Hlamatched Related Donors

While HLA-identical siblings have inherited the same haplotypes from each parent, other HLA-matched family members may be identified. These may include siblings, parents, and more distantly related individuals. Such individuals have typically inherited one HLA haplotype in common with the patient and a second, matched haplotype of independent origin. Since one haplotype is of independent origin, a higher level of HLA testing is needed to determine the level of similarity of the nonshared haplotype. Both the patient and the prospective donor should be tested for all relevant HLA loci at high resolution. Even when the non-shared haplotype is found to be identical at each tested locus, identity cannot be assumed for untested loci or DNA segments that may be relevant to transplant outcome (e.g., minor histocompatibility antigens, cytokine genes). Thus, donors HLA identical by descent may be preferred to over matched, but haplotype distinct related donors.

An HLA-matched, but haplotype distinct related donor may be favored over a matched unrelated donor on at least three counts. First, the shared haplotype is identical (within the boundaries marked by the tested loci), including any additional genes that may be important to transplant outcome. Second, a related donor is expected to share more minor histocompati-bility genes with the patient than an unrelated donor. Third, a related donor is generally more accessible and may result in a more timely transplant.

When an HLA-identical sibling is not identified in the immediate family, the possibility that a more distant relative might be matched should be considered.78 This may be particularly relevant when the patient has a rare HLA allele or haplotype paired with a haplotype that is frequent in the general population. The probability of finding a more distant matched relative is a function of the number of relatives available and the frequency of the more common haplotype in the general population or the ethnic group of the family. Allele and haplotype frequencies in various populations are available.57'58 65-70 The typical approach is to first determine which branch of the family carries the rare HLA allele or haplotype (e.g., maternal or paternal) and then to trace the rare haplotype by typing additional key relatives.

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