Alle afleveringen
403 afleveringen, van nieuw naar oud
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Improved risk assessment in adult BCR-ABL1-negative B-ALL, value of clone metrics in clonal cytopenias, a placental protease generates a peptide to inhibit NET formation
16 september 2021 · 18 min
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. Lees meer
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Fixed-duration venetoclax in relapsed CLL, differing effects of invariant NK T cells, and under recognition of rare TERT variants in MDS
9 september 2021 · 23 min
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. Lees meer
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Activated BCL11B in acute leukemias, SARS-CoV-2 antibody responses in lymphoma patients receiving B-cell therapies, and PD-L1 in neutrophil apoptosis and tissue inflammation
2 september 2021 · 18 min
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. Lees meer
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Review Series on Mechanisms of Hematologic Malignancies
26 augustus 2021 · 28 min
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. Lees meer
Review Series on Mechanisms of Hematologic Malignancies
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IFN-λ therapy for GvHD, mechanism of decitabine in ITP, and TET2 mutations in chronic NK-LGL leukemia
26 augustus 2021 · 18 min
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 Lees meer
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Choosing chemotherapy for older patients with AML, the role of the microenvironment in pediatric ALL, and efficacy of thrombopoietin receptor agonists in elderly patients with ITP
19 augustus 2021 · 18 min
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. Lees meer
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Brentuximab plus nivolumab in refractory/relapsed Hodgkin lymphoma, the signature of aging hematopoietic stem cells, and hepatocyte neogenin in iron homeostasis
12 augustus 2021 · 16 min
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. Lees meer
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Latest Research on the Intensity of AML Therapy in Older Patients, Platelets and T cell Activity in Sepsis, and Genotyping for CNS Lymphoma
5 augustus 2021 · 19 min
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. Lees meer
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Vaccine-induced Immune Thrombotic Thrombocytopenia
29 juli 2021 · 18 min
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. Lees meer
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Latest research in post-transplant cyclophosphamide in matched unrelated versus haploidentical donors, outcomes in patients with AITL, and high molecular weight kininogen in acetaminophen-induced liver injury
22 juli 2021 · 17 min
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. Lees meer
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Latest research in thrombosis in pediatric COVID-19, prognostic tool for very early stage CLL, and frontline treatment for newly diagnosed myeloma
15 juli 2021 · 18 min
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. Lees meer
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Latest Research: Immunity to CMV, lymphoma microenvironment, and tPA induced bleeding
8 juli 2021 · 15 min
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. Lees meer
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VEXAS: A Newly Identified Adult-onset Hemato-inflammatory Syndrome
1 juli 2021 · 17 min
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. Lees meer
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Season 2, Episode 25
24 juni 2021 · 19 min
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. Lees meer
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Season 2, Episode 24
17 juni 2021 · 22 min
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. Lees meer
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Review Series on Platelets and Cancer
10 juni 2021 · 35 min
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. Lees meer
Review Series on Platelets and Cancer
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Season 2, Episode 23
10 juni 2021 · 20 min
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. Lees meer
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Season 2, Episode 22
3 juni 2021 · 18 min
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. Lees meer
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Season 2, Episode 21
27 mei 2021 · 17 min
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. Lees meer
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Season 2, Episode 20
20 mei 2021 · 20 min
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. Lees meer
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Season 2, Episode 19
13 mei 2021 · 19 min
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. Lees meer
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Season 2, Episode 18
6 mei 2021 · 20 min
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. Lees meer
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Season 2, Episode 17
29 april 2021 · 19 min
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. Lees meer
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Season 2, Episode 16
22 april 2021 · 20 min
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. Lees meer
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Season 2, Episode 15
15 april 2021 · 18 min
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. Lees meer
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Season 2, Episode 14
8 april 2021 · 19 min
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. Lees meer
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Season 2, Episode 13
1 april 2021 · 18 min
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. Lees meer
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Season 2, Episode 12
25 maart 2021 · 20 min
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. Lees meer
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Season 2, Episode 11
18 maart 2021 · 19 min
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. Lees meer
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Season 2, Bonus: How I Treat Series: Acquired Hemolytic Anemia
15 maart 2021 · 20 min
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. Lees meer
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Season 2, Episode 10
11 maart 2021 · 17 min
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. Lees meer
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Season 2, Episode 9
4 maart 2021 · 16 min
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. Lees meer
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Season 2, Episode 8
25 februari 2021 · 19 min
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. Lees meer
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Season 2, Episode 7
18 februari 2021 · 17 min
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. Lees meer
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Season 2, Episode 6
11 februari 2021 · 17 min
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.
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Season 2, Episode 5
4 februari 2021 · 18 min
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. Lees meer
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Season 2, Episode 4
28 januari 2021 · 20 min
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. Lees meer
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Season 2, Episode 3
21 januari 2021 · 14 min
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. Lees meer
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Season 2, Episode 2
14 januari 2021 · 18 min
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. Lees meer
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Season 2, Episode 1
7 januari 2021 · 17 min
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. Lees meer
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Season 1, Episode 52
24 december 2020 · 17 min
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. Lees meer
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Season 1, Episode 51
17 december 2020 · 17 min
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. Lees meer
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Season 1, Episode 50
10 december 2020 · 17 min
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. Lees meer
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Season 1, Episode 49
3 december 2020 · 16 min
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. Lees meer
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Season 1, Episode 48
26 november 2020 · 17 min
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. Lees meer
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Season 1, Episode 47
19 november 2020 · 18 min
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. Lees meer
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Season 1, Episode 46
12 november 2020 · 18 min
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. Lees meer
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Season 1, Episode 45
5 november 2020 · 19 min
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. Lees meer
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Season 1, Episode 44
29 oktober 2020 · 20 min
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. Lees meer
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Season 1, Episode 43
22 oktober 2020 · 20 min
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. Lees meer