Blood Podcast

Germline predisposition variants occur in all age groups in MDS, αβ-haplo-HCT excels in children with acute leukemias/MDS, and poor outcomes after CAR T cell failure in B-cell lymphomas

In this week’s episode, research shows that in patients with myelodysplastic syndromes, or MDS, the frequency of pathogenic or likely pathogenic germline variants is relatively high across all age groups, not just younger patients. Based on these results, it may be time to expand genetic testing to all patients. Next, we'll review primary results of a prospective, multicenter study of children with acute leukemias or MDS who underwent T-cell receptor αβ+ and CD19+ cell-depleted haploidentical HC...

Predicting VTE in multiple myeloma, azithromycin promotes relapse after HSCT, and dual antigen targeted NK cells in B cell malignancies

In this week’s episode we’ll discuss the newly developed PRISM score for risk prediction of venous thromboembolism in multiple myeloma, learn more about relapse-promoting effects of azithromycin after allogeneic stem cell transplantation, and discuss the efficacy of off-the-shelf natural killer cells in preventing antigen escape in lymphoma and leukemia.

Using MRD to guide CLL treatment intensity, donor NK cells boost immune reconstitution after haplo-BMT, and EZH2 drives retinoic acid resistance in variant APL

In this week’s episode we discuss encouraging results of a phase 2 study using a sequential ibrutinib-venetoclax treatment approach driven by MRD findings in individual patients with chronic lymphocytic leukemia, or CLL. Next, we examine new research demonstrating that donor natural killer cells trigger release of beta-2 microglobulin by host dendritic cells, greatly accelerating donor-derived immune reconstitution after allogeneic bone marrow transplant in mice. We’ll look at the therapeutic im...

Tolerability of CD19 CAR T cells in lymphoma, causes of platelet spherocytosis, and using prebiotics to reduce GVHD

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.

Transplant in adult Ph+ ALL, acalabrutinib and ventricular arrythmias, and antibody prevention of fetal/neonatal alloimmune thrombocytopenia

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. ...

Restricting dietary methionine in AML, transferrin in high altitude-induced hypercoagulability, and LIF as protection against GVHD

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.

Sickle hemoglobin activates monocytes via TLR4, germinal center B cells provide a niche for T-cell lymphoma, and a combination immunosuppression regimen for acquired hemophilia A

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...

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.

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. Blood Review Series on Megakaryopoiesis...

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.

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 demonstrating that b...

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, we’ll review ...

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 review a paper ...

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 model of acute ...

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 blood group...

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 with sickle cel...

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 review results of ...

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.