HapLogic: A Predictive Human Leukocyte Antigen–Matching Algorithm to Enhance Rapid Identification of the Optimal Unrelated Hematopoietic Stem Cell Sources for Transplantation

Abstract

The search for a suitable human leukocyte antigen (HLA)-matched unrelated adult stem cell donor (URD) or umbilical cord blood unit (UCB) is a complex process. The National Marrow Donor Program (NMDP) developed a search algorithm known as HapLogic, which is currently provided within the NMDP Traxis application. The HapLogic algorithm has been in use since 2006 and has advanced URD/UCB HLA-matching technology. The algorithm has been shown to have high predictive accuracy, which can streamline URD/UCB selection and drive efficiencies in the search process to the benefit of the stem cell transplantation community. Here, we describe the fundamental components of the NMDP matching algorithm, output, validation, and future directions.

Next generation sequencing characterizes HLA diversity in a registry population from the Netherlands

“…This international exchange is facilitated by a global database of volunteer donor HLA phenotypes and international cooperation among world‐wide registries . Because of changes in the methods and resolution of HLA typing of registry donors over time and to support search, algorithms have been developed to predict which incompletely typed donors might match the searching patient when typed at high resolution . These algorithms base their predictions on the frequency of haplotypes in the unrelated donor population.…”

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

“…Our centers frequently prioritize a CB graft over a 7/8 HLA-matched URD and this practice is strongly supported by single center analyses 4,6,8 . Knowledge of the patient’s ancestry, use of computerized programs based upon population haplotype frequencies (eg the NMDP’s Haplogic and search prognosis tool 31,32 and consultation with HLA experts can rapidly determine the likelihood of identifying an 8/8 HLA-matched URD as soon as the recipients HLA-typing and preliminary search results are obtained. Since prolonged URD searches and donor drives are very unlikely to result in the acquisition of a suitably matched URD if one is not identified within the first days-weeks of search initiation, futile URD searches must be avoided with timely consideration of other stem cell sources.…”

HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities

“…67 Thus, by applying the concept of permissive TCE matching, the chances of finding an "intelligently" mismatched UD has significantly increased, and online bioinformatics tools have been made available by donor registries in the United States and Europe to facilitate TCE selection in clinical practice. [68][69][70] Concomitantly, requests for HLA-DPB1 typing upfront in clinical UD searches through the NMDP have greatly increased from 11% to 57% over the last decade (Jason Dehn, NMDP, personal communication, 6 March 2017). Recently, it was shown that the in silico assignment of HLA-DPB1 alleles to TCE groups can be performed based on their overall "functional distance" (FD) score, that is, the median impact of 12 key amino acid polymorphisms on T-cell alloreactivity.…”