Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched related hematopoietic stem cell transplants
From the Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA; and the Department of Medicine, University of Washington School of Medicine, Seattle.4ti, http://www.100md.com
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.(Sophia S. B. Randolph Theodore A. Gooley Edus H. Warren Frederick R. Appelbaum and Stanley R. Riddel)
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.(Sophia S. B. Randolph Theodore A. Gooley Edus H. Warren Frederick R. Appelbaum and Stanley R. Riddel)