Myeloablative sibling-matched allogeneic transplantation for adult acute lymphoblastic leukaemia provides the best outcome, but most patients lack a suitable, related histocompatible donor. We reviewed three haematopoietic stem cell donor sources used for alternative donor transplantation pointing out drawbacks of these approaches including inherent selection bias. Matched unrelated donor allografts most often are performed in Philadelphia chromosome-positive disease and in second complete remission (CR2); a nearly 30% event-free survival (EFS) can be anticipated in select patients. Transplants using haploidentical donors are most successful if undertaken in CR1 and CR2 and appear to produce EFS rates of about 25%. Limited umbilical cord blood transplant data suggest efficacy, but marked patient and treatment heterogeneity hamper conclusions. Each of these three strategies has unique potential benefits and disadvantages. The growing use of minimal residual disease detection may identify subgroups of patients unlikely to be cured by chemotherapy alone; these patients are candidates for upfront high-dose chemoradiotherapy and cellular immunotherapy. These three approaches are plagued by treatment-related mortality and relapse rates as high as 40%, but advances in technology and supportive care may make each stem cell source more feasible and efficacious.
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