title: CTLA-4 +49A>G polymorphism of recipients of HLA-matched sibling allogeneic stem cell transplantation is associated with survival and relapse incidence.
abstract: Conflicting observations have been reported about the role of CTLA-4 gene polymorphisms in the clinical outcome of allogeneic hematopoietic stem cell transplantation (HSCT). We have investigated three polymorphisms of the CTLA-4 gene (-318C>T, +49A>G, CT60G>A) in 133 donor/recipient pairs who underwent HLA-matched sibling donor HSCT for hematological malignancies. We found no association of the clinical outcome of the HSCT with either recipient or donor -318C>T and CT60G>A polymorphisms. At variance, we found a significant association of donor +49A>G G/G genotype with longer overall survival (OS; log-rank test, P = 0.04), and the number of +49A>G G-alleles in the recipient with longer OS (P = 0.027), longer disease-free survival (P = 0.036) and reduced relapse rate (P = 0.042). However, only recipient +49A>G polymorphism was retained as independent prognostic factor in a multivariate analysis, suggesting that the expression of CTLA-4 on the cells of recipient may be relevant for the clinical outcome of HSCT.
authors.affiliation: Medical Oncology C, National Cancer Research Institute, Genoa, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Piccioli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Balbi
authors.forename: Martina
authors.initials: M
authors.lastname: Serra
authors.forename: Anna
authors.initials: A
authors.lastname: Morabito
authors.forename: Teresa
authors.initials: T
authors.lastname: Lamparelli
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Stefania
authors.initials: S
authors.lastname: Laurent
authors.forename: Beatrice
authors.initials: B
authors.lastname: Dozin
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ferraris
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: Rosario
authors.initials: R
authors.lastname: Notaro
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Pistillo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D054437:Myelodysplastic-Myeloproliferative Diseases / Q000453:epidemiology / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012008:Recurrence; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human