HLA Matching Considerations for Unrelated Donors If clinicians choose siblings with multiple antigen mismatches as donors, haploidentical approaches may be warranted. Any siblings with single mismatches should have extended typing to ensure that if the mismatch is caused by a crossover, it only occurs with one antigen.
#ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FULL#
Any related donor that is not a full sibling should have full HLA typing because similar haplotypes from different parents could differ at the allele level.Īlthough single-antigen mismatched related donors (5/6 antigen matched) were used interchangeably with matched sibling donors in some studies, a large Center for International Blood and Marrow Transplant Research (CIBMTR) study in pediatric HSCT recipients showed that the use of 5/6 antigen-matched related donors resulted in rates of GVHD and overall survival (OS) equivalent to rates in 8/8-allele-level-matched unrelated donors and slightly inferior survival than in fully matched siblings. Because a crossover event could involve the HLA C antigen and because parents may share HLA antigens that actually differ at the allele level, many centers perform allele-level typing of possible sibling donors at all of the key HLA antigens (HLA A, B, C, and DRB1). Given the distance between HLA A and HLA DRB1 on chromosome 6, there is approximately a 1% possibility of a crossover event occurring in a possible sibling match. The most commonly used related donor is a sibling from the same parents who, at a minimum, is HLA matched for HLA A, HLA B, and HLA DRB1 at the antigen level. HLA Matching Considerations for Sibling and Related Donors Polymorphisms of the HLA proteins outside of these areas are not involved in the function of these molecules therefore, they are often not assessed as part of HLA testing and unlikely to contribute to HLA mismatch. The term for allele-level matching used in their guidelines is antigen recognition domain, which refers to the fact that the allele-level similarities used to define the specific HLA type are associated with areas directly used for antigen recognition.
The National Marrow Donor Program has published guidelines for HLA matching. Because of this, DNA-based allele-level HLA typing is standard when unrelated donors are being chosen. These differences are clinically relevant because the use of donors with allele-level mismatches affects survival and rates of graft-versus-host disease (GVHD) to a degree similar to that in patients with antigen-level mismatches. Full siblings of cancer patients have a 25% chance of being HLA matched.Įarly serologic techniques of HLA assessment defined a number of HLA antigens, but more precise DNA methodologies have shown HLA allele-level mismatches in up to 40% of serologic HLA antigen matches. HLA class I (A, B, C, etc.) and class II (DRB1, DRB3, DRB4, DRB5, DQB1, DPB1, etc.) alleles are highly polymorphic therefore, finding appropriately matched unrelated donors is a challenge for some patients, especially those of certain racial groups (e.g., patients with African, Hispanic, Asian, or Pacific-Islander ancestry). The locations of specific HLA loci for the class I B, C, and A alleles and the class II DP, DQ, and DR alleles are shown.
Human chromosome 6 with amplification of the HLA region.
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