Risk assessment in haematopoietic stem cell transplantation: Impact of donor-recipient sex combination in allogeneic transplantation

In allogeneic transplantation the donor-recipient sex combination plays a role in outcome. In large retrospective registry studies of several thousands of patients with aplastic anemia, chronic myelocytic leukemia (CML), acute myelocytic leukemia (AML), and multiple myeloma, chronic graft-versus-host disease (cGVHD) was more frequent and transplant-related mortality (TRM) higher in males with a female donor (F -> M) than in other donor-recipient sex combinations. Graft rejection was more frequent in females with a male donor (M -> F) in aplastic anemia, and a graft-versus-tumor effect (GVT) was documented as a reduced relapse rate in F -> M in CML, AML and multiple myeloma. The overall survival was adversely affected in F -> M in aplastic anemia, AML and CML and in M -> F in aplastic anemia. These results support the view that donor T cells specific for male minor histocompatiblity antigens encoded by Y-chromosome genes contribute to GVHD, graft rejection, GVT and survival in sex-mismatched transplants.