Use of alternative donors for allogeneic stem cell transplantation.

For patients without a human leukocyte antigen (HLA)-matched sibling or unrelated donor, options include transplantation from HLA-mismatched related donors, HLA-mismatched unrelated donors, or unrelated cord blood units. Graft failure remains a problem in 10%-20% of cord blood transplants that contain a limited number of hematopoietic cells. Many approaches are tested in clinical trials to offset the risk of graft failure after cord blood transplantation. GVHD remains a hurdle with any HLA mismatched graft. The use of post-transplant cyclophosphamide holds the promise to overcome the HLA barrier and prevent GVHD despite donor mismatch for a full HLA haplotype. Priority should be given to enrolling patients onto transplant protocols addressing the fundamental problems of engraftment, GVHD, relapse or treatment-related mortality tested with one or more of the alternative stem cell sources. Principles for prioritization of alternative stem cell sources are discussed separately for children and adults who cannot be enrolled on clinical trials. It is difficult ranking currently available sources in the face of multiple factors affecting outcomes, rapidly changing transplant technology and without results from comparative trials.