Blood Podcast

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.