Blood Podcast

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

In part two of the How I Treat Series on Transfusion Medicine Dr. Erica Wood interviews the "How I Manage Major Hemorrhage" author group: Drs. Jeannie Callium, Keyvan Karkouti, and Ron George.Find the full published review series in Volume 145 Issue 20 of Blood Journal.

In this week's episode we'll learn about how frequent blood donation affects clonal hematopoiesis in older, male blood donors; the effect of immune microenvironment on response to bispecific antibodies in diffuse large B-cell lymphoma; and the feasibility of adding blinatumomab to early consolidation therapy in CD19-positive Ph-negative B-cell acute lymphoblastic lymphoma.Featured ArticlesClonal Hematopoiesis Landscape in Frequent Blood DonorsIntegrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody responseUpfront Blinatumomab Improves MRD Clearance and Outcome in Adult Ph-negative B-lineage ALL: The GIMEMA LAL2317 Phase 2 Study

In this two-part series, Dr. Erica Wood talks with Drs. Masja de Haas, Helen Savoia, and Stella Chou about their articles in the How I Treat Series on Transfusion Medicine. Topics include noninvasive prenatal testing for red blood cell and platelet antigens, transfusion cases in sickle cell disease, and pregnant patients who are alloimmunized to RBC antigens. Find the full published review series in Volume 145 Issue 20 of Blood Journal.

In this week's episode, we'll learn about stopping myeloma maintenance therapy in the modern era. New research suggests that many patients in remission can discontinue lenalidomide, remaining treatment-free, without jeopardizing disease response. After that: a novel congenital neutropenia syndrome. Mutations in the COPZ1 gene impact myeloid differentiation and development of neutropenia. Researchers describe the mechanisms and propose a treatment strategy for restoring granulopoiesis. Finally, ruxolitinib maintenance therapy after allogeneic transplant. In a phase 2 study, this treatment strategy was associated with low rates of chronic graft-versus-host disease. Investigators say the use of JAK inhibitors in this context warrants further study.Featured Articles: Sustained bone marrow and imaging MRD negativity for 3 years drives discontinuation of maintenance post-ASCT in myelomaA new severe congenital neutropenia syndrome associated with autosomal recessive COPZ1 mutationsLow rates of chronic graft-versus-host disease with ruxolitinib maintenance following allogeneic HCT

In this week's episode, we'll learn more about how measurable residual disease might help guide decisions about post-transplant gilteritinib maintenance in FLT3-ITD acute myeloid leukemia, or AML; how stemness contributes to chemotherapy resistance in AML; and effects of babesiosis on red blood cells from individuals with sickle cell disease, sickle cell trait, and wild-type hemoglobin. Featured Articles:Measurable residual disease and post-transplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia Babesiosis and Sickle Red Blood Cells: Loss of Deformability, Heightened Osmotic fragility and Hyper-vesiculation 

In this week's episode, we'll hear about how researchers look toward the lung, and find uniquely programmed blood stem cells. This study is the first to fully characterize hematopoietic stem and progenitor cells in the adult human lung. After that: researchers develop a neural network-based probabilistic classifier, DLBclass, that assigns all diffuse large B-cell lymphomas into one of five genetic subtypes. It's an inclusive taxonomy that they say provides actionable genetic information in almost all patients with DLBCL. Finally, new insights on NETS, or neutrophil extracellular traps. In the liver vasculature, NET removal leads to secondary inflammation, resulting in new waves of NETS that may impact future infection. We'll review these and other findings from this recent mouse model study.Featured Articles:Decoding functional hematopoietic progenitor cells in the adult human lungDLBclass: a probabilistic molecular classifier to guide clinical investigation and practice in diffuse large B-cell lymphomaDonor regulatory T-cell therapy to prevent graft-versus-host disease

In this week's episode we'll learn more about how phosphoseryl-tRNA kinase inhibition promotes cell death in acute myeloid leukemia, or AML; APOE gene variants and their association with post-hematopoietic stem cell transplant outcomes in AML; and pathways by which chronic inflammation and oxidative stress may lead to cardiomyopathy in patients with sickle cell disease.Featured Articles:PSTK inhibition activates cGAS-STING, precipitating ferroptotic cell death in leukemic stem cells Common Hereditary Variants of the APOE Gene and Posttransplant Outcome in Acute Myeloid Leukemia 17R-Resolvin D1 Protects Against Sickle Cell Related Inflammatory Cardiomyopathy in Humanized Mice 

