title: Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy.
abstract: Sex-mismatched hematopoietic cell transplantation is linked to increased graft-versus-host disease and mortality in myeloablative conditioning. Here we evaluated outcomes of 1,041 adult transplant recipients at two centers between 2006 and 2013 and investigated how the effect of sex-mismatching differed in myeloablative, reduced-intensity, and non-myeloablative total lymphoid irradiation with anti-thymocyte globulin conditioning. Among patients who underwent myeloablative conditioning, male recipients with female donors had increased chronic graft-versus-host disease (hazard ratio 1.83, P<0.01), increased non-relapse mortality (hazard ratio 1.84, P=0.022) and inferior overall survival (hazard ratio 1.59, P=0.018). In contrast, among patients who received reduced-intensity conditioning, male recipients with female donors had increased acute graft-versus-host disease (hazard ratio 1.96, P<0.01) but no difference in non-relapse mortality or overall survival. Among the patients who underwent total lymphoid irradiation with anti-thymocyte globulin, male recipients with female donors showed no increase in graft-versus-host disease or non-relapse mortality. Notably, only in the cohort receiving total lymphoid irradiation with anti-thymocyte globulin were male recipients with female donors significantly associated with reduced relapse (hazard ratio 0.64, P<0.01), and allo-antibody responses against H-Y antigens were predictive of reduced relapse. In the cohort given total lymphoid irradiation with anti-thymocyte globulin, the graft-versus-leukemia effect resulted in superior overall survival in recipients of sex-mismatched grafts (HR 0.69, P=0.037). In addition, only in the cohort treated with total lymphoid irradiation with anti-thymocyte globulin were female recipients with male donors associated with reduced relapse (hazard ratio 0.59, P<0.01) and superior survival (hazard ratio 0.61, P=0.014) compared with sex-matched pairs. We conclude that the risks and benefits of sex-mismatched transplants appear to differ according to conditioning strategy and this could affect donor selection.
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakasone
authors.affiliation: Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.affiliation: Department of Health Research and Policy, Stanford University School of Medicine, CA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden Science for Life Laboratory, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Brodin
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Bita
authors.initials: B
authors.lastname: Sahaf
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lowsky
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Negrin
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Miklos
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA evmeyer@stanford.edu.
authors.forename: Everett
authors.initials: E
authors.lastname: Meyer
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality* / Q000628:therapy; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D008297:Male; D036102:Peripheral Blood Stem Cell Transplantation; D012737:Sex Factors; D015996:Survival Rate; D019172:Transplantation Conditioning; D061349:Unrelated Donors