Genomics of unrelated-donor hematopoietic cell transplantation

Unrelated-donor hematopoietic cell transplantation is a proven curative modality for hematologic malignancies. The success of unrelated-donor transplantation has been achieved through a better understanding of the immunobiology of the HLA system and through more precise and comprehensive matching of donors and recipients. The extensive polymorphism of HLA genes confers important biological implications affecting engraftment, graft-versus-host disease and overall survival. Although more-complete HLA identity of the donor and recipient is associated with optimal transplant outcome, new information suggests that not every HLA disparity is functionally relevant. Future advances in unrelated-donor transplantation must include the identification of tolerable HLA mismatches, so that more patients may benefit from this therapeutic modality. Furthermore, the role of cytokine-gene polymorphisms and minor histocompatibility genes in transplant outcome requires investigation. Delineation of the function of these markers as transplantation determinants may provide alternative means for optimizing the results of hematopoietic cell transplantation.