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Ann Hematol (2010) 89:613618 DOI 10.1007/s00277-009-0885-5
ORIGINAL ARTICLE
CTLA-4 +49A>G polymorphism of recipientsof HLA-matched sibling allogeneic stem cell transplantation is associated with survival and relapse incidence
Patrizia Piccioli & Giuseppe Balbi & Martina Serra & Anna Morabito &
Teresa Lamparelli & Marco Gobbi & Stefania Laurent & Beatrice Dozin & Paolo Bruzzi &
Anna Maria Ferraris & Andrea Bacigalupo & Rosario Notaro & Maria Pia Pistillo
Received: 19 February 2009 /Accepted: 4 December 2009 /Published online: 18 December 2009 # Springer-Verlag 2009
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.
Keywords CTLA-4 polymorphism . Transplant outcome . Survival . Disease relapse
Introduction
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T cell activation [1, 2] which, as suggested by studies in animal models of transplant [3-5], may contribute to modulate immune response and tolerance in both solid organ and hematopoietic stem cell transplantation (HSCT).
Rosario Notaro and Maria Pia Pistillo equally contributed to this work.
P. Piccioli : M. SerraMedical Oncology C, National Cancer Research Institute, Genoa, Italy
G. BalbiDepartment of Oncology, Biology and Genetics, University of Genoa,Genoa, Italy
A. Morabito : S. Laurent : M. P. Pistillo (*)
Breast Cancer Laboratory of Tumour Genetics Unit, National Cancer Research Institute,L.go R. Benzi 10,16132 Genoa, Italye-mail: [email protected]
T. Lamparelli : A. BacigalupoDivision of Hematology, San Martino Hospital, Genoa, Italy
M. GobbiDepartment of Hematology and Oncology, University of Genoa, Genoa, Italy
B. Dozin : P. BruzziClinical Epidemiology...