Blood Podcast

In this week's episode we’ll learn more about the ASCEND study, which investigated first-line asciminib in chronic phase chronic myeloid leukemia; a new risk score for myeloid neoplasm transformation in patients with clonal cytopenia of undetermined significance; and use of RHD genotyped D-positive blood transfusions in patients with sickle cell and unexpected anti-D antibodies.

Featured Articles

• Asciminib Monotherapy as Frontline Treatment of Chronic Phase Chronic Myeloid Leukaemia - Results from the ASCEND Study
• Risk Prediction for Clonal Cytopenia: Multicenter Real-World Evidence 
• Genotyped RhD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D 

In this week's episode we'll learn about the updated phase 3 results on fixed-dose venetoclax plus obinutuzumab in previously untreated CLL. Then, we'll hear about dual epi-immunotherapy in classical Hodgkin lymphoma. Finally we'll explore redefining risk of treatment failure in CML.

Featured Articles:

• Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study
• Epigenetic agents plus anti-PD-1 reprogram the tumor microenvironment and restore antitumor efficacy in Hodgkin lymphoma
• A predictive model for therapy failure in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy

In this week's episode we’ll learn more about the role of ERG loss-of-function variants in bone marrow failure and hematological malignancies, a proposed pathway linking factor 11 activation to increased vascular permeability during inflammation, and new clinical criteria for diagnosing anemia, defining transfusion-dependence, and evaluating anemia treatment responses in patients with myelofibrosis.

Featured Articles:

• Germ line ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition
• Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo
• Proposals for revised International Working Group–European LeukemiaNet criteria for anemia response in myelofibrosis

In this week's episode, we'll learn about the role of a platelet-specific glycoprotein receptor in abdominal aortic aneurysm formation, the influence of TP53 mutations on outcomes for patients with 5q-deleted myelodysplastic syndrome, and a rational combination treatment intended to produce more durable responses in patients with refractory B-cell acute lymphoblastic leukemia who are treated with CAR T-cell therapy.

Featured Articles:

• Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic target
• Influence of TP53 gene mutations and their allelic status in myelodysplastic syndromes with isolated 5q deletion
• A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia

In this week's episode we'll learn about refining risk stratification in T-cell acute lymphoblastic leukemia, or ALL. After that, we'll discuss a novel gene therapy approach in severe alpha-thalassemia. Investigators describe an innovative mouse model and an effective gene therapy approach, renewing prospects for the development of novel strategies to treat this disease. Finally, we'll hear about how genomic profiling has helped identify subgroups associated with distinct clinical phenotypes and outcomes in the molecular taxonomy of myelodysplastic syndromes, or MDS.

Featured Articles 

• NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of
  patients
• Use of HSC-targeted LNP to generate a mouse model of lethal α-thalassemia and treatment via lentiviral
  gene therapy
• Molecular taxonomy of myelodysplastic syndromes and its clinical implications

In this week's episode we’ll discuss a novel tripartite fusion drives treatment resistance in acute promyelocytic leukemia. In some patients with atypical APL, these novel retinoic acid receptor gene fusions result in truncation of the ligand binding domain of the retinoic acid receptor protein, resulting in non-responsiveness to treatment with all-trans retinoic acid. After that: managing immune thrombotic thrombocytopenia or iTTP without therapeutic plasma exchange, or TPE. Finally, hope for motherhood after allogeneic HCT.

Featured Articles: 

• Critical role of tripartite fusion and LBD truncation in certain RARA- and all RARG-related atypical APL
• Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange
• Hope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation (a national multicenter study)

In this week's episode we’ll discuss the safety and efficacy of pirtobrutinib with or without rituximab in relapsed/refractory CLL; learn more about erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine; and discuss how targeting PKC alpha alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin.

Featured Articles:

• Fixed-duration pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL: Phase 1b BRUIN trial
• Murine models of erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine
• Targeting PKCα alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin

In this week's episode we'll discuss outcomes following hematopoietic stem cell transplantation in pediatric patients with Fanconi anemia. Then, we'll learn about how new research shows that the transcription factor Foxo1, commonly associated with glucose metabolism, regulates hepcidin expression and systemic iron homeostasis. Finally, in Latin America: using clinical networks to improve outcomes in patients with acute promyelocytic leukemia. After clinical networks were established, survival and relapse rates improved substantially, highlighting the effectiveness of this unique intervention strategy in low- and middle-income countries.

Featured Articles: 

• Outcomes of hematopoietic stem cell transplantation in 813 pediatric patients with Fanconi anemia
• Foxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasis
• Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic
  leukemia

In this week's episode we’ll discuss how CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemia; learn more about the effect of ATM germline pathogenic variants on the outcomes in children with ataxia-telangiectasia and hematological malignancies; and discuss the preclinical efficacy of a potent, selective menin-KMT2A inhibitor JNJ-75276617 in KMT2A- and NPM1-altered leukemias.

Featured Articles:

• CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemia
• ATM germ line pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematological
  malignancies
• Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in
  KMT2A- and NPM1-altered leukemias

In this week's episode we'll discuss HA-1-targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation. Next, we'll learn about how 4D intravital imaging in mice reveals the key role of platelets as a source of procoagulant membranes in hemostasis. Finally, we'll hear about modifications to a common induction and maintenance treatment for treatment-naïve mantle-cell lymphoma.

Featured Articles

• HA-1–targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell
  transplantation
• 4D intravital imaging studies identify platelets as the predominant cellular procoagulant surface in a mouse
  hemostasis model
• Randomized study of induction with bendamustine-rituximab ± bortezomib and maintenance with
  rituximab ± lenalidomide for MCL