In this week's episode, we'll hear about new insights into PU.1-mutated agammaglobulinemia. Researchers show that haploinsufficiency of the master transcriptional regulator PU.1 causes agammaglobulinemia and dendritic cell deficiencies. These patients experience an array of infectious and non-infectious complications, but not leukemia. After that: venetoclax-based induction therapy in younger patients with AML. Venetoclax plus decitabine was associated with superior safety and non-inferior response rates compared to intensive chemotherapy. Is it time to consider lower-intensity therapy beyond older and unfit patients? Finally, a focus on venous thromboembolism. Researchers link BGAT, an enzyme pivotal to determining blood type, to risk of future VTE. They say high plasma levels of BGAT contribute to risk above and beyond what can be explained by von Willebrand factor and Factor VIII.

Featured Articles:

• One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them
• Venetoclax and decitabine vs intensive chemotherapy as induction for young patients with newly diagnosed AML
• Histo–blood group ABO system transferase plasma levels and risk of future venous thromboembolism: the HUNT study

In part two of the How I Treat Series on Transfusion Medicine Dr. Erica Wood interviews the "How I Manage Major Hemorrhage" author group: Drs. Jeannie Callium, Keyvan Karkouti, and Ron George.

Find the full published review series in Volume 145 Issue 20 of Blood Journal.

In this week's episode we’ll learn about how frequent blood donation affects clonal hematopoiesis in older, male blood donors; the effect of immune microenvironment on response to bispecific antibodies in diffuse large B-cell lymphoma; and the feasibility of adding blinatumomab to early consolidation therapy in CD19-positive Ph-negative B-cell acute lymphoblastic lymphoma.

Featured Articles

• Clonal Hematopoiesis Landscape in Frequent Blood Donors
• Integrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody response
• Upfront Blinatumomab Improves MRD Clearance and Outcome in Adult Ph-negative B-lineage ALL: The GIMEMA LAL2317 Phase 2 Study

In this two-part series, Dr. Erica Wood talks with Drs. Masja de Haas, Helen Savoia, and Stella Chou about their articles in the How I Treat Series on Transfusion Medicine. Topics include noninvasive prenatal testing for red blood cell and platelet antigens, transfusion cases in sickle cell disease, and pregnant patients who are alloimmunized to RBC antigens.

Find the full published review series in Volume 145 Issue 20 of Blood Journal.

In this week's episode, we'll learn about stopping myeloma maintenance therapy in the modern era. New research suggests that many patients in remission can discontinue lenalidomide, remaining treatment-free, without jeopardizing disease response. After that: a novel congenital neutropenia syndrome. Mutations in the COPZ1 gene impact myeloid differentiation and development of neutropenia. Researchers describe the mechanisms and propose a treatment strategy for restoring granulopoiesis. Finally, ruxolitinib maintenance therapy after allogeneic transplant. In a phase 2 study, this treatment strategy was associated with low rates of chronic graft-versus-host disease. Investigators say the use of JAK inhibitors in this context warrants further study.

Featured Articles: 

• Sustained bone marrow and imaging MRD negativity for 3 years drives discontinuation of maintenance post-ASCT in myeloma
• A new severe congenital neutropenia syndrome associated with autosomal recessive COPZ1 mutations
• Low rates of chronic graft-versus-host disease with ruxolitinib maintenance following allogeneic HCT
  
  

In this week's episode, we’ll learn more about how measurable residual disease might help guide decisions about post-transplant gilteritinib maintenance in FLT3-ITD acute myeloid leukemia, or AML; how stemness contributes to chemotherapy resistance in AML; and effects of babesiosis on red blood cells from individuals with sickle cell disease, sickle cell trait, and wild-type hemoglobin. 

Featured Articles:

• Measurable residual disease and post-transplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML 
• GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia 
• Babesiosis and Sickle Red Blood Cells: Loss of Deformability, Heightened Osmotic fragility and Hyper-vesiculation 

In this week's episode, we'll hear about how researchers look toward the lung, and find uniquely programmed blood stem cells. This study is the first to fully characterize hematopoietic stem and progenitor cells in the adult human lung. After that: researchers develop a neural network-based probabilistic classifier, DLBclass, that assigns all diffuse large B-cell lymphomas into one of five genetic subtypes. It’s an inclusive taxonomy that they say provides actionable genetic information in almost all patients with DLBCL. Finally, new insights on NETS, or neutrophil extracellular traps. In the liver vasculature, NET removal leads to secondary inflammation, resulting in new waves of NETS that may impact future infection. We’ll review these and other findings from this recent mouse model study.

Featured Articles:

• Decoding functional hematopoietic progenitor cells in the adult human lung
• DLBclass: a probabilistic molecular classifier to guide clinical investigation and practice in diffuse large B-cell lymphoma
• Donor regulatory T-cell therapy to prevent graft-versus-host disease

In this week's episode we’ll learn more about how phosphoseryl-tRNA kinase inhibition promotes cell death in acute myeloid leukemia, or AML; APOE gene variants and their association with post-hematopoietic stem cell transplant outcomes in AML; and pathways by which chronic inflammation and oxidative stress may lead to cardiomyopathy in patients with sickle cell disease.

Featured Articles:

• PSTK inhibition activates cGAS-STING, precipitating ferroptotic cell death in leukemic stem cells 
• Common Hereditary Variants of the APOE Gene and Posttransplant Outcome in Acute Myeloid Leukemia 
• 17R-Resolvin D1 Protects Against Sickle Cell Related Inflammatory Cardiomyopathy in Humanized Mice 

In this How I Treat series episode Blood Associate Editor, Dr. Jason Gotlib speaks with Drs. Aaron Gerds, Andreas Reiter, and Claire Harrison. The conversation focuses on the work and contributions of these authors to How I Treat Myeloproliferative Neoplasms, and exciting advances in the treatment and management of MPNs.

See the full How I Treat series in volume 145 issue 16 of Blood.

In this week's episode we'll learn about the role of autologous transplant for relapsed myeloma. In an updated analysis of the GMMG ReLApsE trial, salvage autologous transplant offered no survival benefit compared to control chemotherapy. These findings may have clinical implications in an era of alternative, and highly effective, treatment options. After that: Response to DDAVP, or desmopressin, in bleeding disorders. This study is the first large scale meta-analysis to assess the response rate to DDAVP in bleeding disorders. Authors provide new insights into determinants of response, which vary according to the disease type. Finally, turning to diffuse large B cell lymphoma. Germinal center B cells depend on the activity of DOT1 and EZH2 to maintain their pro-proliferative identity. New research shows that combined treatment with DOT1L and EZH2 inhibitors has synergistic activity in vitro.

Featured Articles:

• Salvage autologous transplant in relapsed multiple myeloma: long-term follow-up of the phase 3 GMMG ReLApsE trial
• DDAVP response and its determinants in bleeding disorders: a systematic review and meta-analysis
• Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of diffuse large B-cell lymphoma