Blood Podcast

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.

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.Review Series on Mechanisms of Hematologic Malignancies

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

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.Review Series on Platelets and Cancer

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.