Female Sex is Associated with Improved Long-Term Survival Following Allogeneic Hematopoietic Stem Cell Transplant.

Abstract

BACKGROUND\nLife expectancy for long-term survivors of allogeneic hematopoietic stem cell transplant (alloHSCT), defined as those living ≥5 years post-transplant, is significantly lower compared to that of the age-matched general population despite a relatively low primary disease relapse rate >2 years post-transplant. Among several factors, patient sex is increasingly recognized as a prognostic indicator of long-term survival.\n\n\nOBJECTIVE\nWe examined the influence of patient sex and donor-recipient sex matching on overall survival in a landmark analysis of long-term survivors.\n\n\nSTUDY DESIGN\nUsing our institutional database supplemented with individual patient record review, we retrospectively investigated the relative influence of recipient sex and donor-recipient sex matching on outcomes of long-term survivors receiving alloHSCT between 1994 - 2014.\n\n\nRESULTS\nOver this 20-year period, 247 met inclusion criteria for analysis; males and females had similar demographic and treatment characteristics. However, significantly more deaths after the 5-year landmark occurred in male recipients. Interestingly, donor sex did not have a significant impact on overall survival in multivariate analysis, and differences in overall survival of donor-recipient sex pairs was driven by recipient sex. In addition to recipient sex, only cGVHD retained significance as a covariate with impact on overall survival in multivariate analysis. Men experienced slightly higher, but non-significant, rates and increased severity of cGVHD, and a greater percentage of cGVHD-related mortality as compared to females.\n\n\nCONCLUSION\nIn this long-term survival analysis of alloHSCT adult patients, one of the only to include follow-up to 15 years, our results show that women survive significantly longer than men irrespective of their age at transplant. This outcome is independent of other common pre-transplant prognostic indicators such as donor sex or performance status at transplant. Inferior survival for males is consistent with survival outcomes described in transplant literature. Gathering evidence suggests a biologic basis for long-term sex-determined outcomes, possibly due to differing rates or severity of cGVHD or sustained alloimmune tolerance in females. Larger studies are warranted to validate these retrospective clinical results.