Allogeneic hematopoietic stem cell transplantation in adult with acute lymphoblastic leukemia: evolving indications and modalities in shifting landscape

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been a cornerstone in the treatment of adult acute lymphoblastic leukemia (ALL). Its indications have evolved with the adoption of pediatric-inspired protocols, refined risk stratification based on minimal residual disease (MRD), the identification of high-risk genetic subtypes, and the emergence of novel immunotherapies. Agents such as blinatumomab and inotuzumab ozogamicin can induce deep remissions and increasingly challenge traditional transplant algorithms. Chimeric antigen receptor T cell (CAR T-cell) therapies further reshape post-relapse strategies, while advances in conditioning regimens and donor selection have broadened allo-HSCT applicability. Current evidence supports allo-HSCT in patients with high-risk features or persistent MRD, though its benefit is increasingly debated in MRD-negative responders. This review synthesizes evolving data on indications, timing, modalities, and outcomes of allo-HSCT in adult ALL and highlights the need for personalized, MRD and genomics-guided approaches to optimize cure while minimizing transplant-related risks in the immunotherapy era.