Blood Podcast

Lineage switching in MLL/AF4 leukemia, ibrutinib in mantle cell lymphoma with CNS relapse, and gilteritinib plus azacitidine in newly diagnosed FLT3-mutated AML

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.

Lenalidomide and subsequent TP53-mutated myeloid neoplasms, abnormal uterine bleeding after VTE, and novel tri-specific antibody for B-ALL

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.

Blood Review Series on Megakaryopoiesis and Platelet Production

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.

Prognostic impact of NPM1 and FLT3 mutations in AML, progression of monoclonal B cell lymphocytosis, and creating RBCs with rare blood types in the laboratory

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.

Transplant outcomes in adults with immunodeficiencies and erythroblastic islands as niches for terminal erythropoiesis and granulopoiesis

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.

Ticagrelor in pediatric sickle cell disease, UBA1 translation impacts severity of VEXAS syndrome, and T-cell immunity and chemotherapy response in ALL

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.

Race affects treatment outcomes in iTTP, 2022 ELN AML recommendations, and a comprehensive MRD assessment in MCL

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 demonstr...

The International Consensus Classification: An interview with Drs. Daniel Arber and Elias Campo

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.

Tranexamic acid prophylaxis in heme malignancies, N-glycosylation as a therapeutic vulnerability in CALR-mutant MPN, and myocardial fibrosis in sickle cell anemia

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.

Rest alleviates T-cell exhaustion by bispecific antibodies, exercise vs desmopressin in mild hemophilia A, and targeting MDM2 to enhance antileukemia immunity after transplant

Sutimlimab vs placebo in cold agglutinin disease, the impact of etoposide versus auto-transplant in PTCL, and the role of pulmonary NETs in sickle cell disease

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, w...

Rivaroxaban after cancer surgery, genetics and survival in severe aplastic anemia, and a 5-year follow up of rituximab-venetoclax in relapsed/refractory CLL

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.

Stroke in hereditary TTP, and germline DDX41 variants as risk factors and prognostic markers in myeloid neoplasms

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.

Cost effectiveness of first-line daratumumab in MM, base-edited CAR T cells for T-ALL, and the role of SETBP1 mutations in chronic neutrophilic leukemia

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 rev...

Immune thrombocytopenia and adenoviral SARS-COV2 vaccines, genomics, and a risk assessment model of anti-CD19 CAR T-cell treatment outcomes in lymphoma

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.

Naturally selected CD7 CAR T cell therapy for T-lineage malignancies, CD4+ T cell exhaustion and PD-L1 inhibition in B-ALL, and tPA-induced phosphorylation of occludin in stroke

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 mod...

Role of PIEZO1 in leukocyte extravasation, CD8+ T-cell activation in macrophage activation syndrome, and ABO O blood group as a novel risk factor for HIT

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...

Long-term ibrutinib-rituximab vs FCR in CLL, procoagulant platelet sentinels in prevention of inflammatory bleeding, and new SERPINC1 variants in thrombophilia

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.

Malignancy risk from genetically modified immune effector cells, p53 immunohistochemistry as a new tool in AML, and phenotypic escape from CD19-directed immunotherapies.

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.

Overcoming CAR T cell resistance in myeloma, why anti-CCR4 antibody therapy in CTCL sometimes fails, and corticosteroids increase risk of VOE in sickle disease

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 wit...

Salvage therapy with NICE for Hodgkin lymphoma, BMP2/SMAD pathway activation in leukemic transformation, and the role of zinc in T-cell reconstitution after HSCT

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.

MRD and post-transplant outcomes in older AML patients, enhancer hijacking in a novel high-risk B-other ALL subtype, and ruxolitinib in pediatric HLH 

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 revie...

Anti-PF4 antibodies after Covid vaccination, CAR T-cell therapy for CNS leukemia, and advances in Diamond-Blackfan anemia

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.

Fixed-duration ibrutinib + venetoclax for CLL, aryl hydrocarbon receptor in idiopathic pneumonia syndrome, and VWF propeptide and multimerization

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 ...

