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

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.

Featured Articles:

• Ruxolitinib combined with dexamethasone for adult patients with newly diagnosed hemophagocytic lymphohistiocytosis in China
• Novel, potent, and orally bioavailable LSD1 inhibitors induce fetal hemoglobin synthesis in a sickle cell disease mouse model
• Clinical phenotype and pathophysiological mechanisms underlying qualitative low VWF

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.

Find the full review series in Volume 145 Issue 7 of Blood: "Review series on mantle cell lymphoma: sands shifting in the darkness"

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.

Featured Articles:

• Rapid ADAMTS13 activity assays for thrombotic thrombocytopenic purpura: a systematic review and meta-analysis
• Efficacy of combined CD38 and PD-1 inhibition with isatuximab and cemiplimab for relapsed/refractory NK/T-cell lymphoma
• Blunted CD40-responsive enhancer activation in CREBBP-mutant lymphomas can be restored by enforced CD4 T-cell engagement

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.

Featured articles:

• A novel mouse model of hemoglobin SC disease reveals mechanisms underlying beneficial effects of hydroxyurea
• Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial
• Cell-autonomous dysregulation of interferon signaling drives clonal expansion of SRSF2-mutant MDS stem/progenitor cells

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.

Featured Articles:

• Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis
• A controlled trial for preventing priapism in sickle cell anemia: hydroxyurea plus placebo vs hydroxyurea plus tadalafil
• Hallmarks of T-cell exhaustion and antigen experience are absent in multiple myeloma from diagnosis to maintenance therapy

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:

• Social Determinants of Health and Access to Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia
• cMPL-Based Purification and Depletion of Human Hematopoietic Stem Cells: Implications for Pretransplant Conditioning
• Blood-Based Proteomic Profiling Identifies OSMR as a Novel Biomarker of AML Outcomes

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.

In this week's episode, we' ll learn about how TET3 has a key role in GVHD. In mice, a deficiency of Tet3 in donor T cells inhibited pathogenic immunoglobulin class switching and suppressed lung fibrosis. Accordingly, TET3 may be a new therapeutic target in chronic GVHD. After that: rilzabrutinib, a BTK inhibitor for ITP. In a randomized, placebo-controlled trial, treatment produced rapid and durable platelet responses, with acceptable safety, in adults with immune thrombocytopenia who had failed multiple previous therapies. Finally: exploring pre-TCR surface expression patterns in T-cell ALL. Co-inhibition of the interleukin-7 receptor and pre-T cell receptor pathways may play a therapeutic role for a subset of T-lymphoblastic leukemias.

Featured Articles: 

• Deficiency of T follicular helper cell Tet3 DNA demethylation inhibits pathogenic IgG2c class switching and chronic GVHD
• Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study
• Surface pTα expression predicts LCK activation and preclinical synergy of LCK and JAK coinhibition in adult T-ALL