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 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 trialDDAVP response and its determinants in bleeding disorders: a systematic review and meta-analysisTargeting DOT1L and EZH2 synergizes in breaking the germinal center identity of diffuse large B-cell lymphoma

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 syndromesTargeting cell-surface VISTA expression on allospecific naïve T cells promotes toleranceEpcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial

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 functionsOdronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: primary analysis of the ELM-1 studyDissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma

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 learn more about using itacitinib for the prevention of graft vs host disease in haploidentical transplants, diagnosis and management of purpura fulminans, and results of a systematic review seeking evidence for sickle cell crisis-associated mortality in individuals with sickle cell trait. Featured Articles:Itacitinib for prevention of graft-versus-host disease and cytokine release syndrome in haploidentical transplantationHow I diagnose and treat acute infection–associated purpura fulminansSickle cell trait does not cause “sickle cell crisis” leading to exertion-related death: a systematic review

In today's episode, we'll discuss time-limited triplet therapy in relapsed or refractory CLL. Zanubrutinib, venetoclax and obinutuzumab induced deep remissions, and was well tolerated, even in very high-risk patients, and those with prior exposure to targeted therapies. After that: researchers chronicle the development of a patient-reported outcome measure for sclerosis associated with chronic GVHD—graft-versus-host disease. The new symptom scale—currently undergoing validation studies—may provide valuable information regarding severity, functional impact, and response to therapy. Finally, a study of changes in population dynamic rates that underlie inflammation-associated myeloid bias. The work demonstrates the use of mathematical models to deliver critical biological insights and uncover underlying mechanisms.Featured Articles:MRD-guided zanubrutinib, venetoclax, and obinutuzumab in relapsed CLL: primary end point analysis from the CLL2-BZAG trialDevelopment of the Lee Symptom Scale–Skin Sclerosis for chronic GVHD–associated sclerosisPopulation dynamics modeling reveals that myeloid bias involves both HSC differentiation and progenitor proliferation biases

In this week's episode we'll learn more about azacitidine-venetoclax combination therapy for first-line treatment of high-risk myelodysplastic syndromes; a new risk-scoring system for post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia, also known as B-ALL; and a novel mechanism for inotuzumab ozogamicin resistance in B-ALL.Featured Articles:Efficacy and safety of venetoclax plus azacitidine for patients with treatment-naive high-risk myelodysplastic syndromesDevelopment of ALL-Hematotox: predicting post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemiaDNTT-mediated DNA damage response drives inotuzumab ozogamicin resistance in B-cell acute lymphoblastic leukemia

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

In this week's episode we'll learn more about the significance of hypercalcemia in monoclonal gammopathy of undetermined significance, the role of neutrophil gelatinase-associated lipocalin in hemostasis, and the feasibility of combining CD19-targeted NK- or T-cell therapy with anti-CD19 monoclonal antibodies.Featured Articles:Approaching Hypercalcemia in Gammopathy of Undetermined Significance: Insights from the iStopMM study Deficiency of neutrophil gelatinase-associated lipocalin elicits Hemophilia-like bleeding and clotting disorder Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis 

In this Review Series episode Reflections on a Quarter Century of TKIs in CML introduced by Associate Editor Dr. Jason Gottlieb, we'll hear from contributing authors Drs. Brian Drucker, Francois Guillot, Tim Hughes and Michael Deininger, as they discuss how CML treatment has been impacted since the introduction of tyrosine kinase inhibitors 25 years ago.Click here to view the complete Review Series featured in Volume 145 Issue 9 of Blood.

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

In this week's episode we'll find out about longer term results from a pivotal trial of mosunetuzumab in relapsed/refractory follicular lymphoma, potential use of CD70 CAR T-cells that secrete an anti-CD33/anti-CD3 bispecific antibody as a therapy for acute myeloid leukemia, and how ferroptosis regulates hemolysis in stored red blood cells.Featured Articles:Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapiesCD70 CAR T cells secreting an anti-CD33/anti-CD3 dual-targeting antibody overcome antigen heterogeneity in AMLFerroptosis regulates hemolysis in stored murine and human red blood cells

In this Review Series episode on Basic/Translational Science of Factor VIII, Factor IX, and von Willebrand Factor introduced by Dr. Thomas Ortel, we'll hear from contributing authors Drs. Ben Samuelson Jones, Mac Monroe and Peter Lenting as they discuss how the functional roles of these 3 proteins are interconnected. Click here to view the complete Review Series featured in Volume 144 Issue 21 of Blood.

