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: L E French, T Alcindor, M Shapiro, K S McGinnis, D J Margolis, D Porter, D G B Leonard, A H Rook, F Foss
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 30 Issue 8 Pg. 509-15 (Oct 2002) ISSN: 0268-3369 [Print] England
• PMID: 12379890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers

Topics

• Adult
• Biomarkers
• Blood Cells
• Case-Control Studies
• Chronic Disease
• Clone Cells
• Female
• Gene Rearrangement
• Genes, T-Cell Receptor gamma
• Graft vs Host Disease (immunology, therapy)
• Hematologic Neoplasms (complications)
• Humans
• Male
• Middle Aged
• Photopheresis
• Prognosis
• Skin Diseases (etiology, therapy)
• T-Lymphocytes (cytology)