title: Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease: positive correlation with response to photopheresis.
abstract: Chronic graft-versus-host disease (cGVHD) is a multiorgan disorder with skin manifestations resembling scleroderma. Since photopheresis, a treatment that induces an anticlonotypic immune response, has proven to be effective in both cutaneous T cell lymphomas with circulating clonal T cells and in cGVHD, we have searched for circulating clonal T cell populations in patients with cGVHD, and determined whether T cell clonality in the blood is associated with therapeutic response. We screened blood samples from 27 patients after HLA-matched allogeneic bone marrow transplantation (allo-BMT), 10 without cGVHD and 17 with extensive cGVHD, for clonal T cell receptor gamma (TCR gamma) gene rearrangements using fluorescent-based polymerase chain reaction (PCR) and automated high-resolution capillary electrophoresis. Amplified populations of clonal T cells with unique TCR gamma gene rearrangements were found in six of 10 (60%) allo-BMT patients without cGVHD and 13 of 17 (76.5%) allo-BMT patients with cGVHD (P = 0.41), as compared to none of 10 (0%) healthy controls. Twelve patients with cGVHD were treated by photopheresis, and the presence of amplified populations of clonal T cells was found to be associated with a cutaneous response to photopheresis, as eight of eight (100%) clone-positive vs none of four (0%) clone-negative patients experienced a clinically significant cutaneous response to treatment (P = 0.001). Our findings suggest that patients with cGVHD that have detectable expanded clonal T cell populations in their peripheral blood, may be more likely to respond to treatment by photopheresis.
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: French
authors.forename: T
authors.initials: T
authors.lastname: Alcindor
authors.forename: M
authors.initials: M
authors.lastname: Shapiro
authors.forename: K S
authors.initials: KS
authors.lastname: McGinnis
authors.forename: D J
authors.initials: DJ
authors.lastname: Margolis
authors.forename: D
authors.initials: D
authors.lastname: Porter
authors.forename: D G B
authors.initials: DG
authors.lastname: Leonard
authors.forename: A H
authors.initials: AH
authors.lastname: Rook
authors.forename: F
authors.initials: F
authors.lastname: Foss
mesh_terms: D000328:Adult; D015415:Biomarkers; D001773:Blood Cells; D016022:Case-Control Studies; D002908:Chronic Disease; D002999:Clone Cells; D005260:Female; D015321:Gene Rearrangement; D019675:Genes, T-Cell Receptor gamma; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D017893:Photopheresis; D011379:Prognosis; D012871:Skin Diseases / Q000209:etiology / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D015415:Biomarkers