemo-sensitive DLBCL, PIGA mutations in a novel subtype of hemochromatosis, and triplet combination therapy in high-risk CLL Mar 03, 2022

In this week's podcast, we’ll compare the efficacy of autologous stem cell transplant to CAR T-cell therapy for relapsed diffuse large B-cell lymphoma, learn more about a novel subtype of hemochromatosis caused by constitutional PIGA mutations, and discuss the findings from a phase 2 trial of obinutuzumab, ibrutinib and venetoclax in patients with untreated high-risk CLL.

Germline predisposition mutations in AML, a new way to resolve NETs, and venetoclax and BAX mutations in normal myeloid cells of CLL patients Feb 24, 2022

In this week's podcast, we’ll look at work from researchers who found pathogenic or likely pathogenic variants of cancer predisposition genes in nearly 14% of adults with AML. Next, we’ll review research demonstrating that a recently identified series of resolvins reduces neutrophil extracellular trap formation and enhances clearance of these NETs by macrophages, suggesting a new mechanism for the resolution of inflammation and coagulopathies associated with various infections. We’ll conclude with research demonstrating that patients with CLL undergoing long-term venetoclax treatment exhibit a high incidence of cytopenias, clonal hematopoiesis, and myeloid neoplasms, and may acquire BAX mutations in normal myeloid cells.

Ovarian reserve in sickle cell anemia, genomic landscape of adult T-cell leukemia/lymphoma, and a new prognostic index for HLH-associated heme malignancies Feb 17, 2022

In this week’s podcast, we’ll discuss diminished ovarian reserve in young women with sickle cell anemia, learn more about genomic alterations in adult T-cell leukemia/lymphoma, and review a novel diagnostic and prognostic index for malignancies associated with hemophagocytic lymphohistiocytosis.

Role of HBO1 in HSC function, robust MRD analysis in multiple myeloma, and cardiac ferroptosis in sickle cell disease Feb 10, 2022

In this week’s podcast, we’ll look at research demonstrating that the histone acetyltransferase HBO1 is an essential regulator of hematopoietic stem cell function during adult hematopoiesis. Next, we’ll review a large, combined analysis confirming the prognostic value of MRD assessed with next-generation sequencing in 4 randomized trials evaluating daratumumab-based therapies. We’ll conclude with research demonstrating that ferroptosis, a specific type of regulated cell death, is a key mechanism of cardiomyopathy in sickle cell disease.

The ARID3A transcription factor suppresses leukemia, a COVID-19 booster shot benefits CLL patients, and advances in the genetics of congenital neutropenia Feb 03, 2022

In this week’s podcast, we’ll discuss the role of megakaryocytic transcription factor ARID3A in leukemia suppression, learn more about the efficacy of a third Pfizer BNT162b2 mRNA COVID-19 vaccine dose in patients with chronic lymphocytic leukemia, and discuss the association of heterozygous caseinolytic peptidase B variants with congenital neutropenia.

Sustained MRD negativity & outcomes in myeloma, therapeutic targeting of VWF in TTP, and improving CAR T-cells in CLL with PI3 kinase inhibition Jan 28, 2022

On this week’s podcast, we’ll review a recent analysis of phase 3 daratumumab studies looking at the prognostic impact of sustained minimal residual disease, or MRD negativity in patients with multiple myeloma. Next, we’ll hear more about a novel thrombolytic agent targeting von Willebrand factor that may represent a promising approach for the treatment of thrombotic thrombocytopenic purpura. We’ll conclude with a study demonstrating that PI3 kinase inhibitor duvelisib can be used to enhance the in vivo efficacy of CAR T cells in CLL.

Does route of CNS prophylaxis for DLBCL matter?, the connection between CHIP and COPD, and ATRA plus low-dose rituximab in ITP Jan 20, 2022

In this week’s podcast, we’ll discuss real-world outcomes comparing route of CNS prophylaxis for aggressive non-Hodgkin lymphomas, learn more about the association of clonal hematopoiesis with chronic obstructive pulmonary disease, and discuss the efficacy of all-trans retinoic acid plus low-dose rituximab in corticosteroid-resistant or relapsed immune thrombocytopenia.

A spectrum of ALK-positive histiocytosis, and metabolites as biomarkers for GvHD diagnosis and risk assignment Jan 13, 2022

On today’s podcast, we’ll explore the largest case series to date describing ALK-positive histiocytosis. The authors provide new insights on the disease and its treatment with ALK inhibitors, which can provide durable responses. We’ll also review with a study that pinpoints alpha-ketoglutaric acid as consistently elevated in pediatric chronic GvHD, and finds unique metabolomic patterns that appear to distinguish different GvHD subtypes.

Long-term outcomes in severe aplastic anemia, cytoprotective effects of factor VIIa, and the role of IL-1 in hematopoietic stem cell ageing Jan 06, 2022

In this week’s podcast, we’ll talk about the long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag, learn more about anti-inflammatory and cytoprotective effects of factor VIIa, and discuss the role of IL-1 in microbiome-induced ageing of hematopoietic stem cells in mice.

CRISPR cure for XMEN disease?, JAK inhibition in T-cell lymphomas, and intracranial hemorrhage in hemophilia Dec 30, 2021

In this week’s episode, we’ll review a research article that provides the first description of a targeted gene insertion approach to correct the genetic mutation underlying XMEN disease. Next, we’ll cover results of a phase 2 study that provides proof-of-principle that the JAK/STAT pathway is a promising target for the treatment of peripheral T-cell lymphomas. We’ll close with a study providing precise and up-to-date estimates on the incidence of intracranial hemorrhage in patients with hemophilia that could have important implications for preventive strategies.

Antigen presentation by platelet extracellular vesicles, fibril-reactive monoclonal antibody therapy for AL amyloidosis, and targeting gasdermin D in sepsis Dec 23, 2021

In this week’s episode, we’ll review a research article demonstrating that some platelet-derived extracellular vesicles harbor proteasomes that can process and present antigens via MHC class I molecules. Next, we’ll review results of a phase 1 study of a fibril-reactive monoclonal antibody that was well tolerated and led to rapid, sustained organ responses in patients with AL amyloidosis. We’ll close with a research article suggesting that the pore-forming protein gasdermin D, which plays a crucial role in the release of neutrophil extracellular traps, is a promising drug target in sepsis.

Mesenchymal stromal cells in SCD, CAR T-cell-mediated hematotoxicity in B-cell lymphoma, and dual cytokine blockade in GVHD Dec 16, 2021

In this week’s episode, we’ll talk about the functional properties of mesenchymal stromal cells in sickle cell disease, learn more about CAR T-cell-mediated hematotoxicity in relapsed/refractory B-cell lymphoma, and discuss dual cytokine blockade in graft-versus-host disease.

PROTACs for JAKs in CRLF2-rearranged ALL, risk stratification in Down syndrome-associated leukemia, and how losing sialic acid activates immune cells in ITP Dec 09, 2021

In this week’s episode, we’ll learn about a new approach for targeting Janus kinases in CRLF2-rearranged ALL, discuss risk stratification for myeloid leukemia in children with Down syndrome and learn more about how sialic acid alterations on megakaryocyte antigens regulate immune cells and platelet production.

