Blood Podcast: Recent Episodes
American Society of Hematology
The Blood Podcast summarizes content recently published in Blood the most cited peer-reviewed publication in the field of hematology.
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.
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, your source for innovative ideas and cutting-edge information. In this episode Associate Editor, Dr. John Crispino discusses the Review Series on Hematopoietic Stem Cells with authors, Dr. David Kent and Dr. Jennifer Trowbridge.
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 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.
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.
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.
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.
In this week's podcast, we’ll focus on 2 reports on clinical outcomes following COVID-19 vaccination in patients with hematologic malignancies. Despite full or partial vaccination, these patients have an increased risk of poor outcomes compared to matched controls or the general population. In a third report, we discuss new data on HLA-mismatching and outcomes of haploidentical transplants.
In this week's podcast, we’ll compare the efficacy of autologous stem cell transplant to CAR T-cell therapy for relapsed diffuse large B-cell lymphoma, learn more about a novel subtype of hemochromatosis caused by constitutional PIGA mutations, and discuss the findings from a phase 2 trial of obinutuzumab, ibrutinib and venetoclax in patients with untreated high-risk CLL.
In this week's podcast, we’ll look at work from researchers who found pathogenic or likely pathogenic variants of cancer predisposition genes in nearly 14% of adults with AML. Next, we’ll review research demonstrating that a recently identified series of resolvins reduces neutrophil extracellular trap formation and enhances clearance of these NETs by macrophages, suggesting a new mechanism for the resolution of inflammation and coagulopathies associated with various infections. We’ll conclude with research demonstrating that patients with CLL undergoing long-term venetoclax treatment exhibit a high incidence of cytopenias, clonal hematopoiesis, and myeloid neoplasms, and may acquire BAX mutations in normal myeloid cells.
In this week’s podcast, we’ll discuss diminished ovarian reserve in young women with sickle cell anemia, learn more about genomic alterations in adult T-cell leukemia/lymphoma, and review a novel diagnostic and prognostic index for malignancies associated with hemophagocytic lymphohistiocytosis.
In this week’s podcast, we’ll look at research demonstrating that the histone acetyltransferase HBO1 is an essential regulator of hematopoietic stem cell function during adult hematopoiesis. Next, we’ll review a large, combined analysis confirming the prognostic value of MRD assessed with next-generation sequencing in 4 randomized trials evaluating daratumumab-based therapies. We’ll conclude with research demonstrating that ferroptosis, a specific type of regulated cell death, is a key mechanism of cardiomyopathy in sickle cell disease.
In this week’s podcast, we’ll discuss the role of megakaryocytic transcription factor ARID3A in leukemia suppression, learn more about the efficacy of a third Pfizer BNT162b2 mRNA COVID-19 vaccine dose in patients with chronic lymphocytic leukemia, and discuss the association of heterozygous caseinolytic peptidase B variants with congenital neutropenia.
On this week’s podcast, we’ll review a recent analysis of phase 3 daratumumab studies looking at the prognostic impact of sustained minimal residual disease, or MRD negativity in patients with multiple myeloma. Next, we’ll hear more about a novel thrombolytic agent targeting von Willebrand factor that may represent a promising approach for the treatment of thrombotic thrombocytopenic purpura. We’ll conclude with a study demonstrating that PI3 kinase inhibitor duvelisib can be used to enhance the in vivo efficacy of CAR T cells in CLL.
In this week’s podcast, we’ll discuss real-world outcomes comparing route of CNS prophylaxis for aggressive non-Hodgkin lymphomas, learn more about the association of clonal hematopoiesis with chronic obstructive pulmonary disease, and discuss the efficacy of all-trans retinoic acid plus low-dose rituximab in corticosteroid-resistant or relapsed immune thrombocytopenia.
On today’s podcast, we’ll explore the largest case series to date describing ALK-positive histiocytosis. The authors provide new insights on the disease and its treatment with ALK inhibitors, which can provide durable responses. We’ll also review with a study that pinpoints alpha-ketoglutaric acid as consistently elevated in pediatric chronic GvHD, and finds unique metabolomic patterns that appear to distinguish different GvHD subtypes.
In this week’s podcast, we’ll talk about the long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag, learn more about anti-inflammatory and cytoprotective effects of factor VIIa, and discuss the role of IL-1 in microbiome-induced ageing of hematopoietic stem cells in mice.
In this week’s episode, we’ll review a research article that provides the first description of a targeted gene insertion approach to correct the genetic mutation underlying XMEN disease. Next, we’ll cover results of a phase 2 study that provides proof-of-principle that the JAK/STAT pathway is a promising target for the treatment of peripheral T-cell lymphomas. We’ll close with a study providing precise and up-to-date estimates on the incidence of intracranial hemorrhage in patients with hemophilia that could have important implications for preventive strategies.
In this week’s episode, we’ll review a research article demonstrating that some platelet-derived extracellular vesicles harbor proteasomes that can process and present antigens via MHC class I molecules. Next, we’ll review results of a phase 1 study of a fibril-reactive monoclonal antibody that was well tolerated and led to rapid, sustained organ responses in patients with AL amyloidosis. We’ll close with a research article suggesting that the pore-forming protein gasdermin D, which plays a crucial role in the release of neutrophil extracellular traps, is a promising drug target in sepsis.
In this week’s episode, we’ll talk about the functional properties of mesenchymal stromal cells in sickle cell disease, learn more about CAR T-cell-mediated hematotoxicity in relapsed/refractory B-cell lymphoma, and discuss dual cytokine blockade in graft-versus-host disease.
In this week’s episode, we’ll learn about a new approach for targeting Janus kinases in CRLF2-rearranged ALL, discuss risk stratification for myeloid leukemia in children with Down syndrome and learn more about how sialic acid alterations on megakaryocyte antigens regulate immune cells and platelet production.
