CTLA-4 +49A>G polymorphism of recipients of HLA-matched sibling allogeneic stem cell transplantation is associated with survival and relapse incidence.
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.
Piccioli
Patrizia
P
Medical Oncology C, National Cancer Research Institute, Genoa, Italy.
Balbi
Giuseppe
G
Serra
Martina
M
Morabito
Anna
A
Lamparelli
Teresa
T
Gobbi
Marco
M
Laurent
Stefania
S
Dozin
Beatrice
B
Bruzzi
Paolo
P
Ferraris
Anna Maria
AM
Bacigalupo
Andrea
A
Notaro
Rosario
R
Pistillo
Maria Pia
MP
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
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human