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

In this week's episode we'll learn more about a phase 2 trial of first-line zanubrutinib, obinutuzumab, and venetoclax in TP53-mutated mantle cell lymphoma; early development of hyperdiploidy in multiple myeloma; and a phase 1 trial of the asparaginase pegcrisantaspase plus venetoclax in relapsed/refractory acute myeloid leukemia.Featured Articles:Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutationDevelopment of hyperdiploidy starts at an early age and takes a decade to completeA phase 1 study of the amino acid modulator pegcrisantaspase and venetoclax for relapsed or refractory acute myeloid leukemia

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

In this Review Series episode on Globin Disorders introduced by Drs. Thomas Coates and Irene Roberts, we'll hear from Dr. Douglas Higgs and Dr. Mitchell Weiss as they address advances in our understanding of globin gene biology.Click here to view the complete Review Series featured in Volume 144 Issue 8 of Blood.

In this week's episode we'll learn more about an experimental regimen for classical Hodgkin lymphoma that combines brentuximab vedotin, nivolumab, and chemotherapy; a possible role for type 1 interferon signaling in developing autoantibodies to red blood cells in sickle cell disease; and how genomic alterations affecting class I human leukocyte antigen molecules may affect patients with cutaneous T-cell lymphoma. Featured Articles:Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphomaIFN-I promotes T-cell–independent immunity and RBC autoantibodies via modulation of B-1 cell subsets in murine SCDGenetic alteration of class I HLA in cutaneous T-cell lymphoma

In this week's episode we'll learn about the role of iron in myelodysplastic syndromes, or MDS. After that: long-term treatment outcomes in immune thrombocytopenia from the STOPAGO study.  Finally, new insights into APL treatment outcomes and prognostic factors from the large-scale Harmony APL project which used ATRA-Arsenic combination therapy.Featured Articles:Genetic iron overload aggravates, and pharmacological iron restriction improves, MDS pathophysiology in a preclinical studyLong-term follow-up of the STOPAGO studyAcute promyelocytic leukemia: long-term outcomes from the HARMONY project

In this week's episode, we'll learn about the prevalence and impact of dexamethasone dose reductions during triple or quadruple therapy for newly diagnosed multiple myeloma, a conditional knockout mouse model for testing gene therapy in X-linked sideroblastic anemia, and real-world efficacy and safety of ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma.Featured Articles:Dexamethasone dose intensity does not impact outcomes in newly diagnosed multiple myeloma: a secondary SWOG analysisAn erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSASafety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma

In this week's episode, we'll be comparing BTK inhibitors in relapsed/refractory CLL. Then, we'll hear how researchers in the UK unraveled the genetic background of the AnWj blood group.  Finally we'll learn about the role of BCL-2 and BAFF in CLL cell survival following venetoclax therapy. Featured Articles:Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotypeSustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINEVenetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia

In this week's episode, we'll learn more about mechanisms of primary resistance to BCMA-targeted bispecific T-cell engagers in relapsed/refractory multiple myeloma, the effects of emapalumab therapy on outcomes in patients with pediatric hemophagocytic lymphohistiocytosis who receive stem cell transplants, and a cell death process that may help account for increased thromboembolic risk in patients receiving cancer chemotherapy.Featured Articles:Impact of soluble BCMA and non–T-cell factors on refractoriness to BCMA-targeting T-cell engagers in multiple myelomaEmapalumab therapy for hemophagocytic lymphohistiocytosis before reduced-intensity transplantation improves chimerismGSDME-mediated pyroptosis contributes to chemotherapy-induced platelet hyperactivity and thrombotic potential

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

In this week's episode we'll learn more about how clonal hematopoiesis affects prognosis in patients with telomere biology disorders, consider recently uncovered molecular subtypes of extracutaneous juvenile xanthogranulomas, and discuss a clinical trial of the BCMA-CD3 bispecific antibody teclistamab in patients with relapsed/refractory multiple myeloma who have received previous BCMA-targeted therapy.Featured Articles:Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutationsRecurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissueEfficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies

In this week's podcast, we'll learn about targeting mutant calreticulin in MPNs, or myeloproliferative neoplasms. Then, it's time to address bleeding and clotting in cancer. Results of the prospective, observational CAT-BLED study provide much needed data on the high risk of clinically relevant bleeding, and its association with all-cause mortality, among cancer patients receiving systemic therapy. Finally, we'll revisit diagnostic guidelines for familial HLH, or hemophagocytic lymphohistiocytosis. The authors present new and improved diagnostic criteria with revised clinical criteria, and guidelines on cellular and genetic diagnostic assays.Featured Articles:Selective targeting of mutated calreticulin by the monoclonal antibody INCA033989 inhibits oncogenic function of MPNBleeding events in patients with cancer: incidence, risk factors, and impact on prognosis in a prospective cohort studyDiagnostic guidelines for familial hemophagocytic lymphohistiocytosis revisited

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.

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:Genetic Risk Stratification and Outcomes Among Treatment-Naive Patients with AML Treated With Venetoclax and Azacitidine Daratumumab in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma: DELPHINUS Study Genetic Engineering of Transfusable Platelets with mRNA-Lipid Nanoparticles is Compatible with Blood Banking Practices  

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:Spatial transcriptomics reveals profound subclonal heterogeneity and T-cell dysfunction in extramedullary myelomaRuxolitinib for pediatric patients with treatment-naïve and steroid-refractory acute graft-versus-host disease: the REACH4 studyYAP1 regulates thrombopoiesis by binding to MYH9 in immune thrombocytopenia

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 ArticlesAsciminib Monotherapy as Frontline Treatment of Chronic Phase Chronic Myeloid Leukaemia - Results from the ASCEND StudyRisk Prediction for Clonal Cytopenia: Multicenter Real-World Evidence Genotyped RhD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D 

In this week's episode we'll learn about the updated phase 3 results on fixed-dose venetoclax plus obinutuzumab in previously untreated CLL. Then, we'll hear about dual epi-immunotherapy in classical Hodgkin lymphoma. Finally we'll explore redefining risk of treatment failure in CML.Featured Articles:Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 studyEpigenetic agents plus anti-PD-1 reprogram the tumor microenvironment and restore antitumor efficacy in Hodgkin lymphomaA predictive model for therapy failure in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy

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:Germ line ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predispositionCoagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivoProposals for revised International Working Group–European LeukemiaNet criteria for anemia response in myelofibrosis

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:Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic targetInfluence of TP53 gene mutations and their allelic status in myelodysplastic syndromes with isolated 5q deletionA phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia

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 NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup ofpatientsUse of HSC-targeted LNP to generate a mouse model of lethal α-thalassemia and treatment via lentiviralgene therapyMolecular taxonomy of myelodysplastic syndromes and its clinical implications

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: Critical role of tripartite fusion and LBD truncation in certain RARA- and all RARG-related atypical APLManagement of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchangeHope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation (a national multicenter study)

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:Fixed-duration pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL: Phase 1b BRUIN trialMurine models of erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxineTargeting PKCα alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin

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: Outcomes of hematopoietic stem cell transplantation in 813 pediatric patients with Fanconi anemiaFoxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasisClinical networking results in continuous improvement of the outcome of patients with acute promyelocyticleukemia

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:CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemiaATM germ line pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematologicalmalignanciesPreclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) inKMT2A- and NPM1-altered leukemias

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 ArticlesHA-1–targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem celltransplantation4D intravital imaging studies identify platelets as the predominant cellular procoagulant surface in a mousehemostasis modelRandomized study of induction with bendamustine-rituximab ± bortezomib and maintenance withrituximab ± lenalidomide for MCL

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: Outcomes of younger patients with mantle cell lymphoma experiencing late relapse (>24 months): the LATE-POD studyMass spectrometry–based assessment of M protein in peripheral blood during maintenance therapy inmultiple myelomaIn vivo CAR T-cell generation in nonhuman primates using lentiviral vectors displaying a multidomain fusion ligand

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: Introduction to a review series on factor XIBiology of factor XITargeting factor XI and factor XIa to prevent thrombosisFactor XI deficiency: phenotypic age-related considerations and clinical approach towards bleeding risk assessment

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: Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblasticleukemiaGVHD targets organoid-forming bile duct stem cells in a TGF-β–dependent mannerSeven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses andtreatment-free remissions

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:Iron, hemochromatosis genotypes, and risk of infections: a cohort study of 142 188 general population individualsMolecular, clinical, and therapeutic determinants of outcome in NPM1-mutated AMLCD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models