Belumosudil for chronic GVHD, mechanistic insights into VITT, and factors driving molecular response in IFNα-treated MPNs Dec 02, 2021

First on today’s podcast, we’ll review results of a randomized phase 2 study demonstrating that inhibition of ROCK2 with belumosudil is well tolerated and effective in patients with steroid-refractory graft-versus-host disease. Next, we’ll review the work of researchers who have uncovered new insights into the immunopathogenesis of vaccine-induced immune thrombotic thrombocytopenia. And we’ll close with a report of a prospective longitudinal analysis that elucidates the dynamics of mutated hematopoietic stem and progenitor cells during therapy with interferon-alpha in patients with BCR-ABL1 negative myeloproliferative neoplasms.

Post-vaccination COVID-19 in patients with hematologic malignancies Dec 01, 2021

All four studies included in this podcast present preliminary data with modest numbers of patients, and therefore, the findings should be interpreted with these limitations. Likewise, the impact of specific strains and waning antibody levels after COVID-19 vaccination will require further follow-up, since the Delta variant was not the dominant strain in circulation at the time of this research. The first two studies assess the immune responses to vaccination in two specific high-risk populations, namely, patients with lymphoma and multiple myeloma. The last two studies, one from a large European consortium and the other based on nationwide data from Israel, report on the incidence, risk factors and short-term outcomes of COVID-19 breakthrough infection in vaccinated patients with hematologic malignancies.

Asciminib versus bosutinib in CML; dopamine signaling and hematopoietic stem cells; complement factor C5 and VTE risk Nov 25, 2021

In this week’s episode, we’ll learn more about the efficacy of asciminib in patients with chronic myeloid leukemia who are resistant or intolerant to two or more tyrosine kinase inhibitors, discuss the role of dopamine signaling in hematopoietic stem and progenitor cell function, and learn more about elevated plasma concentration of complement factor C5 as a risk factor for venous thromboembolism.

Danicopan add-on therapy in PNH, neural networks to identify bone marrow cells, and RNA editome and hematopoiesis Nov 18, 2021

In this week’s episode, we’ll review results of a phase 2 study showing the beneficial effects of a first-in-class factor D inhibitor as add-on therapy in PNH patients who remain anemic and are transfusion-dependent despite C5 inhibition. Next, we’ll review the work of researchers who have developed a neural network that they say is highly accurate in differentiating between bone marrow cell morphologies. We’ll close with a report demonstrating that RNA editing of antizyme inhibitor 1, or Azin1, is a novel regulator of hematopoietic cell fate that can influence self-renewal and differentiation.

Machine learning in classification of AML, aging bone marrow in leukemia, and treating bleeding disorders of unknown cause Nov 11, 2021

In this week’s episode, we’ll learn more about the application of machine learning in molecular subclassification and prognostication of acute myeloid leukemia or AML, discuss the role of aging bone marrow in leukemia progression, and learn more about the challenges in treating bleeding disorders of unknown cause.

Anti-CD36-antibody therapy of neonatal alloimmune thrombocytopenia, costs of hemophilia B gene therapy, and insights into erythroid maturation Nov 04, 2021

In this week’s episode, we’ll review a research article showing beneficial effects of prenatal immunotherapy in a mouse model of anti-CD36-mediated fetal and neonatal alloimmune thrombocytopenia. Next, we’ll look at results of a simulation analysis suggesting that gene therapy for hemophilia B is more cost-effective than on-demand or prophylactic factor treatment. We’ll conclude with a report which provides important new insights into regulation of terminal erythroid maturation at the transcriptional level that may help improve our understanding of normal and abnormal erythropoiesis.

Genetic risks for CMV after BMT, multiplex gene editing to reactivate HbF, and rewiring plasma cells in light chain amyloidosis and myeloma Oct 28, 2021

In this week’s episode, we’ll discuss an analysis of genetic risks for CMV infection after an allogeneic hematopoietic stem cell transplant, learn more about a new multiplex gene editing approach to reactivate fetal hemoglobin in thalassemia, and discuss transcriptional rewiring of normal plasma cell development in light-chain amyloidosis and myeloma.

Omidubicel vs standard umbilical cord blood transplant, CAR T-cell associated lymphomas, and CD63 and ferritin export Oct 21, 2021

In this week’s episode, we’ll review results of a phase 3 randomized study demonstrating shorter time to neutrophil and platelet recovery with an ex vivo expanded hematopoietic progenitor cell product called omidubicel as compared to standard umbilical cord transplantation. Next, we’ll look at preliminary data on the development of lymphomas originating from piggyBac-modified CD19 CAR T-cells, sounding a note of caution for researchers exploring new gene modification methodologies for CAR T-cell production. We’ll conclude with a report suggesting that the vesicular protein CD63 may orchestrate the transfer of iron-rich ferritin among cells.

Iron homeostasis and anemia of inflammation in TB, and long-term outcomes of gene therapy in adenosine deaminase-deficient SCID patients Oct 14, 2021

In this week’s episode, we will review a study that prospectively followed tuberculosis patients after treatment initiation to evaluate iron handling during the resolution of inflammatory anemia. We will also examine clinical benefit and long-term safety of gamma-retroviral gene therapy in patients with adenosine deaminase deficient severe combined immunodeficiency.

Immune megakaryocytes, PD1 deletions in CTCL, and COVID-19 vaccine and VITT Oct 07, 2021

In this week’s episode, we’ll review a study providing new insights on megakaryocyte diversity and function, including a unique subpopulation that may act as immune cells. Next, we’ll review research that intriguingly reveals a putative role for the PD1 gene in cutaneous T-cell lymphoma. Lastly, we’ll conclude with a report demonstrating a lack of cross-reaction between the antibodies that cause vaccine-induced thrombocytopenia and thrombosis, and the COVID-19 spike protein.

Inhibition of P-selectin as an anticoagulant, prognostic implications of CEBPA mutations in AML, and treating sickle cell disease with voxelitor Sep 30, 2021

In this week’s episode, we’ll review a study that demonstrates the efficacy of a synthetic inhibitor termed P-G6 that blocks P-selectin signaling and reduces thrombus formation in a pre-clinical model of non-occlusive venous thrombosis, learn more about how biallelic and single bZip CEBPA mutations have an equally favorable prognostic impact in acute myeloid leukemia, and examine the effects of modifying the pathophysiology of sickle cell anemia with therapeutic agents that increase oxygen affinity.

Caution on JAK inhibitors in HLH, CD44 loss sensitizes AML to venetoclax, and new insights on cell cycle control in Richter transformation Sep 23, 2021

In this week’s episode, we review results of preclinical investigations that sound a note of caution regarding the potential use of JAK inhibitors as treatment for hemophagocytic lymphohistiocytosis (or HLH), research that provides new insights on how CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax, and conclude with a report that demonstrates cooperation between B cell receptor signaling and genetic lesions in CDKN2A, CDKN2B and TP53 in Richter transformation.

Improved risk assessment in adult BCR-ABL1-negative B-ALL, value of clone metrics in clonal cytopenias, a placental protease generates a peptide to inhibit NET formation Sep 16, 2021

In this week’s episode, we will review an integrated analysis of one of the largest adult BCR-ABL1-negative B-ALL patient cohorts treated in a single trial, learn more about the genotypic and phenotypic features of patients with clonal cytopenias, and look at a study showing that a serine protease expressed in the placenta cleaves α1-antitrypsin to generate a fragment that inhibits formation of neutrophil extracellular traps in neonates.

