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.
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In this Review Series episode, Associate Editor Dr. Hervé Dombret speaks with Dr. Mark Litzow about the latest immunotherapy advances for Acute Lymphoblastic Leukemia (ALL). The discussion highlights innovative treatments like blinatumomab and inotuzumab, which are showing remarkable success in clinical trials, including an 85% three-year survival rate and over 90% complete remission in elderly patients. Researchers are focusing on reducing chemotherapy intensity, developing personalized treatment approaches, and identifying optimal immunotherapy strategies for different ALL subtypes. The conversation underscores a promising shift towards more targeted, less toxic treatments that could significantly improve patient outcomes across various age groups and disease characteristics. These emerging therapies represent a potential paradigm shift in ALL treatment, offering hope for more effective and less aggressive therapeutic interventions.
Read Dr. Litzow's paper “Incorporation of immunotherapy into frontline treatment for adults with B-cell precursor acute lymphoblastic leukemia” or find the whole review series on acute lymphoblastic leukemia in volume 145 issue 14 of Blood Journal.
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.
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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.
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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.
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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.
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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.
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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.
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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).
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.
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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.
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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.
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In this week's episode we’ll learn more about the use of ruxolitinib plus dexamethasone to treat newly diagnosed patients with adult hemophagocytic lymphohistiocytosis; lysine-specific demethylase-1 inhibitors as a potential new class of therapies for sickle cell disease and other beta-globinopathies; and insights into clinical characteristics of patients with von Willebrand factor levels that are lower than normal but higher than those typically used to diagnose von Willebrand disease.
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In this episode, Associate Editor Dr. Philippe Armand discusses the Review Series on mantle cell lymphoma with author Dr. Christine Ryan. Both were authors of "Frontline management of mantle cell lymphoma", and discuss shifts in treatments and new research.
In this week's episode, we'll learn about rapid, high-sensitivity diagnostic assays for TTP, or thrombotic thrombocytopenic purpura, that can reduce unnecessary treatments. After that: enhancing PD-1 blockade in relapsed/refractory extranodal NK/T-cell lymphoma. In a single-arm, phase 2 study, combined CD38 and PD-1 inhibition demonstrated durable responses and manageable safety. Finally, a lymphoma horror story with a happy ending. CREBBP mutations create a zombie enzyme that competes with its wild-type counterparts. By enforcing CD40 signaling, a bispecific antibody overcomes this effect and induces lymphoma cell death.
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In this week's episode we’ll learn more about a novel mouse model that recapitulates many of the properties of human sickle cell SC disease; results from the induction phase of the risk-adapted MIDAS trial of isatuximab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed, transplant-eligible multiple myeloma; and a link between splicing factor mutations and competitive fitness in myelodysplastic syndrome stem cells.
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In this week's episode, we'll learn about using AI to assess transplant risk in myelofibrosis. In a step toward personalized medicine, researchers report on a machine learning model that identifies 25% of patients with poor outcomes. After that: preventing priapism in men with sickle cell anemia. A recent phase 2 feasibility study shows high rates of recruitment, retention, and adherence to oral therapies, coupled with a significant reduction in the risk of this difficult complication. Finally, new research indicates that hallmarks of terminal T-cell exhaustion are absent in multiple myeloma, from diagnosis through maintenance therapy. We explore these provocative and counterintuitive findings arising from profiling of blood and marrow samples.
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In this week's episode, we’ll learn more about social determinants of health that impact access to allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia, or AML; use of megakaryocyte growth factor receptor-based stem cell depletion as part of pretransplant conditioning in ex vivo autologous gene therapy; and identification of an eight-protein risk signature as well as a novel single protein biomarker, soluble oncostatin M receptor, for risk stratification in AML.
Featured Articles:
Blood editor Dr. Laurie Sehn discusses the topic of "Aggressive non-Hodgkin lymphoma: defining and managing high-risk subsets" featuring Drs. Mark Roschewski, Grzegorz Nowakowski, and Neha Mehta-Shah, who each contributed to the articles featured in the review series on high-risk aggressive lymphoma.
See the full review series on high risk lymphoma in volume 144, issue 25 of Blood.
