Frequencies and haplotype associations of non-expressed HLA alleles in ethnically diverse populations on the National Marrow Donor Program's Be The Match Registry.

HLA allele matching is critical to successful bone marrow transplantation between a patient and donor. Non-functional HLA alleles, so called 'null alleles', are not well described within a large population of well HLA-typed ethnically diverse individuals despite their impact on donor selection. A retrospective analysis was performed on 833,789 unrelated donors (URDs) in the National Marrow Donor Program's Be The Match Registry® typed for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 by next-generation DNA sequencing. Results showed that null alleles occur in low frequency (2.30E-04) compared to expressed alleles. Their overall frequency ranged from 6.00E-07 to 9.25E-04 with a median of 1.20E-06. The expected allele associations were commonly observed for HLA-A*24:09N, HLA-B*51:11N, and HLA-C*04:09N; however, associations outside of the expected were also observed. Notably, 82% of the National Marrow Donor Program Registry URDs carrying HLA-A*24:11N showed a different HLA-C allele association, HLA-C*05:01, compared to the allele described by prior published work characterizing German donor populations, HLA-C*04:01. The frequencies of these observed null alleles and linkage disequilibrium information could be invaluable and helpful in guiding the HLA testing decisions.

Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.

CD34+ cell content of 126 341 cord blood units in the US inventory: implications for transplantation and banking.

CD34+ cell dose is critical for cord blood (CB) engraftment. However, the CD34+ content of the CB inventory in the United States is unknown. We examined the CD34+ cell content of 126 341 red blood cell-depleted US units banked from January 2007 to September 2017 with a total nucleated cell (TNC) count of ≥90 × 107 and a cryovolume of 24-55 mL. Median pre-cryopreservation TNC content was 127 × 107 (interquartile range [IQR], 108-156 × 107); CD34+ cell content was 44 × 105 (IQR, 29 to 67 × 105). The median CD34+:TNC ratio was 0.34%. TNC and CD34+ cell content correlation was weak (r = 0.24). Of 7125 units with TNCs of ≥210 × 107, only 47% had CD34+ content of ≥100 × 105 However, some units had high CD34+ content for a given TNC count. Only 4% of CB units were acceptable as single-unit grafts (TNCs, ≥2.5 × 107/kg; CD34+ cells, ≥1.5 × 105/kg) for 70-kg patients; 22% of units were adequate for 70-kg patients using lower dose criteria (TNCs, ≥1.5 × 107/kg; CD34+ cells, ≥1.0 × 105/kg) suitable for a double-unit graft. These findings highlight that units with the highest TNC dose may not have the highest CD34+ dose, units with unexpectedly high CD34+ content (a ratio of >1.0%) should be verified, and the US CB inventory of adequately sized single units for larger patients is small. They also support the ongoing use of double-unit grafts, a focus on banking high-dose units, and development of expansion technologies.

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

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.