Transplant in ALL: who, when, and how?

Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a cornerstone in the treatment of high-risk acute lymphoblastic leukemia (ALL), yet optimal patient selection is challenging in the era of rapidly changing modern therapy. Refined molecular characterization allows for better risk assessment, sparing low-risk patients from allo-HCT toxicity while identifying those who may benefit from intensified approaches. Measurable residual disease (MRD) has emerged as a powerful predictor of relapse irrespective of treatment strategy, challenging the necessity of transplant in MRD-negative patients. Further, expanded donor options, particularly haploidentical transplantation coupled with reduced intensity conditioning, have extended the applicability of allo-HCT to a broader range of patients. Finally, immunotherapies and targeted treatments are increasingly integrated into both initial and relapsed treatment protocols yielding deep remission and allowing for successful transplant in patients with a history of advanced disease. In this review, we provide an overview of the contemporary role of transplant in adult patients with ALL, focusing on indications for allo-HCT in first remission, optimal sequencing of transplant with novel therapies, and advancements in donor selection and conditioning regimens.