Fixed-duration venetoclax in relapsed CLL, differing effects of invariant NK T cells, and under recognition of rare TERT variants in MDS Sep 09, 2021

In this week’s episode, we’ll review updated results of a phase 1b study that provide strong support for the use of fixed-duration venetoclax in patients with relapsed or refractory CLL. Next, we’ll review a research paper that provides new insights on the different subtypes of invariant natural killer T cells, which appear to have diverse immunoregulatory properties and anti-tumor effects. We will finish up with a report indicating that rare variants in the telomerase gene, TERT, are underrecognized in patients with myelodysplastic syndromes, providing a new insight into the germline genetic component of disease pathophysiology.

Activated BCL11B in acute leukemias, SARS-CoV-2 antibody responses in lymphoma patients receiving B-cell therapies, and PD-L1 in neutrophil apoptosis and tissue inflammation Sep 02, 2021

In this week’s episode, we will review a study that shows that BCL11B is an important oncogene in acute leukemias with myeloid and T-lymphoid features, learn more about antibody responses to SARS-CoV-2 vaccination in lymphoma patients receiving B-cell directed therapies, and examine the role of programmed death ligand 1 (or PD-L1) and the PI 3 kinase-AKT survival pathway in delayed neutrophil apoptosis at sites of tissue inflammation.

Review Series on Mechanisms of Hematologic Malignancies Aug 26, 2021

To reach the goal of curing currently incurable hematologic malignancies, we need to go beyond focusing on single gene mutations and gain deeper understanding of the consequences of genetic alterations on gene-regulatory pathways. Edited by John Crispino, these 5 cutting-edge reviews from leaders in the their fields not only summarize our current understanding of key pathways that contribute to myeloid malignancies, but also discuss new therapeutic avenues related to them. They provide a springboard for further groundbreaking basic and clinical advances in hematologic malignancies.

Review Series on Mechanisms of Hematologic Malignancies

IFN-λ therapy for GvHD, mechanism of decitabine in ITP, and TET2 mutations in chronic NK-LGL leukemia Aug 26, 2021

In this week's episode, we will review a study that proposes IFN-λ therapy as a novel strategy to boost gut protection in GvHD, examine the immunomodulatory effects of decitabine in ITP, and learn about the discovery of TET2 mutations in chronic natural killer large granular lymphocyte leukemia

Choosing chemotherapy for older patients with AML, the role of the microenvironment in pediatric ALL, and efficacy of thrombopoietin receptor agonists in elderly patients with ITP Aug 19, 2021

In this week's episode, we will review a report on a clinical prognostic tool that identifies which group of older, fit acute myeloid leukemia patients may derive survival benefit from intensive induction and consolidation chemotherapy, learn more about how pediatric acute myeloid leukemia cells connect with mesenchymal stromal cells and the potential to exploit these cell-cell contacts in AML treatments, and examine the effects of eltrombopag and romiplostim in elderly patients with immune thrombocytopenia.

Brentuximab plus nivolumab in refractory/relapsed Hodgkin lymphoma, the signature of aging hematopoietic stem cells, and hepatocyte neogenin in iron homeostasis Aug 12, 2021

In this week's episode, we’ll discuss the safety and efficacy of brentuximab vedotin in combination with nivolumab in patients with relapsed and refractory classical Hodgkin lymphoma, learn more about the aging signature of murine hematopoietic stem cells, and discuss the role of hepatocyte neogenin in iron homeostasis.

Latest Research on the Intensity of AML Therapy in Older Patients, Platelets and T cell Activity in Sepsis, and Genotyping for CNS Lymphoma Aug 05, 2021

In this week's episode, we’ll start by reviewing an intriguing study that, while not randomized, calls into question whether less-intensive induction therapies provide a survival or quality of life benefit in older patients with AML. Next, we will review the somewhat surprising findings from human and mouse model studies demonstrating that platelets downregulate T cell activity during sepsis, a finding that is associated with reduced survival. We will close with a report on a targeted genotyping approach that could reduce diagnostic and treatment delays in patients with primary CNS lymphoma.

Vaccine-induced Immune Thrombotic Thrombocytopenia Jul 29, 2021

Today’s episode is a special edition that focuses exclusively on vaccine-induced immune thrombotic thrombocytopenia, or VITT, a rare but potentially fatal syndrome associated with adenovirus-based COVID-19 vaccines. The VITT syndrome is characterized by thrombocytopenia and thrombosis in association with platelet-activating anti-platelet factor 4 antibodies. First, we’ll review an insightful Spotlight article on what is known about VITT to date. Then we’ll discuss two new brief reports in Blood that provide additional insights on VITT clinical manifestations, laboratory findings, and disease management.

Latest research in post-transplant cyclophosphamide in matched unrelated versus haploidentical donors, outcomes in patients with AITL, and high molecular weight kininogen in acetaminophen-induced liver injury Jul 22, 2021

In this week’s episode, we will learn more about the use of high-dose post-transplant cyclophosphamide in matched unrelated donors versus HLA haploidentical grafts, review prognostic factors and outcomes from the largest cohort of patients with angioimmunoblastic T-cell lymphoma reported to date, and look at a study that suggests that high molecular weight kininogen contributes to acetaminophen-induced liver injury.

Latest research in thrombosis in pediatric COVID-19, prognostic tool for very early stage CLL, and frontline treatment for newly diagnosed myeloma Jul 15, 2021

In this week's episode, our studies include an analysis of thrombosis in pediatric patients with COVID-19, the predictive value of the CLL-international prognostic index in monoclonal B-cell lymphocytosis and Rai 0 stage CLL, and results from a phase 2 trial in newly diagnosed multiple myeloma patients treated with frontline carfilzomib, lenalidomide, and dexamethasone with autologous stem cell transplant.

Latest Research: Immunity to CMV, lymphoma microenvironment, and tPA induced bleeding Jul 08, 2021

In this week's episode, we will review a study that addresses the issue of reconstitution of immunity to cytomegalovirus in transplant patients receiving the antiviral drug letermovir, learn more about the role extracellular vesicles play in forming a tumor supportive stromal cell niche in follicular lymphoma, and finally, look at a report identifying a mechanism that couples the treatment of acute ischemic stroke with tissue plasminogen activator to the development of intracerebral hemorrhage.

VEXAS: A Newly Identified Adult-onset Hemato-inflammatory Syndrome Jul 01, 2021

Today’s podcast is a special edition that focuses exclusively on VEXAS syndrome, a newly identified adult-onset inflammatory syndrome with associated hematologic manifestations. VEXAS syndrome is a poor-prognosis disease caused by somatic mutations in the X-linked gene, UBA1. It was first reported by Beck and colleagues in the New England Journal of Medicine in December 2020.

Season 2, Episode 25 Jun 24, 2021

In this week’s episode, we will review a study that uses a combination of mouse models to identify IL-19 as a potent cytokine capable of promoting expansion and proliferation of neutrophils, examine the effects of targeted therapies on autoimmune cytopenia in patients with chronic lymphocytic leukemia, and learn about the mechanism of excessive complement activation caused by mutations in factor H-related protein 1 in patients with atypical hemolytic uremic syndrome.

