A comparative reference study for the validation of HLA-matching algorithms in the search for allogeneic hematopoietic stem cell donors and cord blood units.

The accuracy of human leukocyte antigen (HLA)-matching algorithms is a prerequisite for the correct and efficient identification of optimal unrelated donors for patients requiring hematopoietic stem cell transplantation. The goal of this World Marrow Donor Association study was to validate established matching algorithms from different international donor registries by challenging them with simulated input data and subsequently comparing the output. This experiment addressed three specific aspects of HLA matching using different data sets for tasks of increasing complexity. The first two tasks targeted the traditional matching approach identifying discrepancies between patient and donor HLA genotypes by counting antigen and allele differences. Contemporary matching procedures predicting the probability for HLA identity using haplotype frequencies were addressed by the third task. In each task, the identified disparities between the results of the participating computer programs were analyzed, classified and quantified. This study led to a deep understanding of the algorithms participating and finally produced virtually identical results. The unresolved discrepancies total to less than 1%, 4% and 2% for the three tasks and are mostly because of individual decisions in the design of the programs. Based on these findings, reference results for the three input data sets were compiled that can be used to validate future matching algorithms and thus improve the quality of the global donor search process.

Cost-effectiveness analysis of two strategies for typing unrelated donors for bone marrow transplantation in France.

Large Registries of HLA-typed potential volunteer donors have been set up in numerous countries to find HLA-matched unrelated bone marrow donors. This study compared two strategies medicoeconomically for HLA typing in the context of a bone marrow volunteer donor Registry. It investigated the cost-effectiveness of strategies before and after the French Registry was modified in January 1999: HLA- A, B typing only at registration and secondary HLA-DR typing on part of the Registry (AB strategy) vs. typing at once for HLA- A, B, and DR (ABDR strategy). The point of view considered was that of payers, French typing tariffs with a 5% discount rate were used, effectiveness was defined as identification of at least one donor with no HLA-A, B, DR incompatibilities for a given recipient (compatible potential donor), the observation period was 9 months, and the judgement criterion was the differential cost-effectiveness ratio. The ABDR strategy identified 94.7% (142/150) of compatible potential donors. The differential cost-effectiveness ratio between the two strategies was 387,005 francs (Euro 58,995) for one supplementary compatible potential donor. Compared with a "do nothing" policy, the ratio was 3,744,087 francs (Euro 570,745) for the AB strategy vs. 576,136 francs (Euro 87,826) for the ABDR strategy. The ABDR strategy is thus more effective but also more costly than the AB strategy. Nevertheless, because of its lower effectiveness and the size of available ABDR Registries, the AB strategy will become obsolete.

'BIO-ID': restricted use of HLA markers to detect double registration on computer files.

We propose to use the extreme diversity of HLA in order to detect, by anonymous check, double registration on computer files, of patients waiting for organ transplantation. A simulation on a panel of 69461 unrelated individuals, caucasoid, confirms the relevance of the method.

EMDIS: European Marrow Donor Information System.

EMDIS is an open network between different bone marrow Donor Registries for patients awaiting a transplant and lacking compatible family donors. The network is composed of an identical system in all countries. The architecture makes clear definition between the user system (US) and the EMDIS core system (CS). E-mail approach is used as communication method. A logical model including the EMDIS CS and the US, as well as the list of messages exchanged between US/CS and CS/CS, has been defined. An actually functioning pilot system between three European countries could be used as a trial basis by other research projects.