Blood Podcast

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:

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:

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:

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

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.

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, your source for innovative ideas and cutting-edge information. In this episode Associate Editor, Dr. John Crispino discusses the Review Series on Hematopoietic Stem Cells with authors, Dr. David Kent and Dr. Jennifer Trowbridge.

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.

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.

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.

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.

Blood 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.

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.

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.

Blood 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.

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.

Blood 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.

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.

Season 2, Bonus: Blood 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.

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.

Season 1, Bonus: Blood 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.

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.

Season 1, Bonus: Blood 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.

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.

Season 1, Bonus: 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.

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.

Season 1, Bonus: Blood 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.

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.

Season 1, Bonus: Blood 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.

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.

Season 1, Bonus: Blood 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.

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 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.

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.

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.

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