The transplantation of hematopoietic stem cells is a potentially curative therapy for a
variety of hematologic and non-hematologic diseases. HLA matching of donor and recipient
is essential in order to reduce the risk of severe acute graft-versus-host disease (GVHD).
Despite a continuously growing number of potential stem cell donors and cord blood units
it may be impossible to find an HLA-compatible donor for carriers of rare antigens or
unusual haplotypes. Furthermore, the advance of HLA typing at the allelic level
will probably reveal far more subtype mismatches presently not detected. |
When there is no genotypically identical sibling and there are several alternative potential
donors that all have a mismatch at an HLA class I or II locus, the allogenicity of mismatches may
be estimated using the Sequence Similarity Matching concept described by our working group.
In this concept the amino acid differences between HLA alleles are evaluated and rated with
regard to position within the molecule (peptide binding, contact with the T-cell receptor)
and with regard to functional similarity of amino acids within proteins.
This procedure led to a dissimilarity score (allogenicity index)
whereby high values represent high dissimilarity. When there are several mismatched donors,
dissimilarity scores may be calculated for any of them, and the donor with the least may be preferred.