First on today’s podcast, we’ll review results of a randomized phase 2 study demonstrating that inhibition of ROCK2 with belumosudil is well tolerated and effective in patients with steroid-refractory graft-versus-host disease. Next, we’ll review the work of researchers who have uncovered new insights into the immunopathogenesis of vaccine-induced immune thrombotic thrombocytopenia. And we’ll close with a report of a prospective longitudinal analysis that elucidates the dynamics of mutated hematopoietic stem and progenitor cells during therapy with interferon-alpha in patients with BCR-ABL1 negative myeloproliferative neoplasms.
All four studies included in this podcast present preliminary data with modest numbers of patients, and therefore, the findings should be interpreted with these limitations. Likewise, the impact of specific strains and waning antibody levels after COVID-19 vaccination will require further follow-up, since the Delta variant was not the dominant strain in circulation at the time of this research. The first two studies assess the immune responses to vaccination in two specific high-risk populations, namely, patients with lymphoma and multiple myeloma. The last two studies, one from a large European consortium and the other based on nationwide data from Israel, report on the incidence, risk factors and short-term outcomes of COVID-19 breakthrough infection in vaccinated patients with hematologic malignancies.
In this week’s episode, we’ll learn more about the efficacy of asciminib in patients with chronic myeloid leukemia who are resistant or intolerant to two or more tyrosine kinase inhibitors, discuss the role of dopamine signaling in hematopoietic stem and progenitor cell function, and learn more about elevated plasma concentration of complement factor C5 as a risk factor for venous thromboembolism.
In this week’s episode, we’ll review results of a phase 2 study showing the beneficial effects of a first-in-class factor D inhibitor as add-on therapy in PNH patients who remain anemic and are transfusion-dependent despite C5 inhibition. Next, we’ll review the work of researchers who have developed a neural network that they say is highly accurate in differentiating between bone marrow cell morphologies. We’ll close with a report demonstrating that RNA editing of antizyme inhibitor 1, or Azin1, is a novel regulator of hematopoietic cell fate that can influence self-renewal and differentiation.
In this week’s episode, we’ll learn more about the application of machine learning in molecular subclassification and prognostication of acute myeloid leukemia or AML, discuss the role of aging bone marrow in leukemia progression, and learn more about the challenges in treating bleeding disorders of unknown cause.
In this week’s episode, we’ll review a research article showing beneficial effects of prenatal immunotherapy in a mouse model of anti-CD36-mediated fetal and neonatal alloimmune thrombocytopenia. Next, we’ll look at results of a simulation analysis suggesting that gene therapy for hemophilia B is more cost-effective than on-demand or prophylactic factor treatment. We’ll conclude with a report which provides important new insights into regulation of terminal erythroid maturation at the transcriptional level that may help improve our understanding of normal and abnormal erythropoiesis.
In this week’s episode, we’ll discuss an analysis of genetic risks for CMV infection after an allogeneic hematopoietic stem cell transplant, learn more about a new multiplex gene editing approach to reactivate fetal hemoglobin in thalassemia, and discuss transcriptional rewiring of normal plasma cell development in light-chain amyloidosis and myeloma.
In this week’s episode, we’ll review results of a phase 3 randomized study demonstrating shorter time to neutrophil and platelet recovery with an ex vivo expanded hematopoietic progenitor cell product called omidubicel as compared to standard umbilical cord transplantation. Next, we’ll look at preliminary data on the development of lymphomas originating from piggyBac-modified CD19 CAR T-cells, sounding a note of caution for researchers exploring new gene modification methodologies for CAR T-cell production. We’ll conclude with a report suggesting that the vesicular protein CD63 may orchestrate the transfer of iron-rich ferritin among cells.
In this week’s episode, we will review a study that prospectively followed tuberculosis patients after treatment initiation to evaluate iron handling during the resolution of inflammatory anemia. We will also examine clinical benefit and long-term safety of gamma-retroviral gene therapy in patients with adenosine deaminase deficient severe combined immunodeficiency.
In this week’s episode, we’ll review a study providing new insights on megakaryocyte diversity and function, including a unique subpopulation that may act as immune cells. Next, we’ll review research that intriguingly reveals a putative role for the PD1 gene in cutaneous T-cell lymphoma. Lastly, we’ll conclude with a report demonstrating a lack of cross-reaction between the antibodies that cause vaccine-induced thrombocytopenia and thrombosis, and the COVID-19 spike protein.
In this week’s episode, we’ll review a study that demonstrates the efficacy of a synthetic inhibitor termed P-G6 that blocks P-selectin signaling and reduces thrombus formation in a pre-clinical model of non-occlusive venous thrombosis, learn more about how biallelic and single bZip CEBPA mutations have an equally favorable prognostic impact in acute myeloid leukemia, and examine the effects of modifying the pathophysiology of sickle cell anemia with therapeutic agents that increase oxygen affinity.
In this week’s episode, we review results of preclinical investigations that sound a note of caution regarding the potential use of JAK inhibitors as treatment for hemophagocytic lymphohistiocytosis (or HLH), research that provides new insights on how CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax, and conclude with a report that demonstrates cooperation between B cell receptor signaling and genetic lesions in CDKN2A, CDKN2B and TP53 in Richter transformation.
In this week’s episode, we will review an integrated analysis of one of the largest adult BCR-ABL1-negative B-ALL patient cohorts treated in a single trial, learn more about the genotypic and phenotypic features of patients with clonal cytopenias, and look at a study showing that a serine protease expressed in the placenta cleaves α1-antitrypsin to generate a fragment that inhibits formation of neutrophil extracellular traps in neonates.
In this week’s episode, we’ll review updated results of a phase 1b study that provide strong support for the use of fixed-duration venetoclax in patients with relapsed or refractory CLL. Next, we’ll review a research paper that provides new insights on the different subtypes of invariant natural killer T cells, which appear to have diverse immunoregulatory properties and anti-tumor effects. We will finish up with a report indicating that rare variants in the telomerase gene, TERT, are underrecognized in patients with myelodysplastic syndromes, providing a new insight into the germline genetic component of disease pathophysiology.
