Blood Podcast

In this week's episode, we’ll learn more about relationships between Epstein-Barr virus genomic variants and human diseases, including hematological malignancies; the presence and timing of somatic GATA1 mutations and their relationship to a Down syndrome-specific form of leukemia; and new definitions for high-risk multiple myeloma that emphasize the presence of two or more high-risk cytogenetic abnormalities.Featured Articles:Association of Epstein-Barr virus genomic alterations with human pathologiesClinical significance of preleukemic somatic GATA1 mutations in children with Down syndromeBiallelic antigen escape is a mechanism of resistance to anti-CD38 antibodies in multiple myeloma

Dr. Mark Litzow, a leading hematology professor from the Mayo Clinic, discusses groundbreaking immunotherapy advancements for Acute Lymphoblastic Leukemia (ALL). He highlights the impressive clinical trial results of treatments like blinatumomab and inotuzumab, boasting high remission rates and improved survival, especially among older patients. The conversation emphasizes the shift towards personalized, less toxic therapies, aiming to enhance patient outcomes and reduce chemotherapy intensity. This innovative approach could revolutionize ALL treatment, offering renewed hope for many.

In this week's episode we'll learn about Azacitidine in VEXAS syndrome. Treatment can provide responses in patients with this complex autoinflammatory disorder. But relapse rates were high, so long-term therapy may be required to maintain disease control. After that: A step forward in precision blood matching. High-throughput array genotyping enables extended matching to reduce antibody formation. The results show the potential for reducing harm in regularly transfused patients. Finally, identifying a new vulnerability in TP53-mutated AML. Loss of the tumor suppressor BAP1 defines a unique subtype of TP53-mutated de novo AML. BAP1 loss also confers sensitivity to BCL-xL inhibitors in vivo, opening a new therapeutic avenue.Featured ArticlesEfficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from FRENVEXArray genotyping of transfusion-relevant blood cell antigens in 6946 ancestrally diverse study participantsLoss of BAP1 defines a unique subtype of TP53-mutated de novo AML and confers sensitivity to BCL-xL inhibitors

Discover the lasting impacts of diffuse large B-cell lymphoma on immune profiles, revealing how treatment can leave patients with a dysfunctional immune system. Explore new insights into plasminogen activation and its surprising lack of role in preventing venous thromboembolism. Additionally, delve into the exciting potential of PARP inhibitors in targeting hematological malignancies with epigenetic mutations. This engaging discussion sheds light on significant advancements in understanding and treating blood cancers.

Discover how mutations in TET2 influence myeloid malignancies and the role of NCOA4 in supporting Tet2-deficient cells. Dive into the promising results from a groundbreaking CAR T therapy that could offer hope for patients with T-cell leukemia and lymphoma. Lastly, explore new insights from a comprehensive study on classical Hodgkin lymphoma genetics through circulating tumor DNA, revealing key subtypes and prognostic markers. These topics promise to reshape our understanding of blood cancers.

In this week's episode we'll learn about targeting NPM1 in acute myeloid leukemia. Researchers report the first clinical evidence of a menin inhibitor inducing complete remissions in AML with a NPM1 mutation. This validates NPM1 as a new therapeutic target in AML, alongside FLT3, IDH1/2, and KMT2A. Also on the podcast: targeting CD137 to prevent graft-versus-host disease. In nonhuman primates, a single dose of a CD137 antibody-drug conjugate provided long-term protection, with one important caveat: the potential for viral reactivation.Featured Articles: Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 studyA single dose of a CD137 antibody–drug conjugate protects rhesus macaque allogeneic HCT recipients against acute GVHD

Blood Editor, Dr. Thomas Coates interviews Dr. Emanuele Angelucci on his paper, "How I manage iron overload in the hematopoietic cell transplantation setting" which is featured in Blood's "How I Treat Series on Iron Overload in Hematologic Disorders". See the full How I Treat series in volume 145 issue 4 of Blood. 

In this week's episode we'll learn about how by combining PET response with circulating tumor DNA, or  ctDNA, in newly treated patients with follicular lymphoma, investigators identify those patients likely to progress within 24 months of initial treatment, also known as POD24. After that: Immune hotspots in aplastic anemia. These newly identified hotspots potentially represent sites in the bone marrow where the active immune response takes place, driving the destruction of hematopoietic stem and progenitor cells. Finally, allogeneic transplantation for Hodgkin lymphoma in the checkpoint inhibitor era. In a large, retrospective study, patients with prior checkpoint inhibitor exposure had remarkable outcomes, particularly when post-transplant cyclophosphamide was used.Featured Articles: Combined PET and ctDNA response as predictors of POD24 for follicular lymphoma after first-line induction treatmentImaging Mass Cytometry Reveals the Order of Events in the Pathogenesis of Immune-Mediated Aplastic AnemiaOutcomes of Allogeneic HCT in Hodgkin Lymphoma in the Era of Checkpoint Inhibitors: A Joint CIBMTR and EBMT Analysis

Explore the impact of exogenous CD19 stimulation on CAR T-cell persistence in treating B-cell acute lymphoblastic leukemia. Discover innovative rapid immune assays that enhance the diagnosis of heparin-induced thrombocytopenia, making recognition quicker and more reliable. Delve into new survival prediction models for chronic myelomonocytic leukemia, which integrate clinical data and genetic factors to refine patient selection for stem cell transplants, ultimately improving outcomes.

Join Dr. Selina Luger and a panel of AML experts: Dr. Andrew Wei, a researcher on azacitidine and venetoclax at the Peter MacCallum Cancer Centre; Dr. Gail Roboz, who specializes in maintenance therapy at Weill Cornell Medicine; Dr. Eunice Wang, who addresses secondary AML challenges at Roswell Park; and Dr. Courtney DiNardo, focused on targeted therapies at MD Anderson. They discuss groundbreaking outpatient therapies, the complexities of maintenance strategies, and advancements in differentiating agents that may improve patient outcomes.