Young Female Donors Do Not Increase the Risk of Graft-versus-Host Disease or Impact Overall Outcomes in Pediatric HLA-Matched Sibling Hematopoietic Stem Cell Transplantation

Abstract

Optimal donor selection is critical in hematopoietic stem cell transplantation (HSCT). Donor-recipient sex mismatch, donor age, and female donor-donor parity are known to impact graft-versus-host disease (GVHD) and outcomes in adults. Minor histocompatibility antigens encoded by the human Y chromosome can result in specific antibody formation in some female donors, may increase in frequency with increasing donor age, and may be contributory to the increased incidence of GVHD. To better understand the role of donor age/sex and sex matching in HSCT outcomes, we conducted a retrospective study of pediatric patients receiving their first myeloablative sibling donor HSCT (n = 244) from 1998 to 2012. Observed rates of GVHD were low: 17% of patients surviving past engraftment (n = 243) developed grades II to IV acute GVHD (aGVHD) and 14% surviving ≥ 100 days (n = 229) developed chronic GVHD (cGVHD). On multivariate analysis the risk of aGVHD, cGVHD, and death increased with patient age as expected. Female donor sex and sex mismatch (female donor-male recipient) had no impact on the development of aGVHD. cGVHD was increased with female donors only if the donor was ≥12 years old. No cGVHD was observed among 109 patients aged < 10 years who received a 6/6 HLA-matched marrow HSCT, regardless of donor age or sex. Survival was mostly driven by diagnosis. Results suggest that in pediatric HSCT, young HLA-matched siblings are equivalently good donors regardless of sex or donor-recipient sex mismatch.

Allogeneic hematopoietic stem cell transplantation from matched related donors for acute myeloid leukemia

“…8). Despite some literature data on the higher risk of GvHD and mortality associated with allogeneic HSCT in patients transplanted from women (13,14,15), in our group as well as in some other studies (16,17,18), there was no effect on overall survival. In our study, patients who received a graft from a sister achieved a better OS, yet the difference is not statistically significant (Fig.…”

Outcome of Donor and Recipient Sex Match Versus Mismatch in Stem Cell Transplant Procedure

“…These results are in contrast to previous studies which have reported that sex mismatch transplants have the highest odds of developing GvHD due to the GvL effect [14,15]. However Friedrich et al reported no evidence of chronic GvHD in young donors who received a sex mismatched but 6/6 HLA-matched donor grafts [16]. Our cohort was similar to this as median age in our patients was 18 years and majority were complete HLA matched with their donors.…”

The impact of donor-recipient sex matching on transplant-related complications in children after allogeneic haematopoietic stem cell transplantation – a single-centre, retrospective study

“…The presented study showed no correlation between donors' and recipients' genders and frequency of HSCT complications in children. There were no statistically significant differences in the prevalence of adverse events between all four groups, which corresponds with the findings of the latest study of 244 paediatric patients undergoing MSD HSCT, presented by Friedrich et al in 2018 [7]. Rising evidence of lack of direct impact of sex-mismatching on overall HSCT transplant complications and outcomes in the paediatric population might in the future change the criteria we follow when looking for potential donors.…”