title: High-resolution HLA matching in hematopoietic stem cell transplantation: a retrospective collaborative analysis.
abstract: To validate current donor selection strategies based on previous international studies, we retrospectively analyzed 2646 transplantations performed for hematologic malignancies in 28 German transplant centers. Donors and recipients were high resolution typed for HLA-A, -B, -C, -DRB1, and -DQB1. The highest mortality in overall survival analysis was seen for HLA-A, -B, and DRB1 mismatches. HLA-DQB1 mismatched cases showed a trend toward higher mortality, mostly due to HLA-DQB1 antigen disparities. HLA incompatibilities at >1 locus showed additive detrimental effects. HLA mismatching had no significant effect on relapse incidence and primary graft failure. Graft source had no impact on survival end points, neither in univariate nor in multivariate analysis. Higher patient age, advanced disease, transplantations before 2004, patient C2C2 killer cell immunoglobulin-like receptor (KIR)-ligand phenotype, and unavailability of a national donor adversely influenced outcomes in multivariate analysis. Our study confirms the association of HLA-A, -B, -C, and -DRB1 incompatibilities with adverse outcome in hematopoietic stem cell transplantation (HSCT). The relevance of HLA-DQB1 disparities in single mismatched transplantations remains unclear. Similar hazard ratios for allele and antigen mismatches (possibly with an exception for HLA-DQB1) highlight the importance of allele level typing and matching in HSCT. The number of incompatibilities and their type significantly impact survival.
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg-Hessen, and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fürst
authors.forename: Carlheinz
authors.initials: C
authors.lastname: Müller
authors.forename: Vladan
authors.initials: V
authors.lastname: Vucinic
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herr
authors.forename: Martin
authors.initials: M
authors.lastname: Gramatzki
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: Renate
authors.initials: R
authors.lastname: Arnold
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Gerald
authors.initials: G
authors.lastname: Wulf
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Bertram
authors.initials: B
authors.lastname: Glass
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Joannis
authors.initials: J
authors.lastname: Mytilineos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005858:Germany; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D014019:Tissue Donors; D014181:Transplantation Immunology / Q000276:immunology; D055815:Young Adult
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains