title: High-resolution HLA matching in unrelated donor transplantation in Switzerland: differential impact of class I and class II mismatches may reflect selection of nonimmunogenic or weakly immunogenic DRB1/DQB1 disparities.
abstract: Unrelated donor searches in Switzerland require high-resolution HLA typing for HLA-A/B/C/DRB1/DRB3,4/DQB1 loci. We evaluated this strategy accepting donors with ⩾9/10 match. Of 802 unrelated donor transplants in 2000-2013, 570 were 10/10 matched, 31 were DRB3/4 mismatched, 261 were single-allele mismatched and 13 had 2 allele mismatches. Of the 261 single-allele disparities, 60 concerned HLA-A/-B, 55 HLA-C and 73 HLA-DRB1/-DQB1 loci. Transplants were reduced intensity conditioning (289, 36%), marrow (187, 23%), EBMT risk score was low in 39, intermediate I in 331, intermediate II in 333 and high in 99 patients. Five-year survival was 48±4%. HLA affected survival in the multivariate model adjusted for risk score. HLA-A/-B and HLA-C mismatches had twice the mortality risks, whereas HLA-DRB1/-DQB1 mismatches were similar to matched transplants. HLA-DRB3/4 mismatches were associated with a nonsignificant increased mortality risk. HLA-DRB3/4 mismatches had higher graft-versus-host disease and transplant-related mortality risks and lower relapse rates compared with matched transplants. We show significant effects of HLA class I, but not HLA class II, mismatches. The lack of impact of DRB1 disparities may be related to the lower immunogenicity of the DRB1*11:01/11:04 and DRB1*14:01/14:54 mismatches, representing 46% of DRB1 incompatibilities. These results support a matching algorithm that prioritizes mismatches considered as more permissive.
authors.affiliation: Division of Hematology, University Hospital Basel, Basel, Switzerland.
authors.forename: J R
authors.initials: JR
authors.lastname: Passweg
authors.affiliation: Division of Hematology, University Hospital, Zürich, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Schanz
authors.affiliation: Service d'Hématologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Chalandon
authors.affiliation: Division of Immunology, University Children's Hospital, Zürich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Güngör
authors.affiliation: SBST Data Office, University Hospital Basel, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Baldomero
authors.affiliation: Division of Hematology, University Hospital Basel, Basel, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Heim
authors.affiliation: Division of Hematology, University Hospital, Zürich, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Nair
authors.affiliation: Division of Hematology, University Hospital Basel, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Medinger
authors.affiliation: Service d'Hématologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Masouridi-Levrat
authors.affiliation: Donor Registry, Swiss Transfusion SRC, Bern, Switzerland.
authors.forename: G N
authors.initials: GN
authors.lastname: de Faveri
authors.affiliation: National Reference Laboratory for Histocompatibility (LNRH), Hôpitaux Universitaires de Genève, Geneva, Switzerland.
authors.forename: J-M
authors.initials: JM
authors.lastname: Tiercy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D046148:Donor Selection; D005260:Female; D059866:HLA-DQ beta-Chains / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate; D013557:Switzerland; D061349:Unrelated Donors
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I