In this week’s episode, we will review a study that shows that BCL11B is an important oncogene in acute leukemias with myeloid and T-lymphoid features, learn more about antibody responses to SARS-CoV-2 vaccination in lymphoma patients receiving B-cell directed therapies, and examine the role of programmed death ligand 1 (or PD-L1) and the PI 3 kinase-AKT survival pathway in delayed neutrophil apoptosis at sites of tissue inflammation.
In this week's episode, we will review a study that proposes IFN-λ therapy as a novel strategy to boost gut protection in GvHD, examine the immunomodulatory effects of decitabine in ITP, and learn about the discovery of TET2 mutations in chronic natural killer large granular lymphocyte leukemia
To reach the goal of curing currently incurable hematologic malignancies, we need to go beyond focusing on single gene mutations and gain deeper understanding of the consequences of genetic alterations on gene-regulatory pathways. Edited by John Crispino, these 5 cutting-edge reviews from leaders in the their fields not only summarize our current understanding of key pathways that contribute to myeloid malignancies, but also discuss new therapeutic avenues related to them. They provide a springboard for further groundbreaking basic and clinical advances in hematologic malignancies.
In this week's episode, we will review a report on a clinical prognostic tool that identifies which group of older, fit acute myeloid leukemia patients may derive survival benefit from intensive induction and consolidation chemotherapy, learn more about how pediatric acute myeloid leukemia cells connect with mesenchymal stromal cells and the potential to exploit these cell-cell contacts in AML treatments, and examine the effects of eltrombopag and romiplostim in elderly patients with immune thrombocytopenia.
In this week's episode, we’ll discuss the safety and efficacy of brentuximab vedotin in combination with nivolumab in patients with relapsed and refractory classical Hodgkin lymphoma, learn more about the aging signature of murine hematopoietic stem cells, and discuss the role of hepatocyte neogenin in iron homeostasis.
In this week's episode, we’ll start by reviewing an intriguing study that, while not randomized, calls into question whether less-intensive induction therapies provide a survival or quality of life benefit in older patients with AML. Next, we will review the somewhat surprising findings from human and mouse model studies demonstrating that platelets downregulate T cell activity during sepsis, a finding that is associated with reduced survival. We will close with a report on a targeted genotyping approach that could reduce diagnostic and treatment delays in patients with primary CNS lymphoma.
Today’s episode is a special edition that focuses exclusively on vaccine-induced immune thrombotic thrombocytopenia, or VITT, a rare but potentially fatal syndrome associated with adenovirus-based COVID-19 vaccines. The VITT syndrome is characterized by thrombocytopenia and thrombosis in association with platelet-activating anti-platelet factor 4 antibodies. First, we’ll review an insightful Spotlight article on what is known about VITT to date. Then we’ll discuss two new brief reports in Blood that provide additional insights on VITT clinical manifestations, laboratory findings, and disease management.
In this week’s episode, we will learn more about the use of high-dose post-transplant cyclophosphamide in matched unrelated donors versus HLA haploidentical grafts, review prognostic factors and outcomes from the largest cohort of patients with angioimmunoblastic T-cell lymphoma reported to date, and look at a study that suggests that high molecular weight kininogen contributes to acetaminophen-induced liver injury.
In this week's episode, our studies include an analysis of thrombosis in pediatric patients with COVID-19, the predictive value of the CLL-international prognostic index in monoclonal B-cell lymphocytosis and Rai 0 stage CLL, and results from a phase 2 trial in newly diagnosed multiple myeloma patients treated with frontline carfilzomib, lenalidomide, and dexamethasone with autologous stem cell transplant.
In this week's episode, we will review a study that addresses the issue of reconstitution of immunity to cytomegalovirus in transplant patients receiving the antiviral drug letermovir, learn more about the role extracellular vesicles play in forming a tumor supportive stromal cell niche in follicular lymphoma, and finally, look at a report identifying a mechanism that couples the treatment of acute ischemic stroke with tissue plasminogen activator to the development of intracerebral hemorrhage.
Today’s podcast is a special edition that focuses exclusively on VEXAS syndrome, a newly identified adult-onset inflammatory syndrome with associated hematologic manifestations. VEXAS syndrome is a poor-prognosis disease caused by somatic mutations in the X-linked gene, UBA1. It was first reported by Beck and colleagues in the New England Journal of Medicine in December 2020.
In this week’s episode, we will review a study that uses a combination of mouse models to identify IL-19 as a potent cytokine capable of promoting expansion and proliferation of neutrophils, examine the effects of targeted therapies on autoimmune cytopenia in patients with chronic lymphocytic leukemia, and learn about the mechanism of excessive complement activation caused by mutations in factor H-related protein 1 in patients with atypical hemolytic uremic syndrome.
In this week’s episode, we will review the role of the hypoxia pathway in regulating neutrophil migration, explore the relationship between endothelial extracellular vesicles and the hemostatic effects of clotting Factor VIIa, and finally look at long-term outcomes with the BTK-inhibitor acalabrutinib in treatment-naive chronic lymphocytic leukemia patients.
Platelets are critical for hemostasis and thrombosis, but recent research highlights their role in many other processes, including inflammation, wound healing, and lymphangiogenesis. In this episode, Drs. José López, Elisabeth Battinelli, Craig Williams, and Owen McCarty discuss the review series on platelets and cancer. The series focuses on the emerging role of platelets in cancer, influencing tumor growth and metastasis, immune evasion, and tumor angiogenesis. The reviews present the current understanding of mutual cross talk between platelets and tumors, communication mediated by RNA transfer and extracellular vesicles, and the potential of antiplatelet agents for cancer treatment.
In this week’s episode, we will review a study demonstrating low rates of response to the Pfizer-BioNTech COVID-19 vaccine among patients with chronic lymphocytic leukemia, review a study looking at associations between post-transplantation cyclophosphamide and cytomegalovirus infection according to donor source, and look at new research indicating that abnormal venous calf muscle pump function in the legs is a risk factor for venous thromboembolism (VTE) and predictor of all-cause mortality.
