Efficiency of HLA-A, -B, -C, -DRB1 High-Resolution Typings of Newly Recruited Potential Stem Cell Donors.
Authors: Schmidt Alexander H. , Stahr Andrea , Baier Daniel , Ehninger Gerhard , Rutt Claudia 
Published: October 2019

Abstract
In strategic stem cell donor registry planning, it is of special importance to decide how to type newly registered donors. This question refers to both the selection of HLA loci and the resolution (low, intermediate, or high) of HLA typings. In principle, high-resolution typings of all transplant-relevant loci are preferable. However, cost considerations generally lead to incomplete typings (only selected HLA loci with low or intermediate typing resolution) in practice.
Here, we present results of a project in which newly recruited donors are typed for the HLA-A, -B, -C, and -DRB1 loci with high resolution by sequencing. Efficiency of these typings is measured by subsequent requests for confirmatory typings (CTs) and stem cell donations. Results for donors who were included in the project (Donor Group A) are compared to requests for donors with other, less complete typing levels: HLA-A and HLA-B at intermediate resolution, HLA-DRB1 at high resolution (Group B); HLA-A, -B, -C, and -DRB1 at intermediate resolution (Group C); HLA-A, -B, and -DRB1 at intermediate resolution (Group D). All data are taken from the donor file of DKMS German Bone Marrow Donor Center. Since the four groups differ considerably regarding their age and sex distributions, calculations are also carried through for restricted data sets that include only male donors up to age 25.
Results are shown in Table 1. Donors of Groups A and B have similar CT request frequencies of 5.90 and 5.92 requests per 100 donors per year in the resctricted data sets, respectively. These frequencies significantly exceed the corresponding frequencies of the other groups with less complete typing levels. For donation requests, the frequency is signifcantly higher for Group A than for Group B (restricted data sets): 1.45 vs 1.02 requests per donor per year (p<0.05). Obviously, the additional HLA information for Group A donors leads to a higher ratio between donations and CT requests. Again, figures are much lower for Groups C and D. These results are based on a high number of requests even for the restricted data sets, namely between 44 and 90 donation requests and between 227 and 619 CT requests per group.
Our results show that full (HLA-A, -B, -C, and -DRB1) high-resolution typings at donor recruitment lead to significantly higher probabilities for donation requests. Donor centers and registries should carefully take into account these higher probabilities when they consider full high-resolution typings for newly recruited donors. However, the final decision regarding the typing strategy at recruitment must also depend on the individual cost structure of a donor center or registry. The presented results are based on a donor file that consists mainly (≈99%) of Caucasian donors. It should be subject to further analyses if these results also apply to other, more heterogeneous donor pools.
Table 1: Requests per 100 donors per year by donor group CT requests Donation requests Donor Group Full data set Only male donors≤ 25 Full data set Only male donors≤ 25 A 5.14 5.90 1.45 1.45 B 4.60 5.92 0.84 1.02 C 2.50 3.03 0.58 0.67 D 2.36 2.80 0.38 0.48