Season 2, Episode 24 Jun 17, 2021

In this week’s episode, we will review the role of the hypoxia pathway in regulating neutrophil migration, explore the relationship between endothelial extracellular vesicles and the hemostatic effects of clotting Factor VIIa, and finally look at long-term outcomes with the BTK-inhibitor acalabrutinib in treatment-naive chronic lymphocytic leukemia patients.

Review Series on Platelets and Cancer Jun 10, 2021

Platelets are critical for hemostasis and thrombosis, but recent research highlights their role in many other processes, including inflammation, wound healing, and lymphangiogenesis. In this episode, Drs. José López, Elisabeth Battinelli, Craig Williams, and Owen McCarty discuss the review series on platelets and cancer. The series focuses on the emerging role of platelets in cancer, influencing tumor growth and metastasis, immune evasion, and tumor angiogenesis. The reviews present the current understanding of mutual cross talk between platelets and tumors, communication mediated by RNA transfer and extracellular vesicles, and the potential of antiplatelet agents for cancer treatment.

Review Series on Platelets and Cancer

Season 2, Episode 23 Jun 10, 2021

In this week’s episode, we will review a study demonstrating low rates of response to the Pfizer-BioNTech COVID-19 vaccine among patients with chronic lymphocytic leukemia, review a study looking at associations between post-transplantation cyclophosphamide and cytomegalovirus infection according to donor source, and look at new research indicating that abnormal venous calf muscle pump function in the legs is a risk factor for venous thromboembolism (VTE) and predictor of all-cause mortality.

Season 2, Episode 22 Jun 03, 2021

In this week’s episode, we will review a study in sickle cell disease patients reporting abnormal retention of mitochondria in circulating red cells and elevated mitochondrial DNA in plasma, learn more about the fate of FLT3-ITD clones in AML patients treated with midostaurin, and look at a study showing, for the first time, that selected elderly patients with newly diagnosed multiple myeloma benefit from modification of standard myeloma treatment based on the level of frailty.

Season 2, Episode 21 May 27, 2021

In this week’s episode we will review a phase 1 clinical trial looking at novel fully humanized BCMA-targeting CAR in patients with relapsed or refractory multiple myeloma, discuss a plenary paper reporting that different lymph nodes from patients with follicular lymphoma often have distinct clones, and finally, examine a Letter to Blood reporting high levels of markers of complement activation in plasma during quiescent phases in catastrophic antiphospholipid syndrome patients.

Season 2, Episode 20 May 20, 2021

In this week’s episode, we will examine the prognostic significance of co-mutations in IDH-mutated AML, explore an alternative method of warfarin monitoring, and finally, consider the role of tumor suppressor TP53 in determining response to venetoclax and related agents.

Season 2, Episode 19 May 13, 2021

In this week’s episode, we will review a randomized phase 3 study of patients with high-risk peripheral T-cell lymphoma that compares results from autologous versus allogeneic stem cell transplant during consolidation, look at a report that examines the significance of ABO-incompatible platelet transfusion on outcomes after intracerebral hemorrhage, and learn about how immune dysregulation mediated by tumor interferon signaling and myeloid-derived suppressor cells is associated with CAR-T-cell resistance in large B-cell lymphoma.

Season 2, Episode 18 May 06, 2021

In this week’s episode, we will review a prospective study suggesting that eculizumab discontinuation based on complement genetics is a reasonable and safe strategy in patients with atypical hemolytic uremic syndrome, examine a study that provides new insights into resistance mechanisms and immune evasion in T-cell acute lymphoblastic leukemia, and finally look at a research article describing a new disorder associated with variants in the TLR8 gene that is characterized by neutropenia, infections, lymphoproliferation, B-cell defects, and bone marrow failure.

Season 2, Episode 17 Apr 29, 2021

In this week’s episode, we will review a study that focuses on the morphologic alterations of stored red blood cells, learn more about how T-cell activation profiles distinguish hemophagocytic lymphohistiocytosis and early sepsis, and, finally, look at a report that describes how the WNT signaling pathway is involved in sclerodermatous chronic graft-versus-host disease and can be blocked by available therapeutics.

Season 2, Episode 16 Apr 22, 2021

In this week’s episode, we consider the role of MYC and BCL2 copy number variants in double-hit diffuse large B-cell lymphoma, explore megakaryocyte-biased stem cells in JAK2-mutated myeloproliferative neoplasms, and finally, we look at long-term outcomes with emicizumab prophylaxis in patients with hemophilia, which are even better than in the first reports.

Season 2, Episode 15 Apr 15, 2021

In this week’s episode, we will review a manuscript that describes a novel inherited bone marrow failure syndrome associated with defective clearance of formaldehyde by hematopoietic stem cells, learn about the first large scale analysis of the association between cancer-specific mutations in cancer cells and the incidence of cancer-specific thrombosis, and explore results from a large screening study examining the incidence and progression of monoclonal B cell lymphocytosis in families with an inherited predisposition to chronic lymphocytic leukemia.

Season 2, Episode 14 Apr 08, 2021

In this week’s episode, we discuss recent studies providing new insights on the use of minimal residual disease measurements to guide treatment in patients with high-risk ALL; the increasing risk of venous thromboembolism among patients with cancer; and the use of tocilizumab in the prophylaxis of acute graft versus host disease.

Season 2, Episode 13 Apr 01, 2021

In this week’s episode, we will learn more about the feasibility of combining IDH inhibitors with intensive chemotherapy in patients with newly diagnosed IDH-mutant AML, review a phenotypic and functional analysis of the inflammatory infiltrate in the Langerhans Cell Histiocytosis lesion, and discuss the results of a Phase 3 trial in patients with hemophilia A evaluating prophylactic factor replacement therapy targeting two different Factor VIII trough levels for prevention of bleeds.

Season 2, Episode 12 Mar 25, 2021

In this week’s episode, we look at the role of a previously unidentified variant of DNA methyltransferase 1 as a determinant of beta-thalessemia phenotype, report on the association of vascular thromboembolism in cancer patients treated with immune checkpoint inhibitors, and finally we explore preclinical models of acute erythroid leukemia using CRISPR/Cas 9 hematopoietic genome editing.

Season 2, Episode 11 Mar 18, 2021

In this week’s episode, will review a study that looks at primary diffuse large B-cell lymphoma of the central nervous system comparing tumor biologic features associated with Epstein-Barr virus, examine the functions of regulatory T cells in thrombus resolution in a mouse model, and learn more about subsequent malignant neoplasms in treated pediatric patients with Hodgkin lymphoma.

Season 2, Bonus: How I Treat Series: Acquired Hemolytic Anemia Mar 15, 2021

Diagnosis and treatment of acquired hemolytic anemia can be challenging. In this How I Treat series, edited by Mario Cazzola, clinical experts discuss their approaches to the treatment of patients with 4 different classes of acquired hemolytic anemia.

Season 2, Episode 10 Mar 11, 2021

In this week’s episode, we will review recent studies providing new insights on frontline use of checkpoint inhibitors in classical Hodgkin lymphoma, immune escape mechanisms in diffuse large B-cell lymphoma, and the role of SRP54 mutations in congenital neutropenia.

