Allele-level HLA matching for umbilical cord blood transplantation for non-malignant diseases in children: a retrospective analysis

Summary Background The standard for selecting unrelated umbilical cord blood units for transplantation for non-malignant diseases relies on antigen-level (lower resolution) HLA typing for HLA-A and HLA-B, and allele-level for HLA-DRB1. We aimed to study the effects of allele-level matching at a higher resolution—HLA-A, HLA-B, HLA-C, and HLA-DRB1, which is the standard used for adult unrelated volunteer donor transplantation for non-malignant diseases—for umbilical cord blood transplantation. Methods We retrospectively studied 1199 paediatric donor-recipient pairs with allele-level HLA matching who received a single unit umbilical cord blood transplantation for non-malignant diseases reported to the Center for International Blood and Marrow Transplant Research or Eurocord and European Group for Blood and Marrow Transplant. Transplantations occurred between Jan 1, 2000, and Dec 31, 2012. The primary outcome was overall survival. The effect of HLA matching on survival was studied using a Cox regression model. Findings Compared with HLA-matched transplantations, mortality was higher with transplantations mismatched at two (hazard ratio [HR] 1·55, 95% CI 1·08–2·21, p=0·018), three (2·04, 1·44–2·89, p=0·0001), and four or more alleles (3·15, 2·16–4·58, p 7 cells per kg compared with 21 × 10 7 cells per kg or less (HR 1·47, 1·11–1·95, p=0·0076), and transplantations done in 2000–05 compared with those done in 2006–12 (HR 1·64, 1·31–2·04, p Interpretation These data support a change from current practice in that selection of unrelated umbilical cord blood units for transplantation for non-malignant diseases should consider allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1. Funding National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute for Allergy and Infectious Diseases; US Department of Health and Human Services—Health Resources and Services Administration; and US Department of Navy.