Optimal timing of allogeneic hematopoietic stem cell transplant in MDS

Myelodysplastic neoplasms (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, dysplasia, and a significant risk of progression to acute myeloid leukemia. Allogeneic hematopoietic stem cell transplant (HSCT) remains the only potentially curative therapy for MDS, particularly for higher-risk disease, but its success depends heavily on the timing of the procedure. This review explores the evolving evidence and decision models guiding the optimal timing of HSCT, balancing the risks of disease progression and transplant-related morbidity and mortality. Key considerations include advancements in disease-specific and transplant-specific risk stratification, such as the IPSS-M and transplant-specific scoring systems, which integrate clinical, cytogenetic, and molecular data to personalize timing decisions. Improvements in haploidentical HSCT and supportive care have expanded the feasibility and safety of HSCT for diverse patient populations, including the elderly. Prospective trials underscore the survival benefits of HSCT over non-transplant approaches for higher-risk MDS, while ongoing studies aim to address uncertainties in pretreatment, post-transplant maintenance therapy, and donor selection. By synthesizing these developments, this review provides practical insights into optimizing HSCT timing to improve outcomes for MDS patients.