Season 2, Episode 9 Mar 04, 2021

In this week’s episode, we will review a study that provides further evidence of poor prognosis in patients with multiple myeloma who have “double hit” mutations targeting TP53, examine the early use of BCR-ABL1 kinetics to predict the likelihood of treatment free remission in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors, and learn more about a direct causative link between IL-18 with arrythmias and myocardial fibrosis in sickle cell cardiomyopathy.

Season 2, Episode 8 Feb 25, 2021

In this week’s episode, we will learn more about pre-clinical work that aims to identify optimal immunotargets for treatment of pediatric AML, report on a novel path for subcutaneous administration of Factor 8, and highlight the performance characteristics of the platelet factor 4-dependent p-selectin expression assay for the diagnosis of heparin-induced thrombocytopenia.

Season 2, Episode 7 Feb 18, 2021

In this week’s episode, we will learn about the cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura, review outcomes of a phase 2 trial of pomalidomide in subjects failing prior therapy of chronic graft-versus-host disease, and examine results of a phase 1/2 study looking at the use of ibrutinib and obinutuzimab plus venetoclax in patients with mantle-cell lymphoma.

Season 2, Episode 6 Feb 11, 2021

In this week’s episode, we will cover recent research that provides new insights into the treatment of relapsed or refractory acute myeloid leukemia, immune-mediated thrombotic thrombocytopenic purpura, and sickle cell disease.

Season 2, Episode 5 Feb 04, 2021

In this week’s episode, we will review a study that describes the pathogenic relevance of retinoic acid-responsive CD8+ T-cells in gastrointestinal graft-versus-host disease, learn more about how storage-induced disturbances of platelets is linked to changes in the number and sphingolipid content of platelet extracellular vesicles which predispose to transfusion related acute lung injury, and lastly, review the findings of a phase II study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma.

Season 2, Episode 4 Jan 28, 2021

In this week’s episode, we will explore the characteristics of the tumor and immune environment as predictors of response to blinatumomab in B cell ALL, look at a new predictive tool for guiding decision-making for stem cell transplantation in acute myeloid leukemia, and review the mechanisms of how persistent terminal complement activation can still occur even in the presence of complement inhibitors targeting C3 or C5.

Season 2, Episode 3 Jan 21, 2021

In this week’s episode, we will review a study that shows neutrophils are required for optimum recovery from acute lung injury in a murine model, examine the implication of germline genetic factors in the myeloproliferative neoplasm, polycythemia vera, and learn about the use of emicizumab for bleeding control in a small study of patients with acquired hemophilia A.

Season 2, Episode 2 Jan 14, 2021

This week’s episode covers recent research that provides new insights in erythropoiesis, mastocytosis, and chronic active EBV. First, we’ll review a report describing how interactions between an E3 ubiquitin ligase and a heterochromatin-associated protein may serve as a “toggle” of sorts to regulate the formation of red blood cells. Next, researchers find that presence of hereditary α tryptasemia may predict the risk of severe anaphylaxis in patients with mastocytosis. Finally, we’ll review a report revealing large numbers of myeloid-derived suppressor cells in patients with EBV-associated T/NK cell lymphoproliferative disorders, which may have important implications for understanding disease pathogenesis and targeted approaches to therapy.

Season 2, Episode 1 Jan 07, 2021

In this week’s episode, we will review a study that shows that non-invasive imaging of T cell metabolic activity can detect early graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, learn more about how detailed assessment of measurable residual disease in multiple myeloma can better define outcomes and how treatment resistance arises, and finally, examine the mechanism of action and pharmacokinetics of Ciraparantag, a small molecule being developed to rapidly reverse the effects of anticoagulants.

Season 1, Episode 52 Dec 24, 2020

In this week’s episode, we will review a study that evaluates the role of pre-transplant leukocyte telomere length on survival outcomes in patients with myelodysplastic syndrome, learn more about a potential novel treatment for patients with WHIM syndrome, and examine a novel mechanism important for the maintenance of normal hematopoietic stem cell quiescence, and hence, long-term blood formation.

Season 1, Episode 51 Dec 17, 2020

In this week’s episode, we will learn more about T-cells from SARS-CoV-2-infected individuals, review a study that describes the rapid clinical and histologic response to anti-PD1 first-line therapy in early-stage, unfavorable Hodgkin lymphoma, and discuss a meta-analysis and systematic review of outcomes of patients with hematologic malignancies and Covid-19.

Season 1, Episode 50 Dec 10, 2020

In this week’s episode, we will review a study describing real-world data where PET scans following chemotherapy for primary mediastinal B-cell lymphoma were used to guide consolidative radiotherapy, learn more about the novel role of the BLOC-2 protein complex in the formation of Weibel-Palade bodies that store von Willebrand Factor in endothelial cells, and finally, examine how mutant TP53 in myelodysplastic syndrome is associated with immune checkpoint overexpression in the bone marrow.

Season 1, Episode 49 Dec 03, 2020

In this week’s episode, we will review a study that describes how transfer of whole mitochondria from hematopoietic stem cells to bone marrow mesenchymal stem cells helps regenerate the stroma and its capacity to sustain hematopoietic recovery in irradiated mice undergoing stem cell transplant, examine the potential benefit of adding the BCL2-inhibitor, venetoclax, to standard treatment regimens for patients with relapsed or refractory follicular lymphoma, and finally, we will learn more about how NCOA4, the autophagic receptor for ferritin, is necessary for the mobilization of liver iron stores during stress erythropoiesis.

Season 1, Episode 48 Nov 26, 2020

In this week’s episode, we will review a study that reveals a previously unknown role for the canonical Wnt signaling pathway in the regulation of granulocyte production in steady state and emergency granulopoiesis, examine the discordance in different assays that measure factor VIII activity after adenoviral-associated gene therapy, and learn about the dynamics of declining antibody levels in repeat Covid-19 convalescent plasma donors.

Season 1, Episode 47 Nov 19, 2020

In this week’s episode, we will review an proof-of concept study using the bispecific antibody AFM13 in combination with a check-point inhibitor in patients with relapsed or refractory Hodgkin lymphoma, learn more about how iron restriction might be a promising new therapy for congenital erythropoietic porphyria, and review a manuscript that provides novel molecular insights into the requirement for RUNX1 in a mouse model of inversion 16 acute myeloid leukemia, providing a path forward for new therapies to treat this subgroup of AML.

Season 1, Episode 46 Nov 12, 2020

In this week’s episode, we will review a study on the involvement of lysine-specific, we’ll cover some of the latest findings in COVID-19, multiple myeloma, and myelodysplastic syndromes. First, we’ll review an observational, multicenter study suggesting that convalescent plasma with anti-SARS-CoVid-2 antibodies may be a promising therapy in B-cell depleted patients who have prolonged COVID-19 symptoms. Next, we’ll discuss a research article showing that inhibition of JAK-STAT3 signaling with ruxolitinib could upregulate CD38 expression, thereby enhancing daratumumab-mediated cytotoxicity in multiple myeloma. Finally, we’ll review a report showing for the first time that in MDS, machine learning algorithms can be used to reveal novel associations between morphologic features and genetic lesions that may have important prognostic implications.

Season 1, Episode 45 Nov 05, 2020

In this week’s episode, we will review a study on the involvement of lysine-specific demethylase 1A in hematopoietic stem cell expansion, examine the role of platelet receptor PAR4 in venous thromboembolism; and finally, investigate the relative contributions of maternal versus fetal hepcidin in embryonic iron endowment in both healthy and inflammatory states.

