Unlikely identification of an 8/8 OR 10/10 matched donor for patients with uncommon haplotypes

Abstract

Aim Despite over 6 million subjects contributing to the NMDP HLA haplotype frequency reference data (HFD), haplotypes cannot be predicted from the HLA assignments of some patients searching for an unrelated donor (URD) in the Be The Match Registry®. The aims of this study were to determine the incidence of these patient searches and whether patient haplotypes lacking from the HFD can be found among the low-resolution typed URD pool. Methods From March 2014–2015, USA transplant centers submitting new NMDP searches with uncommon patient haplotypes (UPH), defined as a lack of haplotype pairs in any single race group in the HFD based upon HLA-A–C–B–DRB1–DQB1, were identified. Laboratory verification of patients’ HLA assignments was requested. Up to 20 USA based NMDP potential 10/10 or 8/8 donors were typed per patient to determine the likelihood of an allele match. Results The incidence of patient searches without pairs in a single race group in the HFD was 1.2% (144 of 12172 preliminary searches). Of the 144 patients, 27 had two haplotypes projected in disparate race tables, while 117 (81%) had at least one uncommon haplotype previously uncharacterized in the HFD. Non-White patients had the highest incidence of UPH. No patients with UPH had a 10/10 donor identified. Five patients, all with uncommon DRB1–DQB1 associations, had 8/8 donors identified (i.e., DQ mismatched). Conclusions HLA HFD that supports the HapLogic? matching algorithm is comprehensive as UPH patient searches were infrequent. Since these patients are unlikely to have a fully 10/10 matched donor identified, alternative stem cell sources including cord blood or a mismatched URD should be identified early in the search process. Many instances of typing corrections after initial HLA entry emphasize the importance of verifying the unique HLA assignments of these patients. UPH patients with haplotypes identified in disparate race groups but no pairs in a single race group highlights the need to better characterize patient HLA and mixed race/ethnicity for URD searching. Download : Download full-size image