Hematology — Weekly Evidence Brief

Recent studies highlight that post-transplant cyclophosphamide (PTCy) is revolutionizing hematopoietic cell transplantation (HCT) by safely expanding the donor pool. PTCy mitigates the historical risks associated with isolated HLA-DQB1 mismatch, 7/8 mismatch, and older donor age in unrelated donor HCT, showing no significant detriment to overall or progression-free survival 1. Similarly, for 8/10 HLA-mismatched unrelated donors, PTCy improved overall survival and reduced the risk of acute graft-versus-host disease (GVHD) 2. In acute lymphoblastic leukemia (ALL) patients undergoing HCT with PTCy, a CMV-negative donor for a CMV-negative recipient improved leukemia-free and overall survival, though older donor age still increased acute GVHD risk 3. Additionally, UM171-expanded cord blood transplantation demonstrates equivalent or improved outcomes compared to conventional donor sources, including significantly lower chronic GVHD rates and better survival outcomes than many other graft types 4.

Significant advancements are emerging for acute myeloid leukemia (AML), particularly in unfit patients and those with relapsed disease. For newly diagnosed unfit AML, venetoclax-hypomethylating agents (Ven-HMA) are the current standard-of-care, with response and survival rates critically influenced by tumor genetics; favorable predictors include NPM1MUT and IDH2MUT, while TP53MUT and FLT3-ITD are unfavorable 5. For FLT3 wild-type AML patients relapsing after allo-HSCT, a challenging population with poor prognosis, salvage therapy including sorafenib was associated with a significantly higher composite complete remission rate (65.8%) and improved 2-year overall survival (47.4%) compared to non-sorafenib treatment, without increasing GVHD 6. Furthermore, novel proteomic subtypes and a prognostic aging score are refining AML risk stratification beyond current genetic markers, offering more personalized treatment insights 7.

Precise risk stratification and novel transplantation approaches are improving outcomes in pediatric hematologic malignancies. In childhood acute lymphoblastic leukemia (ALL) post-HCT, pre-HSCT minimal residual disease (MRD) positivity is associated with significantly worse event-free survival and higher relapse rates, emphasizing the importance of MRD negativity. MRD positivity at day 100 post-HSCT is a particularly strong prognostic factor for relapse 8. For T-cell ALL patients, haploidentical HCT combined with umbilical cord blood (haplo-cord HCT) demonstrated better 2-year overall and disease-free survival compared to haploidentical HCT alone, with improved immune reconstitution 9. In pediatric normal karyotype AML (NK-AML), the prognosis is independently affected by NPM1 and FLT3-ITD status, with mutated NPM1 associated with favorable outcomes and FLT3-ITD with inferior outcomes 10.

Personalized medicine continues to advance, with new approaches for refractory conditions and refined prognostic tools. Daratumumab, a CD38-targeting monoclonal antibody, showed promising rapid and sustained responses in a pediatric patient with severe, refractory immune-mediated cytopenias post-allogeneic HSCT, suggesting a potential novel therapy for these difficult cases 11. In multiple myeloma, a novel T-cell-based 'immune age' metric has been developed, which more accurately predicts clinical outcomes in older patients receiving daratumumab-based therapy than traditional calendar age, even after adjusting for frailty, potentially guiding immunotherapy decisions 12. The ongoing development of CAR T-cell therapies for AML is also being streamlined by international consensus guidelines, aiming to standardize trial design and reporting to accelerate best practices and improve patient outcomes 13.