Blood Podcast

In this week's episode we'll learn how cytomegalovirus infection early in life depletes preleukemic cells in a mouse model of B-cell acute lymphoblastic leukemia. After that we'll discuss new research, where GVHD targets organoid-forming bile duct stem cells in a TGF-beta-dependent manner. Conversely, a TGF-beta inhibitor protects these stem cells against GVHD and mitigates biliary dysfunction. Finally, we'll hear about the seven-year outcomes for venetoclax-ibrutinib in relapsed or refractory mantle cell lymphoma. In addition to long-term survival benefits, researchers report durable treatment-free remissions and effective retreatment in patients with MRD-negative complete responses.

Featured Articles: 

• Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic
  leukemia
• GVHD targets organoid-forming bile duct stem cells in a TGF-β–dependent manner
• Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and
  treatment-free remissions

In this week's episode we'll learn about iron, HFE hemochromatosis, and infections. In this large, population-based study, both high and low levels of plasma iron and transferrin saturation were associated with increased risks of infection. Then, we'll discuss how bispecific antibodies improve CAR T-cell response in B-cell malignancies. In-vitro and in-vivo data demonstrate enhanced therapeutic efficacy when a CD20-directed bispecific antibody is given in combination with CD19-directed CAR-T cells. Finally, we'll hear about determinants of outcome in NPM1-mutated AML. In a large series of patients with NPM1-mutated AML, investigators identified several variables beyond FLT3-ITD that adversely impacted outcomes.

Featured Articles:

• Iron, hemochromatosis genotypes, and risk of infections: a cohort study of 142 188 general population individuals
• Molecular, clinical, and therapeutic determinants of outcome in NPM1-mutated AML
• CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models

In this week's episode we’ll discuss how immune fitness impacts response to teclistamab in relapsed/refractory multiple myeloma; learn more about a new mechanism of resistance to asciminib conferred by the BCR::ABL1 M244V mutation, and discuss the impact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease.

Featured Articles:

• Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in MajesTEC-1
• BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib
• Impact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease

In this week's episode we’ll discuss the safety and efficacy of decitabine in older patients with AML; learn how heme-induced loss of renovascular endothelial protein C receptor promotes chronic kidney disease in sickle mice, and discuss the outcomes of treatment with HLA-mismatched HSCT with TCRab/CD19 lymphocyte depletion or post-HSCT cyclophosphamide for inborn errors of immunity.

Featured Articles:

• Decitabine in older patients with AML: Quality of life results of the EORTC-GIMEMA-GMDS-SG randomized phase III trial 
• Heme induced loss of renovascular endothelial protein C receptor promotes chronic kidney disease in sickle mice 
• Outcomes of HLA-mismatched HSCT with TCRab/CD19 depletion or post-HSCT cyclophosphamide for inborn errors or immunity 

In this week's episode we'll discuss minimal residual disease as an intermediate clinical endpoint for multiple myeloma. Then, we'll learn about IPSS-R downstaging before transplant in MDS. Finally we'll hear about the connection between hereditary angioedema and venous thromboembolism. 

Featured Articles:

• EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma 
• Does IPSS-R down-staging before transplantation improve the prognosis of patients with Myelodysplastic Neoplasms? 
• Increased risk of venous thromboembolism [or VTE] in young and middle-aged individuals with hereditary angioedema: a family study

In this week's episode we’ll discuss the safety and efficacy of acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL; learn more about alternative donor transplantation for severe aplastic anemia and discuss clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation.

Featured Articles: 

• Acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL: Final efficacy and ctDNA analysis of the CLL2-BAAG trial 
• Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT 
• Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation 

In this week's episode we'll learn about the clinical benefit of complete remission with partial hematological recovery, or CRh, in patients with Acute Myeloid Leukemia (AML) treated with molecularly targeted drugs. Then we'll hear about a large cohort of patients with PNH were studied to detail PNH-related thrombotic events, unravel determinants of thrombosis, and evaluate anti-coagulation strategies. Finally, we'll see how new research shows that SOX11 expression is restricted to EBV-negative Burkitt lymphoma, and is associated with a specific genetic landscape. 

Featured Articles:

• Complete Remission with Partial Hematological Recovery as a Palliative Endpoint for Treatment of Acute Myeloid Leukemia 
• Paroxysmal nocturnal hemoglobinuria-related thrombosis in the era of novel therapies: a 2043 patient/years analysis 
• SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features 

In this week's episode we’ll discuss the mutational and transcriptional landscape of pediatric BCP lymphoblastic leukemia; learn more about the role of platelet-derived TGF-β1 in immune thrombocytopenia; and discuss the findings from a phase 3 trial of mavorixafor in WHIM syndrome.

Featured Articles:

• Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma 
• Platelet-derived TGF-β1 induces functional reprogramming of myeloid-derived suppressor cells in immune thrombocytopenia 
• Phase 3 randomized trial of mavorixafor, CXCR4 antagonist, in WHIM syndrome 

In this week's episode we'll discuss new insights on the role of GM-CSF in establishing immune memory. The authors propose that the coordination of opposing immune memory programs, driven by GM-CSF, may be essential to efficient, yet controlled, innate immune responses. After that: Interleukin-1 inhibition in TTP. Researchers explore the potential of recombinant IL-1 receptor antagonist, anakinra, in a murine model of thrombotic thrombocytopenic purpura—an uncommon but potentially fatal disorder with limited therapeutic options. Finally, we'll learn about CAR T-cell therapy outcomes by race and ethnicity in large B-cell lymphoma. Non-Hispanic Black patients had lower rates of response and progression-free survival in axi-cel clinical trials and real-world data, raising awareness and giving further insights into potential inequitable access to care.

Featured Articles:

• GM-CSF receptor expression determines opposing innate memory phenotypes at different stages of myelopoiesis 
• Mortality, cardiac and cerebral damage reduction by IL-1 inhibition in a murine model of TTP 
• Real-World and Clinical Trial Outcomes in Large B-cell Lymphoma with Axicabtagene Ciloleucel Across Race and Ethnicity 

Introduced by Associate Editor Robert Zeiser, this Review Series focuses on the problem of immune escape by acute myeloid leukemia (AML). The series opens with a review of how AML escapes T-cell–driven elimination and then focuses on how p53 function impinges on AML recognition by immune cells. The series finishes with a summary of new approaches to tackling this major problem.

Featured Series:

• Introduction to a review series on oncogenic signaling and immune evasion in hematologic malignancies