HEATR3 variants as a new cause of Diamond-Blackfan anemia, zanubrutinib in mantle cell lymphoma, and HMGB1 inhibits Epo signaling in anemia of inflammation

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.

HLA-DQ heterodimers and transplantation, the genomic landscape of LGL leukemia, and an updated classification of hemochromatosis

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 o...

Role of macrophage NOX2 in alveolar homeostasis, hydroxyurea versus peginterferon alfa-2a in high-risk PV and ET, and the emerging PV treatment landscape

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 cu...

Microbiome and CD4 T-cell recovery after allogeneic HCT, and a paradigm shift to CAR T-cells in the second line for large B-cell lymphoma?

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.

Canakinumab in SCA, antigen-specific donor T-cells to prevent post-transplant relapse in ALL, and nasopharyngeal mucosal immunity defects in transplanted SCID patients

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.

Timing (and utility) of CNS prophylaxis in DLBCL, Apollo deficiency in a bone marrow failure syndrome, and GATA1 mutants in congenital anemia

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 f...

Obinutuzumab plus lenalidomide in advanced follicular lymphoma, mechanisms of anemia in children with malaria, and granulocyte microvesicles for septic shock

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.

Structural racism and AML survival, promoter competition and hemoglobin switching, and CAR T-cell therapy and high-risk cytogenetics in ALL

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-ce...

Targeting the PBX1-FOXM1 axis in myeloma, SF3B1 mutations in MDS, and pulmonary artery hypertension-associated mortality in β-thalassemia patients

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.

Novel high-risk subtypes in adult B-ALL, Liso-cel CAR-T therapy in CLL, and liquid biopsies in large B-cell lymphomas

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 aggressiv...

Effective treatments for kaposiform hemangioendothelioma, causes of vascular dysfunction in sickle cell patients, and better strategies to select therapy in older adults with AML

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.

COVID-19 vaccination in patients with blood cancers and recalibrating the HLA barrier in haploidentical stem cell transplantation  

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. 

Cell therapy options for chemo-sensitive DLBCL, PIGA mutations in a novel subtype of hemochromatosis, and triplet combination therapy in high-risk CLL 

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.

Germline predisposition mutations in AML, a new way to resolve NETs, and venetoclax and BAX mutations in normal myeloid cells of CLL patients

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...

Ovarian reserve in sickle cell anemia, genomic landscape of adult T-cell leukemia/lymphoma, and a new prognostic index for HLH-associated heme malignancies 

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.

Role of HBO1 in HSC function, robust MRD analysis in multiple myeloma, and cardiac ferroptosis in sickle cell disease

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 k...

The ARID3A transcription factor suppresses leukemia, a COVID-19 booster shot benefits CLL patients, and advances in the genetics of congenital neutropenia

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.

Sustained MRD negativity & outcomes in myeloma, therapeutic targeting of VWF in TTP, and improving CAR T-cells in CLL with PI3 kinase inhibition

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...

Does route of CNS prophylaxis for DLBCL matter?, the connection between CHIP and COPD, and ATRA plus low-dose rituximab in ITP

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.

A spectrum of ALK-positive histiocytosis, and metabolites as biomarkers for GvHD diagnosis and risk assignment

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.

Long-term outcomes in severe aplastic anemia, cytoprotective effects of factor VIIa, and the role of IL-1 in hematopoietic stem cell ageing

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.

CRISPR cure for XMEN disease?, JAK inhibition in T-cell lymphomas, and intracranial hemorrhage in hemophilia

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 ...

Antigen presentation by platelet extracellular vesicles, fibril-reactive monoclonal antibody therapy for AL amyloidosis, and targeting gasdermin D in sepsis

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 ...

Mesenchymal stromal cells in SCD, CAR T-cell-mediated hematotoxicity in B-cell lymphoma, and dual cytokine blockade in GVHD

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.

PROTACs for JAKs in CRLF2-rearranged ALL, risk stratification in Down syndrome-associated leukemia, and how losing sialic acid activates immune cells in ITP

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.

Belumosudil for chronic GVHD, mechanistic insights into VITT, and factors driving molecular response in IFNα-treated MPNs

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 m...