Blood Podcast

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

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

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

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 m...

Review Series on RNA Therapeutics in Hematology

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

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

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

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 hematopoiet...

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.

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

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 refr...

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

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

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

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

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

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 II complexes in 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

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

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

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

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 ...

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

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 associat...

Review Series on Hematopoietic Stem Cells

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

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

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

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

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

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

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

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?

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

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

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

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

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.