title: Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation.
abstract: The importance of donor-recipient human leukocyte antigen (HLA)-DPB1 matching for the clinical outcome of unrelated hematopoietic stem cell transplantation (HSCT) is controversial. We have previously described an algorithm for nonpermissive HLA-DPB1 disparities involving HLA-DPB1*0901,*1001,*1701,*0301,*1401,*4501, based on T-cell alloreactivity patterns. By revisiting the immunogenicity of HLA-DPB1*02, a modified algorithm was developed and retrospectively tested in 621 unrelated HSCTs facilitated through the Italian Registry for oncohematologic adult patients. The modified algorithm proved to be markedly more predictive of outcome than the original one, with significantly higher Kaplan-Meier probabilities of 2-year survival in permissive compared with nonpermissive transplantations (55% vs 39%, P = .005). This was the result of increased adjusted hazards of nonrelapse mortality (hazard ratio [HR] = 1.74; confidence interval [CI], 1.19-2.53; P = .004) but not of relapse (HR = 1.02; CI, 0.73-1.42; P = .92). The increase in the hazards of overall mortality by nonpermissive HLA-DPB1 disparity was similar in 10 of 10 (HR = 2.12; CI, 1.23-3.64; P = .006) and 9 of 10 allele-matched transplantations (HR = 2.21; CI, 1.28-3.80; P = .004), both in early-stage and in advanced-stage disease. These data call for revisiting current HLA matching strategies for unrelated HSCT, suggesting that searches should be directed up-front toward identification of HLA-DPB1 permissive, 10 of 10 or 9 of 10 matched donors.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, Department of Oncology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Crocchiolo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Zino
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.forename: Rosi
authors.initials: R
authors.lastname: Oneto
authors.forename: Barbara
authors.initials: B
authors.lastname: Bruno
authors.forename: Simona
authors.initials: S
authors.lastname: Pollichieni
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Sacchi
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Jessica
authors.initials: J
authors.lastname: Marcon
authors.forename: Teresa
authors.initials: T
authors.lastname: Lamparelli
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.forename: Lucia
authors.initials: L
authors.lastname: Garbarino
authors.forename: Valeria
authors.initials: V
authors.lastname: Miotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bandini
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: Katharina
authors.initials: K
authors.lastname: Fleischhauer
mesh_terms: D000328:Adult; D000465:Algorithms; D018572:Disease-Free Survival; D046148:Donor Selection / Q000379:methods*; D005260:Female; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains