Genomics of unrelated-donor hematopoietic cell transplantation

Unrelated-donor hematopoietic cell transplantation is a proven curative mod ality for hematologic malignancies. The success of unrelated-donor transpla ntation has been achieved through a better understanding of the immunobiolo gy of the HLA system and through more precise and comprehensive matching of donors and recipients. The extensive polymorphism of HLA genes confers imp ortant biological implications affecting engraftment, graft-versus-host dis ease and overall survival. Although more-complete HLA identity of the donor and recipient is associated with optimal transplant outcome, new informati on suggests that not every HLA disparity is functionally relevant. Future a dvances in unrelated-donor transplantation must include the identification of tolerable HLA mismatches, so that more patients may benefit from this th erapeutic modality. Furthermore, the role of cytokine-gene polymorphisms an d minor histocompatibility genes in transplant outcome requires investigati on. Delineation of the function of these markers as transplantation determi nants may provide alternative means for optimizing the results of hematopoi etic cell transplantation.