Hematopoietic stem cell donor registry strategies for assigning search determinants and matching relationships

Abstract

Summary:Registries and cord blood banks around the world collect and store the HLA types of volunteers in order to identify matched unrelated donors for patients requiring hematopoietic stem cell transplantation. This task is complicated by the many formats in which HLA types are provided by the testing laboratories (types obtained by serology vs by DNA-based methods; high vs intermediate vs low resolution) and by the need to identify which of these diverse types are most likely to match the HLA assignments of a searching patient as closely as possible. Conversion of the assignments to 'search determinants' may be included within the algorithm used to select and prioritize a list of potentially suitable donors, either as an aid to matching or as a tool to optimize the performance of comparisons within large data files. The strategies used by registries to create search determinants are described. A set of search determinants, utilized by the National Marrow Donor Program, is provided as an example and is intended to initiate further discussion aimed at understanding the process used by each registry with the possibility of developing a standard process among registries worldwide. (Table 1). As the complexity of HLA nomenclature increases 1 and as registries seek to exchange information to facilitate the world-wide search for unrelated donors, 2-4 it becomes critically important to clarify and perhaps even standardize the types of HLA assignments that are accepted into a registry, how assignments are compared, and how potential donors are identified within each registry. This document provides guidelines and suggests strategies for comparing the HLA assignments in order to identify potentially matched donors for a specific patient. Issues involving the limitations in the approaches used to interpret primary typing data obtained from DNA assays and the complications that this creates for registries have already been discussed. 5-8 HLA assignments for donors and patientsUsually, HLA-A, -B, and -DR types are assigned for volunteer donors and patients seeking an unrelated donor, and search algorithms are based on matching only for these

HLA mismatching within or outside of cross-reactive groups (CREGs) is associated with similar outcomes after unrelated hematopoietic stem cell transplantation

“…18,19 For comparison and analysis of CREG matching, the high-resolution HLA data were converted to serologic equivalents. 20,21 The extents of allele matching for study populations are described in Tables 2-3.…”

HLA matching affects clinical outcome of adult patients undergoing haematopoietic SCT from unrelated donors: a study from the Gruppo Italiano Trapianto di Midollo Osseo and Italian Bone Marrow Donor Registry

“…Searching algorithms aim at finding the optimal match between the patient and the potential donor. 2 As the '10/10 matched' (that is, high-resolution identity at loci HLA-A, -B, -C, -DRB1 and -DQB1) donor is not always available, some extent of HLA mismatch (Mm) can be accepted; however, there is still some controversy about the precise impact of HLA mismatching on HSCT outcomes, because published reports indicate discordant results about the relative importance of loci involved. [3][4][5][6][7][8][9][10][11][12][13][14] A recent study by Lee et al 3 indicated that both class I and class II Mms affect survival, suggesting that each HLA Mm is associated with an additional unadjusted survival impairment of 9-10%.…”

World Marrow Donor Association guidelines for use of HLA nomenclature and its validation in the data exchange among hematopoietic stem cell donor registries and cord blood banks

“…These guidelines are firmly based on the nomenclature developed by the World Health Organization Nomenclature Committee for Factors of the HLA System 14 and uniformly accepted by the HLA community and on the requirements for presenting and condensing HLA data within the format of the registries' information systems. 8 A strategy for the latter has been in use for a long time, but neither specified nor standardized so far. Table 1 describes reference web sites that include relevant information for these guidelines.…”

“…Continuously updated lists of assignments and correspondences approved in the context of these guidelines will be maintained on two WMDA-specified reference web sites: the IMGT/HLA database for HLA nomenclature (www.anthonynolan.org.uk/HIG/nomen/wmda.html) 15 and the US National Marrow Donor Program web site for codes that include multiple allele alternatives (bioinformatics. nmdp.org/HLA/allele_codes_idx.html) 8 (Table 1). The latter site includes contact information for registry requests for 2.3.…”

“…To this end, the WMDA has established guidelines for the international exchange of hematopoietic progenitor cells 2,3 and its working groups have developed guidelines on ethical issues related to donation, [4][5][6] donor characterization and search algorithms, [7][8][9] and the logistics of the search process and progenitor cell transport. 10,11 Recently, standards for registries engaged in international exchange have been established and an accreditation program was begun in 2003.…”