SOHO State of the Art Updates and Next Questions | Best of Stem Cell Transplant: Recent Advances in Allogeneic Hematopoietic Cell Transplantation.

Allogeneic hematopoietic cell transplantation is undergoing rapid transformation, propelled by a wave of practice-changing studies that are reshaping how donors are selected, how graft-versus-host disease (GVHD) is prevented, and how post-transplant relapse is managed. Here we review the major advances of the past several years, focusing on practice-changing studies from 2024 to 2026, and the questions they raise. The adoption of post-transplant cyclophosphamide (PTCy) as a near-universal GVHD prophylaxis backbone has diminished the long-standing primacy of human leukocyte antigen matching, enabling comparable outcomes with mismatched unrelated (MMUD) and haploidentical donors and expanding access for patients of non-European ancestry; contemporary guidelines now endorse concurrent donor searches and prioritization of younger donors. Building on the BMT CTN 1703 trial, PTCy-based prophylaxis has become a standard across conditioning intensities and donor types, while correlative studies illuminate both its mechanism and its trade-offs. Complementary strategies, including frontline and prophylactic ruxolitinib, adoptive regulatory T-cell (Treg) therapy, and the precision-engineered Orca-T graft, are broadening the prophylaxis repertoire and beginning to separate GVHD control from the loss of immune competence and graft-versus-leukemia activity. For FLT3-ITD AML, the MORPHO trial and subsequent analyses have established measurable residual disease-directed gilteritinib maintenance, advancing a molecularly individualized approach to relapse prevention. Together, these developments mark a decisive shift from a uniform transplant paradigm toward biomarker-guided, precision-based care, and they define the priorities for the next generation of clinical trials.