Season 1, Episode 44 Oct 29, 2020

In this week’s episode, we will review a study that uncovers a role for CLCX4 in inducing the two hallmark features of primary myelofibrosis, bone marrow fibrosis and inflammation. We will next examine how genetic predisposition and altered gut microbiome can trigger the development of Precursor B-ALL in mice, and finally, learn how SARS-CoV2 spike proteins activate complement by engaging the alternative pathway, a novel finding which raises the prospect for targeted therapy of COVID-19-associated micro-angiopathy.

Season 1, Episode 43 Oct 22, 2020

In this week’s episode, we will learn more about the immune defects and granule dysfunction in the leukocytes of patients with the rare recessive platelet disorder, gray platelet syndrome, review a study that examines the cost effectiveness of first-line versus third-line ibrutinib in patients with chronic lymphocytic leukemia, and review a manuscript that proposes a diagnostic classifier to facilitate the diagnosis of childhood autoimmune lymphoproliferative syndrome.

Season 1, Episode 42 Oct 15, 2020

In this week’s episode, we will review a study that utilized whole-genome sequencing to define the mutational spectrum and clonal architecture of myelodysplastic/ myeloproliferative neoplasms, learn more about the association between plasma levels of growth differentiation factor 15 and the risk of venous thromboembolism, and examine the role of microenvironment myeloid cells in supporting the growth of T-cell acute lymphoblastic leukemia.

Season 1, Episode 41 Oct 08, 2020

In this week’s episode, we will learn about two molecular brakes that regulate platelet activation and production, review a study showing that giving BCR-ABL1 tyrosine kinase inhibitors after allogeneic stem cell transplantation for Philadelphia-positive ALL prevents relapse, and lastly, see how investigators deciphered the role of a micro-RNA that increases platelet formation by reducing the expression of the actin-bundling protein, L-plastin, in megakaryocytes.

Review Series on Mechanisms and Clinical Implications of Clonal Hematopoiesis Oct 01, 2020

In this bonus episode, we welcome Blood Associate Editor, Dr. Margaret Goodell, along with colleagues Dr. Grant Challen and Dr. David Steensma as they discuss the Blood review series on mechanisms and clinical implications of clonal hematopoiesis. The articles in this series review the mechanisms driving the development of clonal hematopoiesis, the associated risks posed by clonal hematopoiesis for patients with hematologic and nonhematologic disorders and patients with inherited bone marrow syndromes, and the clinical ramifications of discovering clonal hematopoiesis and sharing the results with patients.

Review Series on Mechanisms and Clinical Implications of Clonal Hematopoiesis

Season 1, Episode 40 Oct 01, 2020

In this week’s episode, we will learn more about the pre-clinical and clinical development of optimized, bivalent, tandem CD20 and CD19 chimeric antigen receptor T cells for treatment of relapsed/refractory non-Hodgkin lymphoma, examine a study that reveals the first stage in the clearance of senescent red blood cells by the spleen, and review a manuscript that describes the first transgenic mouse model fully reproducing specific renal lesions and kidney dysfunction observed in human light chain deposition disease.

Season 1, Episode 39 Sep 24, 2020

In this week’s episode, we will learn more about the role of hepcidin in fetal iron homeostasis, review a new study with improved outcomes in HLA-antigen mismatched transplantation, and examine how two splicing factor mutations can coexist in the same cell in patients with myeloid malignancies.

Season 1, Episode 38 Sep 17, 2020

In this week’s episode, we will examine the effects of protecting and regenerating Paneth cells and intestinal stem cells in acute-graft-versus-host-disease, learn more about how Plasmodium falciparum gametocytes develop in the bone marrow by invading erythroblasts, and look at a meta-analysis of direct oral anticoagulants for treating cancer patients with acute venous thromboembolism.

Review Series on Inherited Anemias Sep 10, 2020

In this bonus episode, we welcome Drs. Mario Cazzola, Rachel Grace, and Achille Iolascon as they discuss the Blood Review Series on Inherited Anemias. In this series, experts review the biology and pathophysiology of prominent inherited anemias and provide updated information on their management.

Review Series on Inherited Anemias

Season 1, Episode 37 Sep 10, 2020

In this week’s episode, we start by reviewing two studies on the risks of transmitting HIV from transfusion. The first study asks whether changing the US blood donation policy for men who have sex with men from an indefinite deferral, to a deferral of 12 months from last sex, increases the risk of transfusion-transmitted HIV. The second study examines the frequency of detecting anti-HIV retroviral drugs in the serum of people attempting to donate blood. We will also review a manuscript examining the impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH chemotherapy with or without vorinostat. And lastly, we learn more about platelet hyperactivity in two recent studies of patients with COVID-19.

Season 1, Episode 36 Sep 03, 2020

In this week’s episode, we will learn about vasomotor hyper-responsiveness in sickle cell disease, examine the role of neutrophil extracellular traps in the pathophysiology of immunothrombosis in COVID-19-associated acute respiratory distress syndrome, and discuss a large series evaluating allogeneic hemopoietic cell transplantation in chronic granulomatous disease.

Season 1, Episode 35 Aug 27, 2020

In this week’s episode, we will review a study that identifies a new modular organization of erythropoiesis and offers a novel strategy to overcome chronic anemias, summarize a study that used data from two large phase three trials to examine the risk of thrombosis in patients with newly diagnosed multiple myeloma, and review the first report of autosomal recessive germline TET2 deficiency, which results in immunodeficiency, autoimmune lymphoproliferation, and lymphoma.

Season 1, Episode 34 Aug 20, 2020

In this week’s episode we will review a study exploring recurrent somatic deletions at chromosome 13q12.2 in acute lymphoblastic leukemia leading to upregulation of FLT3, examine how matriptase-2 plays a key role in suppressing hepatic hepcidin expression, and learn about the addition of daratumumab to lenalidomide, bortezomib, and dexamethasone as a quadruple therapy for transplant eligible patients with newly diagnosed multiple myeloma.

Season 1, Episode 33 Aug 13, 2020

In this week’s episode we will review a study exploring the use of demethylating agents in patients with adult T-cell leukemia-lymphoma, learn more about hematopoietic stem cell formation, and examine treatment timing and prognosis in newly diagnosed patients with acute myeloid leukemia.

Season 1, Episode 32 Aug 06, 2020

In this week’s episode we will review a study exploring the use of a novel hemophilia A mouse model to examine emicizumab function in vivo, a new approach to fighting the cytokine storm of HLH with a combination of glucocorticoids and ruxolitinib, and a timely Letter to Blood about red cell-bound antibodies and transfusion requirements in hospitalized patients with COVID-19.

Season 1, Episode 31 Jul 30, 2020

In this week's episode we will review a study that demonstrates how the impaired hematopoietic stem cells (HSCs) observed in β-thalassemia can be rescued by administration of parathyroid hormone, learn more about genetic variants that can increase the risk of venous thromboembolism, and explore the identification of two DNA methylation subtypes of Waldenström’s macroglobulinemia.

