title: Cytomegalovirus-specific immune recovery following allogeneic HLA-identical sibling transplantation with reduced-intensity preparative regimen.
abstract: Cytomegalovirus (CMV) represents a major cause of morbidity after allogeneic stem cell transplantation (allo-SCT). Using interferon-gamma-enzyme-linked immunospot (ELISPOT) assay and HLA-peptide tetramers, we analysed 54 patients who received a reduced-intensity conditioning regimen, including fludarabine, busulphan and antithymocyte globulin (ATG), with the aim of defining essential elements of protective immunity to CMV. The cumulative incidence of CMV positive antigenaemia was 37% occurring at a median of 43 days (range, 7-104) after allo-SCT. In univariate analysis, conditioning regimen (ATG dose) and graft characteristics (graft source and CD3+ T-cell dose) significantly influenced CMV-specific immune recovery. A significant correlation (P=0.000002) was found between CMV-specific T cells detected by IFN-gamma ELISPOT assay and pp65-specific CD8+ T-cell frequency quantified by tetramers. CMV-specific CD8+ T cells presented a phenotype of effector cells (perforin and 2B4 positive). In multivariate analysis, bone marrow (BM) as a graft source was the only variable associated with an increased risk of CMV positive antigenaemia (P=0.0001) in line with the ELISPOT assay showing a higher frequency of functional CMV-specific effectors within peripheral blood stem cell grafts as compared to BM. Thus, early monitoring of CMV-specific immune recovery using sensitive new tools might prove useful for patient management after allo-SCT.
authors.affiliation: Unité de Transplantation et de Thérapie Cellulaire, Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Marseille, France. mohtym@marseilles.fr
authors.forename: M
authors.initials: M
authors.lastname: Mohty
authors.forename: A M
authors.initials: AM
authors.lastname: Mohty
authors.forename: D
authors.initials: D
authors.lastname: Blaise
authors.forename: C
authors.initials: C
authors.lastname: Faucher
authors.forename: K
authors.initials: K
authors.lastname: Bilger
authors.forename: D
authors.initials: D
authors.lastname: Isnardon
authors.forename: D
authors.initials: D
authors.lastname: Sainty
authors.forename: J A
authors.initials: JA
authors.lastname: Gastaut
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.forename: D
authors.initials: D
authors.lastname: Olive
authors.forename: B
authors.initials: B
authors.lastname: Gaugler
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D035781:Siblings; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D000956:Antigens, Viral; D006680:HLA Antigens