Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants.
Male recipients of transplants from female (F-->M) hematopoietic stem cell donors represent a special group in whom donor T cells that are specific for recipient minor histocompatibility antigens encoded by Y-chromosome genes may contribute to a graft-versus-leukemia (GVL) effect and to graft-versus-host disease (GVHD). We examined the contribution of donor/patient sex to the risk for relapse and GVHD in 3238 patients who underwent HLA-identical sibling hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies at a single institution. Compared with other sex combinations, male recipients of female transplants had the lowest risk for relapse and the greatest odds for GVHD. Remarkably, after controlling for GVHD as a time-dependent covariate, F-->M HSCT still exhibited a lower risk for relapse than other sex combinations, demonstrating a selective GVL effect distinct from that contributed by GVHD. A reduction in relapse after F-->M HSCT was observed in patients with chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL). Taken together, these data suggest that minor H antigens encoded or regulated by genes on the Y chromosome contribute to a selective GVL effect against myeloid and lymphoid leukemias after F-->M HSCT.
Randolph
Sophia S B
SS
Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Gooley
Theodore A
TA
Warren
Edus H
EH
Appelbaum
Frederick R
FR
Riddell
Stanley R
SR
D000208:Acute Disease; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D012008:Recurrence; D012727:Sex Characteristics; D015996:Survival Rate; D014019:Tissue Donors
D006680:HLA Antigens