Immunogenetics in stem cell donor registry work: The DKMS example (Part 1)

Abstract

Currently, stem cell donor registries include more than 35 million potential donors worldwide to provide HLA‐matched stem cell products for patients in need of an unrelated donor transplant. DKMS is a leading stem cell donor registry with more than 9 million donors from Germany, Poland, the United States, the United Kingdom, India and Chile. DKMS donors have donated hematopoietic stem cells more than 80,000 times. Many aspects of donor registry work are closely related to topics from immunogenetics or population genetics. In this two‐part review article, we describe, analyse and discuss these areas of donor registry work by using the example of DKMS. Part 1 of the review gives a general overview on DKMS and includes typical donor registry activities with special focus on the HLA system: high‐throughput HLA typing of potential stem cell donors, HLA haplotype frequencies and resulting matching probabilities, and donor file optimization with regard to HLA diversity.

Immunogenetics in stem cell donor registry work: The DKMS example (Part 2)

“…These savings enabled donor registries to grow faster than it would have been possible with the costs of Sanger‐based HLA typing. For example, the substantial acceleration of DKMS donor file growth since 2014 (Figure of Part 1 of this review; Schmidt et al, ) would not have been fundable without NGS‐related cost savings.…”

“…Massive cost reductions resulting from next‐generation sequencing (NGS)‐based HLA typing (Schmidt et al, ) enabled a substantial extension of the DKMS standard typing profile of new donors beyond HLA. This standard typing profile currently includes the following parameters beyond the six “classical” HLA loci (A, B, C, DRB1, DQB1, DPB1): ABO and Rh blood groups (Lang et al, ), Cytomegalovirus (CMV) Immunoglobulin G (IgG) serostatus (Behrens et al, ; full publication submitted), 16 KIR genes (Schmidt, Lange, Hofmann, Schetelig, & Pingel, ; Wagner et al, ), MICA/MICB (publication submitted), HLA‐E (Hofmann et al, ; full publication in preparation), HLA‐DRB3/4/5, HLA‐DQA1, and HLA‐DPA1 (since October 2019) and the C‐C motif chemokine receptor 5 Delta32 (CCR5∆32) deletion (Solloch et al, ). …”

“…Figure shows the cumulative and monthly numbers of samples from DKMS donors genotyped at DKMS Life Science Lab (LSL) for the various parameters. Based on the numbers given in Figure 5 of Part 1 of this review (Schmidt et al, ), we invest 25% of the cost savings due to the switch from Sanger sequencing‐based to NGS‐based HLA typing into typing profile extensions beyond the classical HLA loci. Reasons for including the various parameters in the standard donor typing profile can be divided in three groups:…”

“…We mentioned the well‐known positive impact of “complete” HLA typing (i.e. 4–6 classical HLA loci at high resolution) on donation probabilities in the first part of the review (Schmidt et al, , paragraph HLA typing: Classical HLA loci ). Here, we focus on the impact of donor age and gender and of CMV serotyping on donation probabilities.…”

“…This article is the second part of a two‐part review on topics from immunogenetics and population genetics that are related to the work of DKMS, a leading stem cell donor registry with more than 9.6 million donors in six countries. Part 1 of the review (Schmidt et al, ) covered typical donor registry activities closely related to the human leukocyte antigen (HLA) system, namely high‐throughput HLA typing of potential stem cell donors, HLA haplotype frequencies and resulting matching probabilities, and donor file optimization with regard to HLA diversity. In this second part of the review, we deal with non‐HLA donor parameters and DKMS activities beyond standard donor registry work: donor typing beyond the classical HLA loci, impact of non‐HLA parameters on donation probabilities, identification of novel HLA, killer cell immunoglobulin‐like receptor (KIR), and major histocompatibility complex (MHC) class I polypeptide‐related sequence A/B (MICA/MICB) alleles, the setup and activities of the Collaborative Biobank coordinated by DKMS and pharmacogenetics in the donor registry context.…”