title: HLA Association with hematopoietic stem cell transplantation outcome: the number of mismatches at HLA-A, -B, -C, -DRB1, or -DQB1 is strongly associated with overall survival.
abstract: HLA matching between the donor and recipient improves the success of unrelated hematopoietic stem cell transplantation (HSCT). Because many patients in need of an unrelated transplant have only donors with mismatch, information is needed to evaluate the limits of HLA mismatching. We examined the association of survival, acute graft-versus-host disease (aGVHD) and relapse with HLA-A, -B, -C, -DRB, -DQB1, and -DPB1 mismatching in 334 patients coming from 12 French transplant centers and who received a non-T cell-depleted bone marrow graft from an unrelated donor. All patients were prepared with the use of myeloablative conditioning regimens. Our analyses demonstrate negative effects of HLA mismatching for either HLA-A, -B, -C, -DRB1, or -DQB1 loci on survival. Multivariate Cox analyses showed that a single mismatch was associated with a significant decrement in survival (P=.046, hazard ratio [HR]=1.41, confidence interval [CI] 95% 1.1-1.98). The presence of multiple mismatches was worse for survival (P=.003, HR=1.91, CI 95% 1.26-2.91) and severe aGVHD (grade III-IV) (P=.002, HR=2.51, CI95% 1.41-4.46). The cumulative incidences of aGVHD and relapse in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with 2, 1, or 0 DPB1 incompatibilities were 63%, 50%, and 51%, and 12%, 27%, and 20%, respectively, but these differences were not statistically significant. Similar differences of aGVHD and relapse, but not statistically significant, were observed in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with DPB1 disparities classified into permissive or nonpermissive mismatches according to Zino's classification based on a hierarchy of the immunogenicity of the HLA-DP molecules. "Missing killer cell immunoglobulin-like receptor (KIR) ligand" evaluated on the presence of HLA-C1, -C2, and Bw4 groups in the recipients was not associated with aGVHD, survival, and relapse in this cohort of non-T cell-depleted HSCT.
authors.affiliation: Service d'immunologie et histocompatibilité, hôpital Saint-Louis, AP-HP Paris, France. pascale.loiseau@univ-paris-diderot.fr
authors.forename: Pascale
authors.initials: P
authors.lastname: Loiseau
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Balere
authors.forename: Anne
authors.initials: A
authors.lastname: Dormoy
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Bignon
authors.forename: Katia
authors.initials: K
authors.lastname: Gagne
authors.forename: Lucette
authors.initials: L
authors.lastname: Gebuhrer
authors.forename: Valérie
authors.initials: V
authors.lastname: Dubois
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jollet
authors.forename: Monique
authors.initials: M
authors.lastname: Bois
authors.forename: Pascale
authors.initials: P
authors.lastname: Perrier
authors.forename: Dominique
authors.initials: D
authors.lastname: Masson
authors.forename: Agnès
authors.initials: A
authors.lastname: Moine
authors.forename: Léna
authors.initials: L
authors.lastname: Absi
authors.forename: Denis
authors.initials: D
authors.lastname: Reviron
authors.forename: Virginia
authors.initials: V
authors.lastname: Lepage
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.forename: Evelyne
authors.initials: E
authors.lastname: Marry
authors.forename: Zina
authors.initials: Z
authors.lastname: Chir
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Jouet
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Colette
authors.initials: C
authors.lastname: Raffoux
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006680:HLA Antigens / Q000009:adverse effects / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D006680:HLA Antigens