Better allele-level matching improves transplant-related mortality after double cord blood transplantation

Cord blood transplant requires less stringent human leukocyte antigen matching than unrelated donors. In 133 patients with hematologic malignancies who engrafted after double cord blood transplantation with a dominant unit, we studied the effect of high resolution testing at 4 loci (-A, -B, -C, -DRB1) for its impact on 2-year transplant-related mortality. Ten percent of the dominant cord blood units were matched at 7-8/8 alleles using HLA-A, -B, -C, and -DRB1; 25% were matched at 6/8, 40% at 5/8, and 25% at 4/8 or less allele. High resolution typing at 4 loci showed that there was no 2-year transplant-related mortality in 7-8/8 matched patients. Patients with 5-6/8 matched dominant cord blood units had 2-year transplant-related mortality of 39% while patients with 4/8 or less matched units had 60%. Multivariate regression analyses confirmed the independent effect of high resolution typing on the outcome when adjusted for age, diagnosis, CD34(+) cell dose infused, graft manipulation and cord to cord matching. The worst prognostic group included patients aged over 32 years with 4/8 or less matched cord blood units compared with patients who were either younger than 32 years old independent of allele-level matching, or aged over 32 years but with 5-6/8 matched cord blood units (Hazard Ratio 2.2; 95% confidence interval: 1.3-3.7; P<0.001). Patients with 7-8/8 matched units remained the group with the best prognosis. Our data suggest that high resolution typing at 4 loci and selecting cord blood units matched at at least 5/8 alleles may reduce transplant-related mortality after double cord blood transplantation.