Stem cell transplantation for ALL: you've always got a donor, why not always use it?

Hematopoietic stem cell transplantation (HSCT) represents a consolidated therapeutic strategy for high-risk pediatric acute lymphoblastic leukemia (ALL), offering the potential for curative treatment. This manuscript delves into the debate around the more universal application of HSCT for pediatric ALL in the modern era, considering the ubiquitous availability of suitable donors. In fact, despite significant advancements in chemotherapy, targeted therapy, and immunotherapy, a subset of pediatric patients with ALL with high-risk features or relapse continue to encounter poor prognostic outcomes. For this subgroup of patients, HSCT often remains the only potentially curative measure, leveraging the graft-versus- leukemia effect for long-term disease control. Nevertheless, the procedure's complexity and associated risks have traditionally curtailed its widespread use. However, the scenario is shifting with improvements in HLA matching, availability of alternative donor sources, less toxic conditioning regimens, and improved supportive care protocols. Concurrently, emerging therapies like CD19+ CAR T cells present new considerations for definitive therapy selection in relapsed/ refractory ALL. This article reviews critical current evidence and debates the potential of HSCT as a more universal treatment for ALL, reevaluating traditional treatment stratification in light of the constant availability of stem cell donors.