Season 1, Episode 30 Jul 23, 2020

In this episode we will review a study identifying cyclin-dependent kinase 6 (or CDK6) as a therapeutic target of NUP98-driven acute myeloid leukemia (or AML), learn more about the largest clinical dataset on cold agglutinin disease, and examine the effects of COVID-19 on coagulation parameters as well as bleeding and thrombosis in hospitalized patients.

Season 1, Episode 29 Jul 16, 2020

In this episode we’ll review the risk of bleeding after initiating treatment for acquired hemophilia A, examine the functional effect of antibodies leading to immune TTP and how this can be used as a biomarker, and finally, a blast from the past – we will discuss a study that explores the intriguing possibility that a core component driving globin gene expression became active long ago.

Season 1, Episode 28 Jul 09, 2020

This week we’ll review data that suggests the pro-inflammatory environment associated with aging alters hematopoietic stem cell function by inducing IL27 receptor alpha expression, examine a study attempting to optimize antiplatelet therapy in essential thrombocythemia, and learn more about a study by investigators who have proposed that myelodysplastic syndrome patients with mutations in SF3B1 identify a new subtype of that disease.

Review Series on Secondary Leukemia Jul 02, 2020

In this bonus podcast episode Dr. Jean Soulier shares highlights of the Blood Review Series on Secondary Leukemia. In this review series, experts provide new insights into the pathobiology of secondary acute myeloid leukemias arising in diverse genetic or acquired, benign or malignant hematologic disorders.

Review Series on Secondary Leukemia

Season 1, Episode 27 Jul 02, 2020

This week we will explore the impact of calreticulin (or CALR) haploinsufficiency on hematopoietic stem cell activity in the context of myeloproliferative neoplasms, explore mechanisms of leukemogenesis related to the E2A-PBX1 fusion protein in childhood B-cell acute lymphoblastic leukemia, and learn about the connection between intestinal microbiota, their metabolite short chain fatty acids and chronic graft versus host disease after allogeneic stem cell transplantation.

Season 1, Episode 26 Jun 25, 2020

In this week’s episode we’ll examine the cause and clinical significance of dysplastic hematopoiesis at time of diagnosis in patients with multiple myeloma, review a multi‐omics analysis of patients that have undergone blastic transformation of chronic myeloid leukemia, and learn about HLA alleles that are either risk factors or protective for immune-mediated TTP in Japan.

Season 1, Episode 25 Jun 18, 2020

In this week’s episode we’ll review a study focusing on the causes and impact of the inflammation of aging on hematopoietic stem cell function, learn about the potential influence of the endothelial cell protein C receptor in the pathogenesis of hemophilic arthropathy, and assess a novel function of GPS2 on erythropoiesis.

Season 1, Episode 24 Jun 11, 2020

In this week’s episode we’ll review results of a trial of venetoclax plus low-dose cytarabine in untreated patients with acute myeloid leukemia who are ineligible for intensive chemotherapy, learn how HRI-regulated transcription factor ATF4 activates BCL11A transcription to silence fetal hemoglobin expression, and assess new data demonstrating that aromatase is a novel neosubstrate of cereblon responsible for thrombocytopenia caused by immunomodulatory drugs.

Season 1, Episode 23 Jun 04, 2020

This week’s episode will discuss the impact of sickle cell disease on the bone marrow vascular niche, highlight more about the evolution of retrovirus-infected premalignant T-cell clones in adult T-cell leukemia/lymphoma, and assess the outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome.

Season 1, Episode 22 May 28, 2020

In this week’s episode we will review a report on the use of hydroxyurea as an alternative to transfusion therapy for the prevention of recurrent strokes in patients with sickle cell anemia, learn more about why some erythroblasts continue to produce hemoglobin F in adults, and review a study that explores cancer outcomes in patients with short telomere syndromes.

Season 1, Episode 21 May 21, 2020

Today we’ll review data on the high frequency of germline RUNX1 mutations in patients with acute myeloid leukemia, learn more about the development of an international prognostic score that predicts time to first treatment in CLL patients with early, asymptomatic disease, and explore the possibility of improving the activity of virus-directed immunotherapies against certain types of EBV tumors.

Season 1, Episode 20 May 14, 2020

In this week’s episode we’ll learn why anticoagulation may play a role in the prevention of vaso-occlusive events in sickle cell disease, review data that could help predict the risk of VTE and bleeding in hospitalized patients, and find out if Ruxolitinib is a viable treatment of steroid-refractory acute graft-versus-host disease.

Season 1, Episode 19 May 07, 2020

This week’s episode will review a report on a new mouse model with an enhanced ability to support human hematopoietic and tumor engraftment, explore more about increased mTOR activation in idiopathic multicentric Castleman disease, and assess the feasibility and efficacy of CD19-targeted CAR-T cells with concurrent ibrutinib for CLL.

Season 1, Episode 18 Apr 30, 2020

This week’s episode will review the incidence and fate of clonal hematopoiesis among donors and recipients of related allogeneic hematopoietic stem cell transplantation, examine the manifestations and clinical course of patients with a particular subtype of Fanconi anemia, and assess three clinical studies that demonstrate high rates of efficacy and low rates of toxicity of daratumumab in patients with previously treated AL amyloidosis.

Season 1, Episode 17 Apr 23, 2020

This week’s episode will highlight the development of a factor VIII replacement therapy for patients with severe Hemophilia A, examine a novel pathway of resistance of FLT3-ITD+ AML cells to FLIT3 inhibitors, and review long-term results of a pilot study in children with low risk B-cell ALL conducted in a limited-resource setting.

Review Series on Rare Systemic Hematologic Disorders Apr 16, 2020

In this bonus podcast episode, Drs. Nancy Berliner and Laurie Sehn lead a discussion on this series of authoritative reviews on a collection of rare systemic hematologic disorders that are frequently difficult to recognize, diagnose, and treat. The series highlights new genomic and proteomic insights that inform our understanding of their pathophysiology and treatment.

Review Series on Rare Systemic Hematologic Disorders

Season 1, Episode 16 Apr 16, 2020

This week’s episode will review evidence that selecting donors with specific types of natural killer cells leads to improved outcome in stem cell transplantation, review an analysis of platelet transfusion in cerebral hemorrhage, and explore the challenges of diagnosing recurrent ipsilateral deep vein thrombosis.

Season 1, Episode 15 Apr 09, 2020

This week’s episode will examine data on the impact of the FDG uptake level on predicting subsequent high-grade histological transformation in follicular lymphoma, explore clonal tracking in gene therapy patients as a method for understanding human hematopoiesis, and review a study on the recognition of platelet factor 4-von Willebrand factor complexes by heparin-induced thrombocytopenia antibodies as a basis for the pathogenesis of HIT.

Season 1, Episode 14 Apr 02, 2020

In this week’s episode we’ll learn about novel insights into the link between innate immune responses and activation of coagulation during gram-negative sepsis, examine the impact of GPRASP proteins on hematopoietic stem cell transplantation, and explore the dynamics of clonal hematopoiesis in anemia of older individuals.

Season 1, Episode 13 Mar 26, 2020

This week’s episode will review data on spliceosomal gene mutations, evaluate the impact of Ruxolitinib on weight gain, and assess the effect of compliment blockade with eculizumab on high risk patients with stem cell transplant associated thrombotic microangiopathy.

