title: HLAMatchmaker-defined triplet matching is not associated with better survival rates of patients with class I HLA allele mismatched hematopoietic cell transplants from unrelated donors.
abstract: This report addresses the concept that permissible HLA mismatching, that is, mismatches that do not generate an allogeneic response, in hematopoietic stem cell transplantation (HCT) can be determined with structural similarity of polymorphic regions. We have applied the triplet version of a structural algorithm called HLAMatchmaker, which considers short sequences involving polymorphic amino acid residues on the molecular surface as key elements of immunogenic epitopes. The triplet matching effect was analyzed in a National Marrow Donor Program dataset consisting of 744 unrelated hematopoietic cell transplantation cases with 1 HLA-A, -B, or -C mismatch and 1690 fully HLA-A, -B, -C, -DR, or -DQ allele matched cases. In multivariate models adjusting for other significant clinical risk factors, the degree of triplet mismatching did not significantly correlate with patient survival, engraftment, or acute graft-versus-host disease (aGVHD). Other structurally based strategies should be pursued to identify permissible HLA mismatches in HCT.
authors: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: Duquesnoyr@upmc.edu.
authors: Rene
authors: R
authors: Duquesnoy
authors: National Marrow Donor Program, Minneapolis, Minnesota.
authors: Stephen
authors: S
authors: Spellman
authors: Center for International Blood & Marrow Transplant Research, Minneapolis, Minnesota.
authors: Michael
authors: M
authors: Haagenson
authors: Center for International Blood & Marrow Transplant Research, Milwaukee, Wisconsin.
authors: Tao
authors: T
authors: Wang
authors: Center for International Blood & Marrow Transplant Research, Milwaukee, Wisconsin.
authors: Mary M
authors: MM
authors: Horowitz
authors: Leiden University Medical Center, Leiden, The Netherlands.
authors: Machteld
authors: M
authors: Oudshoorn
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D018572:Disease-Free Survival; D046148:Donor Selection / Q000379:methods*; D000939:Epitopes; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy; D015395:Histocompatibility Antigens Class I; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I