Explorez tous les épisodes du podcast Blood Podcast

In this How I Treat Series episode Dr. Thomas Ortel leads a discussion with author Dr. Patrick Foy on his paper “How I diagnose and treat thrombocytopenia in geriatric patients”.

See the full How I Treat series on geriatric hematology in volume 143 issue 3 of Blood Journal.

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

Featured Articles:

• Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome
• Cyclophosphamide mitigates non-ICANS neurotoxicities following ciltacabtagene autoleucel treatment
• Enhanced α2-3–linked sialylation determines the extended half-life of CHO-rVWF

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

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

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. 

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 

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. 

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.

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. 

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.

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.

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. 

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.

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

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

Featured Articles:

• Salvage autologous transplant in relapsed multiple myeloma: long-term follow-up of the phase 3 GMMG ReLApsE trial
• DDAVP response and its determinants in bleeding disorders: a systematic review and meta-analysis
• Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of diffuse large B-cell lymphoma

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. 

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.

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).

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.

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.

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.

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. 

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.

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.

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

Featured Articles:

• IL-1R1 and IL-18 signals regulate mesenchymal stromal cells in an aged murine model of myelodysplastic syndromes
• Targeting cell-surface VISTA expression on allospecific naïve T cells promotes tolerance
• Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial

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.

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.

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.

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.

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.

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.

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.  

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.

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.

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

Review Series on Classical Myeloproliferative Neoplasms

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

Featured Articles:

• Aging platelets shift their hemostatic properties to inflammatory functions
• Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: primary analysis of the ELM-1 study
• Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma

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.

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.

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

Review Series on Germ Line Predisposition to Hematologic Malignancy

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.

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.

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.

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.

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.

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

Review Series on Banked Allogeneic Immune Effector Cells

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.

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

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. 

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.

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.