Race and Survival in Unrelated Hematopoietic Cell Transplantation

Abstract

Survival after hematopoietic cell transplantation depends on race/ethnicity and histocompatibility (HLA) between the patient and transplant donor. HLA sequence variation is a genetic construct of continental populations, but its role in accounting for racial disparities of transplant outcome is unknown. To determine disparities in transplant survivorship among patients of diverse race while accounting for patient and donor HLA variation. A total of 26,945 self-described Japanese, U.S. Asian, White, Hispanic, and Black patients received an unrelated donor transplant for the treatment of a life-threatening blood disorder. The risk of mortality with and without adjustment for known HLA risk factors (number and location of donor mismatches; patient HLA-B leader genotype and HLA-DRβ peptide-binding motif) was studied using multivariable models. Survival after HLA-matched transplantation for patients with optimal leader and peptide-binding features was estimated for each race, as was the improvement in survival over calendar-year time by considering year of transplantation as a continuous linear variable. The number, location, and nature of donor HLA mismatches and the frequency of patient HLA-B and HLA-DRB1 sequence motifs differed by race. Japanese patients had superior survival compared to other races without consideration of HLA. After HLA adjustment, three mortality risk strata were identified: Japanese and U.S. Asian (low-risk); White and Hispanic (intermediate-risk), and Black patients (high-risk). Survival for patients with optimal donor and HLA characteristics was superior for Japanese, intermediate for U.S. Asian, White, and Hispanic, and lowest for Black patients. Five-year increments of transplant year were associated with greater decreases in mortality hazards for Black and Hispanic patients than for Japanese, U.S. Asian and White patients. Transplant survivorship disparities are influenced by HLA as a genetic construct of race. A more complete understanding of the factors that influence transplant outcomes provides opportunities to narrow disparities for future patients.

Keywords: Ancestry; HLA; Hematopoietic cell transplantation; Race; Unrelated donor.