In this week’s episode, we will review a study in sickle cell disease patients reporting abnormal retention of mitochondria in circulating red cells and elevated mitochondrial DNA in plasma, learn more about the fate of FLT3-ITD clones in AML patients treated with midostaurin, and look at a study showing, for the first time, that selected elderly patients with newly diagnosed multiple myeloma benefit from modification of standard myeloma treatment based on the level of frailty.
In this week’s episode we will review a phase 1 clinical trial looking at novel fully humanized BCMA-targeting CAR in patients with relapsed or refractory multiple myeloma, discuss a plenary paper reporting that different lymph nodes from patients with follicular lymphoma often have distinct clones, and finally, examine a Letter to Blood reporting high levels of markers of complement activation in plasma during quiescent phases in catastrophic antiphospholipid syndrome patients.
In this week’s episode, we will examine the prognostic significance of co-mutations in IDH-mutated AML, explore an alternative method of warfarin monitoring, and finally, consider the role of tumor suppressor TP53 in determining response to venetoclax and related agents.
In this week’s episode, we will review a randomized phase 3 study of patients with high-risk peripheral T-cell lymphoma that compares results from autologous versus allogeneic stem cell transplant during consolidation, look at a report that examines the significance of ABO-incompatible platelet transfusion on outcomes after intracerebral hemorrhage, and learn about how immune dysregulation mediated by tumor interferon signaling and myeloid-derived suppressor cells is associated with CAR-T-cell resistance in large B-cell lymphoma.
In this week’s episode, we will review a prospective study suggesting that eculizumab discontinuation based on complement genetics is a reasonable and safe strategy in patients with atypical hemolytic uremic syndrome, examine a study that provides new insights into resistance mechanisms and immune evasion in T-cell acute lymphoblastic leukemia, and finally look at a research article describing a new disorder associated with variants in the TLR8 gene that is characterized by neutropenia, infections, lymphoproliferation, B-cell defects, and bone marrow failure.
In this week’s episode, we will review a study that focuses on the morphologic alterations of stored red blood cells, learn more about how T-cell activation profiles distinguish hemophagocytic lymphohistiocytosis and early sepsis, and, finally, look at a report that describes how the WNT signaling pathway is involved in sclerodermatous chronic graft-versus-host disease and can be blocked by available therapeutics.
In this week’s episode, we consider the role of MYC and BCL2 copy number variants in double-hit diffuse large B-cell lymphoma, explore megakaryocyte-biased stem cells in JAK2-mutated myeloproliferative neoplasms, and finally, we look at long-term outcomes with emicizumab prophylaxis in patients with hemophilia, which are even better than in the first reports.
In this week’s episode, we will review a manuscript that describes a novel inherited bone marrow failure syndrome associated with defective clearance of formaldehyde by hematopoietic stem cells, learn about the first large scale analysis of the association between cancer-specific mutations in cancer cells and the incidence of cancer-specific thrombosis, and explore results from a large screening study examining the incidence and progression of monoclonal B cell lymphocytosis in families with an inherited predisposition to chronic lymphocytic leukemia.
In this week’s episode, we discuss recent studies providing new insights on the use of minimal residual disease measurements to guide treatment in patients with high-risk ALL; the increasing risk of venous thromboembolism among patients with cancer; and the use of tocilizumab in the prophylaxis of acute graft versus host disease.
In this week’s episode, we will learn more about the feasibility of combining IDH inhibitors with intensive chemotherapy in patients with newly diagnosed IDH-mutant AML, review a phenotypic and functional analysis of the inflammatory infiltrate in the Langerhans Cell Histiocytosis lesion, and discuss the results of a Phase 3 trial in patients with hemophilia A evaluating prophylactic factor replacement therapy targeting two different Factor VIII trough levels for prevention of bleeds.
In this week’s episode, we look at the role of a previously unidentified variant of DNA methyltransferase 1 as a determinant of beta-thalessemia phenotype, report on the association of vascular thromboembolism in cancer patients treated with immune checkpoint inhibitors, and finally we explore preclinical models of acute erythroid leukemia using CRISPR/Cas 9 hematopoietic genome editing.
In this week’s episode, will review a study that looks at primary diffuse large B-cell lymphoma of the central nervous system comparing tumor biologic features associated with Epstein-Barr virus, examine the functions of regulatory T cells in thrombus resolution in a mouse model, and learn more about subsequent malignant neoplasms in treated pediatric patients with Hodgkin lymphoma.
Diagnosis and treatment of acquired hemolytic anemia can be challenging. In this How I Treat series, edited by Mario Cazzola, clinical experts discuss their approaches to the treatment of patients with 4 different classes of acquired hemolytic anemia.
In this week’s episode, we will review recent studies providing new insights on frontline use of checkpoint inhibitors in classical Hodgkin lymphoma, immune escape mechanisms in diffuse large B-cell lymphoma, and the role of SRP54 mutations in congenital neutropenia.
In this week’s episode, we will review a study that provides further evidence of poor prognosis in patients with multiple myeloma who have “double hit” mutations targeting TP53, examine the early use of BCR-ABL1 kinetics to predict the likelihood of treatment free remission in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors, and learn more about a direct causative link between IL-18 with arrythmias and myocardial fibrosis in sickle cell cardiomyopathy.
In this week’s episode, we will learn more about pre-clinical work that aims to identify optimal immunotargets for treatment of pediatric AML, report on a novel path for subcutaneous administration of Factor 8, and highlight the performance characteristics of the platelet factor 4-dependent p-selectin expression assay for the diagnosis of heparin-induced thrombocytopenia.
In this week’s episode, we will learn about the cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura, review outcomes of a phase 2 trial of pomalidomide in subjects failing prior therapy of chronic graft-versus-host disease, and examine results of a phase 1/2 study looking at the use of ibrutinib and obinutuzimab plus venetoclax in patients with mantle-cell lymphoma.
