Deletion of Y chromosome before allogeneic hematopoietic stem cell transplantation in male recipients with female donors

Abstract

The graft-versus-leukemia (GVL) effect is one of the curative mechanisms of allogeneic hematopoietic stem cell transplantation (allo-HCT). H-Y antigens, which are encoded by Y chromosome, are important targets of the GVL effect. Thus, deletion of the Y chromosome (del[Y]) might cause the GVL effect to deteriorate in a transplantation involving a female donor and male recipient, although the clinical significance of the del(Y) group remains to be elucidated. In this study, we evaluated adult male patients who underwent allo-HCT between 2010 and 2019 in Japan. There were 155 cases in the del(Y) group and 4149 cases without del(Y) who underwent female-to-male allo-HCT. Del(Y) was significantly associated with inferior overall survival (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.00-1.53; P = .049) and an increased risk of relapse (HR, 1.40; 95% CI, 1.08-1.80; P = .0098) in multivariate analyses. There was no significant difference in nonrelapse mortality between recipients with and without del(Y) (HR, 1.08; 95% CI, 0.769-1.51; P = .67). In contrast, del(Y) was not significantly associated with any clinical outcomes in the cohort of male-to-male allo-HCT. A higher incidence of relapse might have been caused by attenuation of the GVL effect resulting from a lack of H-Y antigens. Because a GVL effect resulting from sex mismatch may not be expected in men with del(Y) who undergo allo-HCT with a female donor, additional post–allo-HCT strategies might be required to prevent disease relapse.

Impact of anti-thymocyte globulin on survival outcomes in female-to-male allogeneic hematopoietic stem cell transplantation

“…On the other hand, some previous studies showed a reduced incidence of relapse which suggested the existence of a GVL effect due to sex-mismatch 8 , 24 – 26 . In fact, we previously reported that male recipients with deletion of Y-chromosome who underwent allo-HCT from a female donor showed a higher incidence of relapse 12 , suggesting attenuation of the GVL effect due to the loss of Y-chromosome. Thus, we initially hypothesized that the addition of ATG may contribute to a lower incidence of chronic GVHD and a higher incidence of relapse in female-to-male allo-HCT.…”

“…It may be reasonable to try to improve the survival inferiority of female-to-male allo-HCT by intensive GVHD prophylaxis. However, since previous reports have suggested a relationship between H-Y antigens and a graft-versus leukemia (GVL) effect 10 , 12 , an escalation of GVHD prophylaxis might induce an increased incidence of relapse in addition to infectious complications. We hypothesized that the use of ATG in female-to-male allo-HCT may contribute to a lower incidence of chronic GVHD and a higher incidence of relapse, and the prognosis in female-to-male allo-HCT may depend on which of these effects is predominant.…”

Impact of anti-thymocyte globulin on survival outcomes in female-to-male allogeneic hematopoietic stem cell transplantation

“…On the other hand, some previous studies showed a reduced incidence of relapse which suggested the existence of a GVL effect due to sex-mismatch 8, [23][24][25] . In fact, we previously reported that male recipients with deletion of Y-chromosome who underwent allo-HCT from a female donor showed a higher incidence of relapse 12 , suggesting attenuation of the GVL effect due to the loss of Y-chromosome. Thus, we initially hypothesized that the addition of ATG may contribute to a lower incidence of chronic GVHD and a higher incidence of relapse in female-to-male allo-HCT.…”