Season 1, Episode 12 Mar 19, 2020

This week’s episode will review the clinical correlates of NT5C2 mutations in relapsed ALL, the impact of Crovalimab, a recycling monoclonal antibody against complement component C5 in paroxysmal nocturnal hemoglobinuria, and the relationship between leukocyte NADPH oxidase and leukotriene B4 and neutrophilic inflammation in the context of chronic granulomatous disease

Season 1, Episode 11 Mar 12, 2020

This week’s episode will review a novel treatment for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis, learn more about the behavior of leukemic clones in patients with acute myeloid leukemia receiving venetoclax-based combination therapies, and review the role of the integrin alpha9beta1 in arterial thrombosis.

Season 1, Episode 10 Mar 05, 2020

This week's episode will explore interventions that may improve outcomes in sepsis by stabilizing neutrophil extracellular traps, or NETs, discuss the use of a novel strategy to generate CAR T cells that react with surface antigens on AML cells, and review data about how chronic lymphocytic leukemia cells become resistant to Venetoclax.

Review Series on Understanding and Treating Primary Immunodeficiency Feb 27, 2020

In this episode Dr. Catherine Bollard, Blood Associate Editor provides highlights of this commissioned review series Understanding and Treating Primary Immunodeficiency, that highlights cutting-edge developments in the biology and management of primary immune deficiencies.

Review Series on Understanding and Treating Primary Immunodeficiency

Season 1, Episode 9 Feb 27, 2020

This week's episode will review efforts to improve the activity of CAR T cells, explore the impact of Protein C activator AB002 on thrombus development, and look at results from a UK study on minimal residual disease status and outcome after transplantation in NPM1-mutated AML.

Season 1, Episode 8 Feb 20, 2020

This week’s episode will examine how graft versus host disease in the colon is driven by an inflammatory cytokine produced by specialized donor T cells, review a prospective, multicenter study to assess the frequency and clinical relevance of low level mutations in chronic myeloid leukemia, and learn about a potential new therapeutic that blocks the activity of the iron-regulatory hormone Erythroferrone to reduce iron overload in thalassemia.

Season 1, Episode 7 Feb 13, 2020

This week’s episode will review treatment for secondary prevention of venous thromboembolism in children, a therapeutic strategy for relapsed or refractory B-cell acute lymphoblastic leukemia, Ivosidenib monotherapy in patients with newly diagnosed AML with mutations in the isocitrate dehydrogenase 1 gene, and survival outcomes of chronic Lymphocytic Leukemia patients treated with Ibrutinib.

Season 1, Episode 6 Feb 06, 2020

This week’s episode will examine the critical role of platelet necrosis in ischemic stroke injury, the discovery of the molecular basis for the PEL blood group, and the impact of NPM1/FLT3-ITD genotypes in patients with acute myeloid leukemia.

Review Series on Treatment of Venous Thrombotic Disorders Jan 31, 2020

In this episode we welcome Drs. Thomas Ortel, Jeffrey Weitz, and Kenneth Bauer as they discuss the Blood Review Series on the Treatment of Venous Thrombotic Disorders. In this review series, experts contribute 6 seminal reviews that focus on the treatment of venous thromboembolism (VTE) in adults and children, the management of VTE developing in unusual locations and in the setting of thrombophilia, and new targets and antithrombotic therapies in development.

Review Series on Treatment of Venous Thrombotic Disorders

Season 1, Episode 5 Jan 30, 2020

In this episode we’ll examine a new strategy to improve the durability of remission after CAR T-cell therapy for pediatric B cell leukemia, explore the genomic landscape of Breast Implant-Associated Anaplastic Large Cell Lymphomas, and discuss a new report showing that the occurrence of arterial thrombotic events following the diagnosis of myeloproliferative neoplasms is associated with a significantly increased risk of a second cancer.

Season 1, Episode 4 Jan 23, 2020

Today we’ll examine the role of heredity vs. environmental factors in the evolution of age-related clonal hematopoiesis, review the first systematic approach to uncover all possible activating point mutations within and around the transmembrane domain of the thrombopoietin receptor in myeloproliferative neoplasms, and discuss the role of complement activation and mutations in complement regulatory genes in patients with thrombotic or catastrophic antiphospholipid syndromes.

Season 1, Episode 3 Jan 16, 2020

In this episode we highlight the development of intensified T-cell acute lymphoblastic leukemia-focused protocols, the use of a thrombopoietin agonist for thrombocytopenia following allogeneic hematopoieticstem cell transplantation, and a crucial step forward in the development of miRNA therapies targeting myeloid diseases.

Season 1, Episode 2 Jan 09, 2020

This episode will explore the consequences of a loss of the interaction between mutant calreticulin and another ER resident protein, and how this may promote myeloproliferative neoplasms, the role of a calcium-induced transcription factor in driving diffuse large B-cell lymphoma signaling, and a comparison of two therapies for standard risk acute graft-versus-host disease.

Season 1, Episode 1 Jan 02, 2020

This episode will highlight a unique treatment for refractory hematologic malignancies, therapy-induced mutations impacting the genomic landscape of relapsed acute lymphoblastic leukemia, and a unique approach to avoiding chronic graft-versus-host disease.

Sneak Peek Episode 2 Dec 10, 2019

This episode highlights articles and commentaries that help expand our understanding of prognostic biomarkers in CLL, learn more about a streamlined analysis of the granulocyte transcriptome in myeloproliferative neoplasms, explore the role of neutrophil extra cellulartraps in adenosine deaminase deficiency, and examine the function of the plant homeodomain-like finger protein 6, in hematopoietic stem cell self-renewal.

Sneak Peek Episode 3 Dec 10, 2019

This episode discusses the immune engine in classical Hodgkin Lymphoma, osteopontin’s keyrole in the chemoattraction of neutrophils in transfusion-related acute lunginjury,B-1 progenitor acute lymphoid leukemia, and exciting new ideas for heparin-induced thrombocytopenia treatment.

Sneak Peek Episode 4 Dec 10, 2019

The topics in this episode include studies on the mechanism of progression in myelodysplastic syndromes, the value of gait speed as a predictor of outcomes in older adults with hematologic malignancies, the role of extended eltrombobag therapy on severe aplastic anemia, and the role of the Hedghog pathway mutations in chronic lymphocytic leukemia.

Sneak Peek Episode 1 Dec 10, 2019

This episode explores four compelling topics which include: Hemophagocytic Lymphohistiocytosis, a severe and potentially fatal systemic inflammatory syndrome, CAR T-cell therapy in follicular lymphomas, Sickle Cell Anemia and sickle trait in thrombosis, and mutated calreticulin in myeloproliferative disorders.

Blood Podcast - Trailer Nov 09, 2019

The article highlighted in this trailer "The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells" was published June 6, 2019; Blood, Volume 133, Issue 23.

The authors of this article are: Satoru Miyagi , Patrycja Sroczynska , Yuko Kato , Yaeko Nakajima-Takagi , Motohiko Oshima , Ola Rizq , Naoya Takayama , Atsunori Saraya , Seiya Mizuno , Fumihiro Sugiyama , Satoru Takahashi , Yumi Matsuzaki , Jesper Christensen , Kristian Helin , Atsushi Iwama.

Our TOPPODCAST Picks

Follow Us

Stay Connected

Related Podcasts

Links

Stay Connected