136: Optimatch® – Optimized Selection of Allele Matched Unrelated Donors from a Large Database
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION(2008)
Abstract
The standard for unrelated donor selection is defined by allele level matching for, at least, HLA-A, -B and -DRB1 with a strong tendency to also include HLA-C and/or -DQB1. Even for patients where such donors will likely exist, the search is hampered by the high prevalence of donors where some of these loci are only typed at intermediate or low resolution, by serology or not at all. A large registry like ZKRD with over 3 million donors can have lists of hundreds or even thousands of similar donor candidates for a substantial fraction of the patients making an efficient search strategy difficult. ZKRD's new OptiMatch® system addresses the issues raised by a three layer concept: (1) The DNA-based search engine uses serology-to-DNA mapping for the identification of donor candidates. The degree of matching can be determined using combinatorial or biostatistical methods. Moreover, the probability of allele level matching of each candidate can not only be determined for each locus based on the allele frequencies of the German population but also much more reliably based on allele resolution haplotype frequencies for HLA-A-B-DRB1, HLA-C-B and HLA-DRB1-DQB1. (2) The web-based front end allows extensive configuration of the way match lists are filtered and sorted, for example: Primary matching can be based on the probability of matching 6/6, 8/8 (including C or DQB1) or 10/10 (including both) alleles, and then the probability of 1 or, finally, 2 allele mismatches. Filters can be applied for gender, CMV status and loci already typed. (3) The sophisticated security architecture is based on strong authentication of users and encrypted data transmission. The new OptiMatch® search engine has been in use since late 2006. Its ability to identify some very likely matching donors among myriads of multiple allele codes gives a stunning power to professional search coordinators. Even in most difficult cases it is apparent upfront which degree of matching can possibly be sought for, which donors should be considered first and which time frame and cost volume should be expected. During its ongoing test phase, the web-based front end is only available in ZKRD's intranet but will be released to outside beta testers before the end of 2007.
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Thymic Selection
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