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

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.