Navigating post-transplant relapse in acute myeloid leukemia: donor lymphocyte infusion, emerging cellular immunotherapies, and clinical management

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the major obstacle to curing acute myeloid leukemia (AML). Even with modern advances, it continues to be the leading cause of treatment failure. The biology behind post-transplant relapse is multifaceted: leukemic cells evolve ways to evade immune detection, donor immune cells can become dysfunctional, the bone marrow microenvironment shifts in ways that favor leukemia, and the transplant itself reshapes immune dynamics in complex ways. This review brings these pieces together by combining mechanistic understanding with practical, evidence-based treatment pathways. The goal is to offer a clear framework for both preventing relapse and managing it when it occurs. We also highlight emerging strategies—such as biomarker-guided interventions, more precise immune modulation, microbiome-based approaches, and the integration of patient-reported outcomes—that aim to improve long-term disease control and overall survivorship. Current tools for risk assessment and immune monitoring are summarized, including measurable residual disease (MRD), donor chimerism, TIM-3 + leukemic stem cell tracking, leukemia-associated antigen-specific T-cell responses, and microbiome profiling. Together, these approaches help clinicians better anticipate relapse, tailor interventions, and refine post-transplant care.