Blood Podcast

In this week's episode we'll learn about persistent changes in immune profiles in patients who have had diffuse large B-cell lymphoma, or DLBCL, and other cancers; that plasminogen activation and plasmin activity do not appear to play a role in routine physiological prevention of venous thromboembolism, or VTE; and about a novel mechanism that makes hematological malignancies carrying epigenetic mutations susceptible to PARP inhibitors.

Featured Articles:

• Large B-cell lymphoma imprints a dysfunctional immune phenotype that persists years after treatment
• Plasminogen activation and plasmin activity are not required to prevent venous thrombosis/thromboembolism
• Transposable elements as novel therapeutic targets for PARPi-induced synthetic lethality in PcG-mutated blood cancer

In this week's episode, we'll learn about how TET2 is often mutated in myeloid malignancies and clonal hematopoiesis. In new work, expansion of Tet2-mutant HSPCs was dependent on Ncoa4, the cargo receptor mediating ferritinophagy. We’ll iron out the implications. After that: a double-oh-seven license to kill in T-cell leukemia/lymphoma. WU-CART-007 is an off-the-shelf CAR T product with manageable safety and encouraging efficacy. With further work, it could become a new option for patients in urgent need of therapy. Finally: a comprehensive genetic study of classical Hodgkin lymphoma using circulating tumor DNA. This new research provides novel and complex insights on genetic subtypes, prognostic biomarkers, neoantigens in the disease environment, and more.

Featured Articles:

• An in vivo barcoded CRISPR-Cas9 screen identifies Ncoa4-mediated ferritinophagy as a dependence in Tet2-deficient hematopoiesis
• Phase 1/2 trial of anti-CD7 allogeneic WU-CART-007 for patients with relapsed/refractory T-cell malignancies
• A comprehensive genetic study of classic Hodgkin lymphoma using circulating tumor DNA

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 study
• A 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 treatment
• Imaging Mass Cytometry Reveals the Order of Events in the Pathogenesis of Immune-Mediated Aplastic Anemia
• Outcomes of Allogeneic HCT in Hodgkin Lymphoma in the Era of Checkpoint Inhibitors: A Joint CIBMTR and EBMT Analysis

In this week's episode, we’ll learn more about how exogenous CD19 stimulation affects CAR T-cell persistence in B-cell acute lymphoblastic leukemia treated with CD19 CAR T-cell therapy; new algorithms that incorporate sequential rapid immune-assays, intended to improve diagnosis of heparin-induced thrombocytopenia, and resource-adaptive survival prediction models to help guide management of patients with chronic myelomonocytic leukemia.

Featured Articles:

• Outcomes of PLAT-02 and PLAT-03: evaluating CD19 CAR T-cell therapy and CD19-expressing T-APC support in pediatric B-ALL
• Sequential combinations of rapid immunoassays for prompt recognition of heparin-induced thrombocytopenia
• BLAST: a globally applicable and molecularly versatile survival model for chronic myelomonocytic leukemia

In this episode, Associate Blood editor Dr. Selina Luger leads a discussion with Drs. Courtney DiNardo, Eunice Wang, Andrew Wei and Gail Roboz about the advances in treatment options for Acute Myeloid Leukemia (AML). The conversation highlights new combinations like Venetoclax-azacitidine, challenges with differentiation syndrome, and emerging strategies for secondary AML patients. The authors emphasize moving beyond traditional one-size-fits-all treatments to more nuanced, patient-specific care that considers individual genetic profiles and potential complications. These insights provide a comprehensive overview of the latest innovations in AML treatment, offering healthcare professionals critical updates on managing this complex disease.

See the full How I Treat series on Acute Myeloid Leukemia in volume 145 issue 12 of Blood journal.

In this week's episode, we’ll learn more about the effects of daratumumab maintenance on minimal residual disease in patients with newly diagnosed, transplant-eligible multiple myeloma; the role of neutrophils in the pathophysiology of myeloproliferative neoplasms; and a genome-wide association study that identified novel genetic loci associated with the risk of heavy menstrual bleeding.

Featured Articles

• Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results
• Defective neutrophil clearance in JAK2^V617F myeloproliferative neoplasms drives myelofibrosis via immune checkpoint CD24
• Genome-wide meta-analysis of heavy menstrual bleeding reveals 36 risk loci

In this week's episode we'll learn more about enhanced transplant characteristics; targeting the JAK-STAT pathway with ruxolitinib in patients with adult-onset Still’s disease and macrophage activation syndrome; and a pair of trials demonstrating lack of benefit for the anti-CD47 monoclonal antibody magrolimab in newly diagnosed acute myeloid leukemia.

Featured Articles

• Heterogeneity of high-potency multilineage hematopoietic stem cells and identification of “Super” transplantability
• Ruxolitinib targets JAK-STAT signaling to modulate neutrophil activation in refractory macrophage activation syndrome
• Magrolimab plus azacitidine vs physician’s choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study
• The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy

In this week's episode, we'll learn about a JAK inhibitor to prevent complications of CD19-directed CAR T-cell therapy. In a phase 2 study, itacitinib was well tolerated and demonstrated promising reductions in the incidence of cytokine release syndrome and neurotoxicity. After that: investigators report direct interactions between ChAdOx1 and platelets under arterial shear conditions. Investigators say it’s a novel biophysical mechanism that potentially contributes to post-vaccination arterial thrombosis. Finally, we explore lineage switch, an emerging form of acute leukemia relapse with dismal outcomes. It arises rapidly following antigen-targeted immunotherapy, highlighting the importance of advanced methods for detection and treatment.

Featured Articles: 

• Itacitinib for the prevention of IEC therapy–associated CRS: results from the 2-part phase 2 INCB 39110-211 study
• Shear-dependent platelet aggregation by ChAdOx1 nCoV-19 vaccine: a novel biophysical mechanism for arterial thrombosis
• Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia