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, reducedintensity, 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 antithymocyte 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. Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nH. Nakasone et al. 1478haematologica | 2015; 100 (11) factors and disease status are among the major drivers determining the conditioning intensity for HLA-matched or single-allele mismatched transplantation. In general, after selection of conditioning, if multiple potential donors are available, other factors such as blood type and sex of the donor versus recipient are evaluated. To determine a potential effect of sex-mismatching within each conditioning type, we evaluated the outcomes of 1,041 adult recipients at two centers between 2006 and 2013. We found that the impact of sex-mismatched transplants differs according to conditioning strategy. Myeloablative conditioned, sex-mismatched Female→Male patients showed increased non-relapse mortality and reduced overall survi...

Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

“…In contrast, the impact of sex mismatch is a matter of debate, with conflicting results. These might reflect different definitions of sex mismatch, which has been considered only for male recipient as in our study [20][21][22] or for both male and female in others [17]. Interestingly, all 3 studies confining sex mismatch to male recipients reported a significant impact for this variable similar to our findings, albeit possibly dependent on conditioning regimen.…”

“…Transplants of male patients from female donors (sex mismatch) has been associated with poorer outcome [20][21][22]. We therefore investigated the relevance of sex mismatch relative to HLA mismatching in the subgroup of male patients who received transplants from 10/10 MUDs or 9/10 MMUDs.…”

The association between blood donor sex and age and transfusion recipient mortality: an exploratory analysis

“…Our approach for categorizing donor exposure used “exclusive” categories, which allowed us to use all the data in every model, avoiding the need to exclude individuals and carry out subgroup analyses where groups are formulated based on the number of RBC transfusions. Given the established role of donor factors on outcomes in patients receiving stem cell transplants and other solid‐organ transplants, equipoise persists regarding the potential harms of transfusion associated with donor sex and age, and further studies are needed …”

“…Several hypotheses have been suggested, including the hormonal effect on RBC rigidity and oxygen‐carrying capacity and an immunological/inflammatory effect on the patient after receiving RBCs from a previously pregnant female donor . Nevertheless, in solid organ and hematopoietic stem cell transplantation, donor age and sex are established factors that can impact patient outcomes and influence donor selection …”

Stem cell transplantation during cancer

“…According to literature 25% of siblings may statistically be a matched donor and in 30% of all patients a suitable related donor could indeed be found (12). A sibling donor is the first choice and, if possible, a male donor is usually a preferred choice (13). For the remaining two thirds of the patients a donor may be available through the international donor registries.…”