In this week’s episode, we will cover recent research that provides new insights into the treatment of relapsed or refractory acute myeloid leukemia, immune-mediated thrombotic thrombocytopenic purpura, and sickle cell disease.
In this week’s episode, we will review a study that describes the pathogenic relevance of retinoic acid-responsive CD8+ T-cells in gastrointestinal graft-versus-host disease, learn more about how storage-induced disturbances of platelets is linked to changes in the number and sphingolipid content of platelet extracellular vesicles which predispose to transfusion related acute lung injury, and lastly, review the findings of a phase II study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma.
In this week’s episode, we will explore the characteristics of the tumor and immune environment as predictors of response to blinatumomab in B cell ALL, look at a new predictive tool for guiding decision-making for stem cell transplantation in acute myeloid leukemia, and review the mechanisms of how persistent terminal complement activation can still occur even in the presence of complement inhibitors targeting C3 or C5.
In this week’s episode, we will review a study that shows neutrophils are required for optimum recovery from acute lung injury in a murine model, examine the implication of germline genetic factors in the myeloproliferative neoplasm, polycythemia vera, and learn about the use of emicizumab for bleeding control in a small study of patients with acquired hemophilia A.
This week’s episode covers recent research that provides new insights in erythropoiesis, mastocytosis, and chronic active EBV. First, we’ll review a report describing how interactions between an E3 ubiquitin ligase and a heterochromatin-associated protein may serve as a “toggle” of sorts to regulate the formation of red blood cells. Next, researchers find that presence of hereditary α tryptasemia may predict the risk of severe anaphylaxis in patients with mastocytosis. Finally, we’ll review a report revealing large numbers of myeloid-derived suppressor cells in patients with EBV-associated T/NK cell lymphoproliferative disorders, which may have important implications for understanding disease pathogenesis and targeted approaches to therapy.
In this week’s episode, we will review a study that shows that non-invasive imaging of T cell metabolic activity can detect early graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, learn more about how detailed assessment of measurable residual disease in multiple myeloma can better define outcomes and how treatment resistance arises, and finally, examine the mechanism of action and pharmacokinetics of Ciraparantag, a small molecule being developed to rapidly reverse the effects of anticoagulants.
In this week’s episode, we will review a study that evaluates the role of pre-transplant leukocyte telomere length on survival outcomes in patients with myelodysplastic syndrome, learn more about a potential novel treatment for patients with WHIM syndrome, and examine a novel mechanism important for the maintenance of normal hematopoietic stem cell quiescence, and hence, long-term blood formation.
In this week’s episode, we will learn more about T-cells from SARS-CoV-2-infected individuals, review a study that describes the rapid clinical and histologic response to anti-PD1 first-line therapy in early-stage, unfavorable Hodgkin lymphoma, and discuss a meta-analysis and systematic review of outcomes of patients with hematologic malignancies and Covid-19.
In this week’s episode, we will review a study describing real-world data where PET scans following chemotherapy for primary mediastinal B-cell lymphoma were used to guide consolidative radiotherapy, learn more about the novel role of the BLOC-2 protein complex in the formation of Weibel-Palade bodies that store von Willebrand Factor in endothelial cells, and finally, examine how mutant TP53 in myelodysplastic syndrome is associated with immune checkpoint overexpression in the bone marrow.
In this week’s episode, we will review a study that describes how transfer of whole mitochondria from hematopoietic stem cells to bone marrow mesenchymal stem cells helps regenerate the stroma and its capacity to sustain hematopoietic recovery in irradiated mice undergoing stem cell transplant, examine the potential benefit of adding the BCL2-inhibitor, venetoclax, to standard treatment regimens for patients with relapsed or refractory follicular lymphoma, and finally, we will learn more about how NCOA4, the autophagic receptor for ferritin, is necessary for the mobilization of liver iron stores during stress erythropoiesis.
In this week’s episode, we will review a study that reveals a previously unknown role for the canonical Wnt signaling pathway in the regulation of granulocyte production in steady state and emergency granulopoiesis, examine the discordance in different assays that measure factor VIII activity after adenoviral-associated gene therapy, and learn about the dynamics of declining antibody levels in repeat Covid-19 convalescent plasma donors.
In this week’s episode, we will review an proof-of concept study using the bispecific antibody AFM13 in combination with a check-point inhibitor in patients with relapsed or refractory Hodgkin lymphoma, learn more about how iron restriction might be a promising new therapy for congenital erythropoietic porphyria, and review a manuscript that provides novel molecular insights into the requirement for RUNX1 in a mouse model of inversion 16 acute myeloid leukemia, providing a path forward for new therapies to treat this subgroup of AML.
In this week’s episode, we will review a study on the involvement of lysine-specific, we’ll cover some of the latest findings in COVID-19, multiple myeloma, and myelodysplastic syndromes. First, we’ll review an observational, multicenter study suggesting that convalescent plasma with anti-SARS-CoVid-2 antibodies may be a promising therapy in B-cell depleted patients who have prolonged COVID-19 symptoms. Next, we’ll discuss a research article showing that inhibition of JAK-STAT3 signaling with ruxolitinib could upregulate CD38 expression, thereby enhancing daratumumab-mediated cytotoxicity in multiple myeloma. Finally, we’ll review a report showing for the first time that in MDS, machine learning algorithms can be used to reveal novel associations between morphologic features and genetic lesions that may have important prognostic implications.
In this week’s episode, we will review a study on the involvement of lysine-specific demethylase 1A in hematopoietic stem cell expansion, examine the role of platelet receptor PAR4 in venous thromboembolism; and finally, investigate the relative contributions of maternal versus fetal hepcidin in embryonic iron endowment in both healthy and inflammatory states.
In this week’s episode, we will review a study that uncovers a role for CLCX4 in inducing the two hallmark features of primary myelofibrosis, bone marrow fibrosis and inflammation. We will next examine how genetic predisposition and altered gut microbiome can trigger the development of Precursor B-ALL in mice, and finally, learn how SARS-CoV2 spike proteins activate complement by engaging the alternative pathway, a novel finding which raises the prospect for targeted therapy of COVID-19-associated micro-angiopathy.
