Advances in the genomics of allogeneic haemopoietic stem cell transplantation

Allogeneic haemopoietic stem cell transplantation is curative for many patients with haematologic disorders. Despite advances in supportive care, complications such as graft-versus-host disease (GVHD) and infection remain important causes of morbidity and mortality after transplantation. Human leukocyte antigen (HLA) matching of donors and recipients is important but does not avoid these complications. Recent studies have shown that non-HLA genetic polymorphisms influence the risk of complications after transplant. Polymorphisms in the genes encoding mediators and targets of GVHD, such as cytokines, adhesion molecules, and minor histocompatibility antigens, are associated with GVHD risk and severity. Particularly in HLA-mismatched transplants, matching of donors and recipients for natural killer cell receptors and ligands may influence disease relapse and survival. Polymorphisms in drug-metabolizing enzymes influence toxicities of immunosuppressive drugs used in transplant protocols. Finally, polymorphisms in mediators of host defence such as mannose-binding lectin, myeloperoxidase, and immunoglobulin receptors influence host immune reconstitution and infection risk after transplant. This novel genetic information offers the opportunity to better predict the risk of complications, to offer intensified immunosuppression to those at highest risk of GVHD, and to intervene with novel therapies. (C) 2004 Wiley-Liss, Inc.