Biological and Genetic Aspects of Donor-Recipient Matching in HSCT.

Abstract

Bone marrow transplantation is a routine clinical activity offering salvage therapy in a number of hematological diseases and inborn errors. There are two obstacles that may delay or even postpone this curable treatment approach. The first is a lack of matched family donors, which affects up to 75% of patients. In this situation a search for unrelated donors, if successfully completed, makes this approach feasible. HLA genes of five loci (A, B, C, DR, and DQ) are currently considered as a basis for matching. Each day brings information of new alleles. Genetic typing can lead to detection of diversity at the single nucleotide level. It ensures that a level of matching is achieved resulting in transplant success rates similar to those seen among siblings sharing the same HLA genotype. While we wish to have a perfect match, also important is elapsing time during the search process, which is related to the presence in the patient of rare alleles and unusual B-C, DR-DQ associations. Having a primary typing of a patient we can predict the chance for a proper match. Each day new donors are recruited worldwide. Iterative searching must be applied in the latter situation. In some cases 6 or more potential donors are required to have a donor accepted by a clinician. Finally, a compromise must be reached between the aspiration of matching at the level of 10 alleles and the urgency of transplantation in patients suffering from relapsing disease. To facilitate the decision-making process, modern information technology must be at hand. The search process includes the complete donor pool which is screened for potential donors. The chosen potential donors must be activated for confirmatory typing which includes 5 loci specificities typed at the high resolution level with exchange of information between registries and the hospital iteratively coming to the optimal decision. The process must be reliable, safe, and transparent, and must operate efficiently in real time. The European Marrow Donor Information System (EMDIS), used in many countries worldwide, ensures fulfillment of the above requirements. The present volume illustrates the above points, supporting the rational basis for the decision-making process.