In this week’s episode, we will learn more about the immune defects and granule dysfunction in the leukocytes of patients with the rare recessive platelet disorder, gray platelet syndrome, review a study that examines the cost effectiveness of first-line versus third-line ibrutinib in patients with chronic lymphocytic leukemia, and review a manuscript that proposes a diagnostic classifier to facilitate the diagnosis of childhood autoimmune lymphoproliferative syndrome.
In this week’s episode, we will review a study that utilized whole-genome sequencing to define the mutational spectrum and clonal architecture of myelodysplastic/ myeloproliferative neoplasms, learn more about the association between plasma levels of growth differentiation factor 15 and the risk of venous thromboembolism, and examine the role of microenvironment myeloid cells in supporting the growth of T-cell acute lymphoblastic leukemia.
In this week’s episode, we will learn about two molecular brakes that regulate platelet activation and production, review a study showing that giving BCR-ABL1 tyrosine kinase inhibitors after allogeneic stem cell transplantation for Philadelphia-positive ALL prevents relapse, and lastly, see how investigators deciphered the role of a micro-RNA that increases platelet formation by reducing the expression of the actin-bundling protein, L-plastin, in megakaryocytes.
In this bonus episode, we welcome Blood Associate Editor, Dr. Margaret Goodell, along with colleagues Dr. Grant Challen and Dr. David Steensma as they discuss the Blood review series on mechanisms and clinical implications of clonal hematopoiesis. The articles in this series review the mechanisms driving the development of clonal hematopoiesis, the associated risks posed by clonal hematopoiesis for patients with hematologic and nonhematologic disorders and patients with inherited bone marrow syndromes, and the clinical ramifications of discovering clonal hematopoiesis and sharing the results with patients.
In this week’s episode, we will learn more about the pre-clinical and clinical development of optimized, bivalent, tandem CD20 and CD19 chimeric antigen receptor T cells for treatment of relapsed/refractory non-Hodgkin lymphoma, examine a study that reveals the first stage in the clearance of senescent red blood cells by the spleen, and review a manuscript that describes the first transgenic mouse model fully reproducing specific renal lesions and kidney dysfunction observed in human light chain deposition disease.
In this week’s episode, we will learn more about the role of hepcidin in fetal iron homeostasis, review a new study with improved outcomes in HLA-antigen mismatched transplantation, and examine how two splicing factor mutations can coexist in the same cell in patients with myeloid malignancies.
In this week’s episode, we will examine the effects of protecting and regenerating Paneth cells and intestinal stem cells in acute-graft-versus-host-disease, learn more about how Plasmodium falciparum gametocytes develop in the bone marrow by invading erythroblasts, and look at a meta-analysis of direct oral anticoagulants for treating cancer patients with acute venous thromboembolism.
In this bonus episode, we welcome Drs. Mario Cazzola, Rachel Grace, and Achille Iolascon as they discuss the Blood Review Series on Inherited Anemias. In this series, experts review the biology and pathophysiology of prominent inherited anemias and provide updated information on their management.
In this week’s episode, we start by reviewing two studies on the risks of transmitting HIV from transfusion. The first study asks whether changing the US blood donation policy for men who have sex with men from an indefinite deferral, to a deferral of 12 months from last sex, increases the risk of transfusion-transmitted HIV. The second study examines the frequency of detecting anti-HIV retroviral drugs in the serum of people attempting to donate blood. We will also review a manuscript examining the impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH chemotherapy with or without vorinostat. And lastly, we learn more about platelet hyperactivity in two recent studies of patients with COVID-19.
In this week’s episode, we will learn about vasomotor hyper-responsiveness in sickle cell disease, examine the role of neutrophil extracellular traps in the pathophysiology of immunothrombosis in COVID-19-associated acute respiratory distress syndrome, and discuss a large series evaluating allogeneic hemopoietic cell transplantation in chronic granulomatous disease.
In this week’s episode, we will review a study that identifies a new modular organization of erythropoiesis and offers a novel strategy to overcome chronic anemias, summarize a study that used data from two large phase three trials to examine the risk of thrombosis in patients with newly diagnosed multiple myeloma, and review the first report of autosomal recessive germline TET2 deficiency, which results in immunodeficiency, autoimmune lymphoproliferation, and lymphoma.
In this week’s episode we will review a study exploring recurrent somatic deletions at chromosome 13q12.2 in acute lymphoblastic leukemia leading to upregulation of FLT3, examine how matriptase-2 plays a key role in suppressing hepatic hepcidin expression, and learn about the addition of daratumumab to lenalidomide, bortezomib, and dexamethasone as a quadruple therapy for transplant eligible patients with newly diagnosed multiple myeloma.
In this week’s episode we will review a study exploring the use of demethylating agents in patients with adult T-cell leukemia-lymphoma, learn more about hematopoietic stem cell formation, and examine treatment timing and prognosis in newly diagnosed patients with acute myeloid leukemia.
In this week’s episode we will review a study exploring the use of a novel hemophilia A mouse model to examine emicizumab function in vivo, a new approach to fighting the cytokine storm of HLH with a combination of glucocorticoids and ruxolitinib, and a timely Letter to Blood about red cell-bound antibodies and transfusion requirements in hospitalized patients with COVID-19.
In this week's episode we will review a study that demonstrates how the impaired hematopoietic stem cells (HSCs) observed in β-thalassemia can be rescued by administration of parathyroid hormone, learn more about genetic variants that can increase the risk of venous thromboembolism, and explore the identification of two DNA methylation subtypes of Waldenström’s macroglobulinemia.
In this episode we will review a study identifying cyclin-dependent kinase 6 (or CDK6) as a therapeutic target of NUP98-driven acute myeloid leukemia (or AML), learn more about the largest clinical dataset on cold agglutinin disease, and examine the effects of COVID-19 on coagulation parameters as well as bleeding and thrombosis in hospitalized patients.
