Genetics of allogeneic hematopoietic cell transplantation. Role of HLA matching, functional variation in immune response genes.

Successful outcome following hematopoietic stem cell transplantation (HSCT) is ultimately determined by the ability to achieve sustained engraftment and immune reconstitution, control of graft-versus-host disease (GVHD), and in patients with hematological malignancy the complete eradication of abnormal or malignant cells. GVHD, which can be a serious and fatal complication, is an immune reaction that is initiated by donor T cells in response to recipient alloantigens. Genetic variation in both patient and donor can significantly affect transplant outcome by causing disparity for transplant antigens, and by altering the function of immune response genes that control cellular activation and inflammation. Genetic variation can modulate the intensity of the alloimmune response, the risk of transplant-related organ toxicity and mortality, and may also affect the development of tolerance and the reconstitution of the immune system following HSCT.