In this episode we’ll review the risk of bleeding after initiating treatment for acquired hemophilia A, examine the functional effect of antibodies leading to immune TTP and how this can be used as a biomarker, and finally, a blast from the past – we will discuss a study that explores the intriguing possibility that a core component driving globin gene expression became active long ago.
This week we’ll review data that suggests the pro-inflammatory environment associated with aging alters hematopoietic stem cell function by inducing IL27 receptor alpha expression, examine a study attempting to optimize antiplatelet therapy in essential thrombocythemia, and learn more about a study by investigators who have proposed that myelodysplastic syndrome patients with mutations in SF3B1 identify a new subtype of that disease.
In this bonus podcast episode Dr. Jean Soulier shares highlights of the Blood Review Series on Secondary Leukemia. In this review series, experts provide new insights into the pathobiology of secondary acute myeloid leukemias arising in diverse genetic or acquired, benign or malignant hematologic disorders.
This week we will explore the impact of calreticulin (or CALR) haploinsufficiency on hematopoietic stem cell activity in the context of myeloproliferative neoplasms, explore mechanisms of leukemogenesis related to the E2A-PBX1 fusion protein in childhood B-cell acute lymphoblastic leukemia, and learn about the connection between intestinal microbiota, their metabolite short chain fatty acids and chronic graft versus host disease after allogeneic stem cell transplantation.
In this week’s episode we’ll examine the cause and clinical significance of dysplastic hematopoiesis at time of diagnosis in patients with multiple myeloma, review a multi‐omics analysis of patients that have undergone blastic transformation of chronic myeloid leukemia, and learn about HLA alleles that are either risk factors or protective for immune-mediated TTP in Japan.
In this week’s episode we’ll review a study focusing on the causes and impact of the inflammation of aging on hematopoietic stem cell function, learn about the potential influence of the endothelial cell protein C receptor in the pathogenesis of hemophilic arthropathy, and assess a novel function of GPS2 on erythropoiesis.
In this week’s episode we’ll review results of a trial of venetoclax plus low-dose cytarabine in untreated patients with acute myeloid leukemia who are ineligible for intensive chemotherapy, learn how HRI-regulated transcription factor ATF4 activates BCL11A transcription to silence fetal hemoglobin expression, and assess new data demonstrating that aromatase is a novel neosubstrate of cereblon responsible for thrombocytopenia caused by immunomodulatory drugs.
This week’s episode will discuss the impact of sickle cell disease on the bone marrow vascular niche, highlight more about the evolution of retrovirus-infected premalignant T-cell clones in adult T-cell leukemia/lymphoma, and assess the outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome.
In this week’s episode we will review a report on the use of hydroxyurea as an alternative to transfusion therapy for the prevention of recurrent strokes in patients with sickle cell anemia, learn more about why some erythroblasts continue to produce hemoglobin F in adults, and review a study that explores cancer outcomes in patients with short telomere syndromes.
Today we’ll review data on the high frequency of germline RUNX1 mutations in patients with acute myeloid leukemia, learn more about the development of an international prognostic score that predicts time to first treatment in CLL patients with early, asymptomatic disease, and explore the possibility of improving the activity of virus-directed immunotherapies against certain types of EBV tumors.
In this week’s episode we’ll learn why anticoagulation may play a role in the prevention of vaso-occlusive events in sickle cell disease, review data that could help predict the risk of VTE and bleeding in hospitalized patients, and find out if Ruxolitinib is a viable treatment of steroid-refractory acute graft-versus-host disease.
This week’s episode will review a report on a new mouse model with an enhanced ability to support human hematopoietic and tumor engraftment, explore more about increased mTOR activation in idiopathic multicentric Castleman disease, and assess the feasibility and efficacy of CD19-targeted CAR-T cells with concurrent ibrutinib for CLL.
This week’s episode will review the incidence and fate of clonal hematopoiesis among donors and recipients of related allogeneic hematopoietic stem cell transplantation, examine the manifestations and clinical course of patients with a particular subtype of Fanconi anemia, and assess three clinical studies that demonstrate high rates of efficacy and low rates of toxicity of daratumumab in patients with previously treated AL amyloidosis.
This week’s episode will highlight the development of a factor VIII replacement therapy for patients with severe Hemophilia A, examine a novel pathway of resistance of FLT3-ITD+ AML cells to FLIT3 inhibitors, and review long-term results of a pilot study in children with low risk B-cell ALL conducted in a limited-resource setting.
In this bonus podcast episode, Drs. Nancy Berliner and Laurie Sehn lead a discussion on this series of authoritative reviews on a collection of rare systemic hematologic disorders that are frequently difficult to recognize, diagnose, and treat. The series highlights new genomic and proteomic insights that inform our understanding of their pathophysiology and treatment.
This week’s episode will review evidence that selecting donors with specific types of natural killer cells leads to improved outcome in stem cell transplantation, review an analysis of platelet transfusion in cerebral hemorrhage, and explore the challenges of diagnosing recurrent ipsilateral deep vein thrombosis.
This week’s episode will examine data on the impact of the FDG uptake level on predicting subsequent high-grade histological transformation in follicular lymphoma, explore clonal tracking in gene therapy patients as a method for understanding human hematopoiesis, and review a study on the recognition of platelet factor 4-von Willebrand factor complexes by heparin-induced thrombocytopenia antibodies as a basis for the pathogenesis of HIT.
In this week’s episode we’ll learn about novel insights into the link between innate immune responses and activation of coagulation during gram-negative sepsis, examine the impact of GPRASP proteins on hematopoietic stem cell transplantation, and explore the dynamics of clonal hematopoiesis in anemia of older individuals.
This week’s episode will review data on spliceosomal gene mutations, evaluate the impact of Ruxolitinib on weight gain, and assess the effect of compliment blockade with eculizumab on high risk patients with stem cell transplant associated thrombotic microangiopathy.
This week’s episode will review the clinical correlates of NT5C2 mutations in relapsed ALL, the impact of Crovalimab, a recycling monoclonal antibody against complement component C5 in paroxysmal nocturnal hemoglobinuria, and the relationship between leukocyte NADPH oxidase and leukotriene B4 and neutrophilic inflammation in the context of chronic granulomatous disease
This week’s episode will review a novel treatment for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis, learn more about the behavior of leukemic clones in patients with acute myeloid leukemia receiving venetoclax-based combination therapies, and review the role of the integrin alpha9beta1 in arterial thrombosis.
This week's episode will explore interventions that may improve outcomes in sepsis by stabilizing neutrophil extracellular traps, or NETs, discuss the use of a novel strategy to generate CAR T cells that react with surface antigens on AML cells, and review data about how chronic lymphocytic leukemia cells become resistant to Venetoclax.
In this episode Dr. Catherine Bollard, Blood Associate Editor provides highlights of this commissioned review series Understanding and Treating Primary Immunodeficiency, that highlights cutting-edge developments in the biology and management of primary immune deficiencies.
This week's episode will review efforts to improve the activity of CAR T cells, explore the impact of Protein C activator AB002 on thrombus development, and look at results from a UK study on minimal residual disease status and outcome after transplantation in NPM1-mutated AML.
This week’s episode will examine how graft versus host disease in the colon is driven by an inflammatory cytokine produced by specialized donor T cells, review a prospective, multicenter study to assess the frequency and clinical relevance of low level mutations in chronic myeloid leukemia, and learn about a potential new therapeutic that blocks the activity of the iron-regulatory hormone Erythroferrone to reduce iron overload in thalassemia.
This week’s episode will review treatment for secondary prevention of venous thromboembolism in children, a therapeutic strategy for relapsed or refractory B-cell acute lymphoblastic leukemia, Ivosidenib monotherapy in patients with newly diagnosed AML with mutations in the isocitrate dehydrogenase 1 gene, and survival outcomes of chronic Lymphocytic Leukemia patients treated with Ibrutinib.
This week’s episode will examine the critical role of platelet necrosis in ischemic stroke injury, the discovery of the molecular basis for the PEL blood group, and the impact of NPM1/FLT3-ITD genotypes in patients with acute myeloid leukemia.
In this episode we welcome Drs. Thomas Ortel, Jeffrey Weitz, and Kenneth Bauer as they discuss the Blood Review Series on the Treatment of Venous Thrombotic Disorders. In this review series, experts contribute 6 seminal reviews that focus on the treatment of venous thromboembolism (VTE) in adults and children, the management of VTE developing in unusual locations and in the setting of thrombophilia, and new targets and antithrombotic therapies in development.
In this episode we’ll examine a new strategy to improve the durability of remission after CAR T-cell therapy for pediatric B cell leukemia, explore the genomic landscape of Breast Implant-Associated Anaplastic Large Cell Lymphomas, and discuss a new report showing that the occurrence of arterial thrombotic events following the diagnosis of myeloproliferative neoplasms is associated with a significantly increased risk of a second cancer.
Today we’ll examine the role of heredity vs. environmental factors in the evolution of age-related clonal hematopoiesis, review the first systematic approach to uncover all possible activating point mutations within and around the transmembrane domain of the thrombopoietin receptor in myeloproliferative neoplasms, and discuss the role of complement activation and mutations in complement regulatory genes in patients with thrombotic or catastrophic antiphospholipid syndromes.
In this episode we highlight the development of intensified T-cell acute lymphoblastic leukemia-focused protocols, the use of a thrombopoietin agonist for thrombocytopenia following allogeneic hematopoieticstem cell transplantation, and a crucial step forward in the development of miRNA therapies targeting myeloid diseases.
This episode will explore the consequences of a loss of the interaction between mutant calreticulin and another ER resident protein, and how this may promote myeloproliferative neoplasms, the role of a calcium-induced transcription factor in driving diffuse large B-cell lymphoma signaling, and a comparison of two therapies for standard risk acute graft-versus-host disease.
This episode will highlight a unique treatment for refractory hematologic malignancies, therapy-induced mutations impacting the genomic landscape of relapsed acute lymphoblastic leukemia, and a unique approach to avoiding chronic graft-versus-host disease.
This episode highlights articles and commentaries that help expand our understanding of prognostic biomarkers in CLL, learn more about a streamlined analysis of the granulocyte transcriptome in myeloproliferative neoplasms, explore the role of neutrophil extra cellulartraps in adenosine deaminase deficiency, and examine the function of the plant homeodomain-like finger protein 6, in hematopoietic stem cell self-renewal.
The topics in this episode include studies on the mechanism of progression in myelodysplastic syndromes, the value of gait speed as a predictor of outcomes in older adults with hematologic malignancies, the role of extended eltrombobag therapy on severe aplastic anemia, and the role of the Hedghog pathway mutations in chronic lymphocytic leukemia.
This episode discusses the immune engine in classical Hodgkin Lymphoma, osteopontin’s keyrole in the chemoattraction of neutrophils in transfusion-related acute lunginjury,B-1 progenitor acute lymphoid leukemia, and exciting new ideas for heparin-induced thrombocytopenia treatment.
This episode explores four compelling topics which include: Hemophagocytic Lymphohistiocytosis, a severe and potentially fatal systemic inflammatory syndrome, CAR T-cell therapy in follicular lymphomas, Sickle Cell Anemia and sickle trait in thrombosis, and mutated calreticulin in myeloproliferative disorders.
The article highlighted in this trailer "The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells" was published June 6, 2019; Blood, Volume 133, Issue 23.
The authors of this article are: Satoru Miyagi , Patrycja Sroczynska , Yuko Kato , Yaeko Nakajima-Takagi , Motohiko Oshima , Ola Rizq , Naoya Takayama , Atsunori Saraya , Seiya Mizuno , Fumihiro Sugiyama , Satoru Takahashi , Yumi Matsuzaki , Jesper Christensen , Kristian Helin , Atsushi Iwama.