Cutaneous T-cell lymphoma (CTCL), the most common cutaneous lymphoma, is a broad term including: mycosis fungoides, Sezary syndrome, primary cutaneous anaplastic large-cell lymphoma (ALCL) and other related entities. Cutaneous T-cell lymphoma (CTCL), a malignancy of mature T cells, is usually due to a CD4+ helper T cell subset that is characterized by a predisposition to localize in the skin (epidermotropism). In 1987 Edelson et. al. Reported that extracorporeal photochemotherapy (ECP) or photopheresis was an effective therapeutic modality to treat patients with erythrodermic CTCL. The initial VUMC/NVAMC study of twenty ECP-treated patients with CTCL was reported in 1992 and the long-term follow-up of this cohort showed a 25% complete remission rate. This study will use an existing serum and tissue bank from ECP-treated patients with CTCL and other diseases with activated lymphocytes to retrospectively and then prospectively evaluate parameters that correlate with CTCL severity, transformation and survival/prognosis. Soluble IL-2R (slL- 2R) levels in the serum of patients with malignant lymphoma, including CTCL have been shown to correlate with disease activity and tumor burden. Recent studies have suggested that slL-2R serum concentration provides an objective, highly reproducible measure of tumor burden in patients with CTCL. Using an ELISA sandwich technique, soluble lL- 2 receptor levels will be measured in stored frozen serum samples from CTCL patients treated with ECP at VUMC/NVAMC and obtained during each two-day cycle of ECP since 1988 (more 1000 samples). A study of six ECP-treated patients with CTCL assessed serial slL-2R levels and showed a correlation between slL-2R levels and clinical course. I will test the following hypotheses: 1. Soluble lL-2R levels correlate with disease activity and tumor burden at initiation of ECP. 2. The change in serial slL-2R levels of individuals patients correlates with response or lack of response to ECP. Can serial serum slL-2R levels be used to monitor response to therapy in CTCL patients treated with EPC? 3. The initial slL-2R level can be used to predict response to ECP and correlates with long-term survival. If the initial results are encouraging, subsequent studies will investigate the role of other cytokines (lL-4, lL-5, lL-10, interferon-gamma, TNF) implicated in the pathogenesis of CTCL and their correlation with diseases severity, response to therapy, and survival. Assessment of tumor burden in CTCL by visual estimation of percent body surface area involved in inaccurate and difficult to reproduce. To accurately determine disease activity and tumor burden, clinical photographs already available on several ECP-treated CTCL patients will be digitized using a slide scanner and analyzed using image analysis software to calculate per cent body surface area involved with CTCL. Data will be analyzed statistically to see if slL-2R levels and other laboratory parameters correlate with visual measures of tumor burden on the skin of thee patients. Because there is no software program specifically designed for this clinical application, a preliminary inquiry will investigate two or three image analysis software packages to determine which program will best suit the needs of this study. Because of the paucity of simple, standardized indicators of patient improvement or progression in CTCL, an objective, efficient, and easily reproducible serum marker would be a valuable addition to the future care of these patients. Further, the identification of a reliable, objective software program to calculate per cent body surface area involved with CTCL will have potential clinical research applications in many skin disease including psoriasis, wound healing studies, and the assessment of burn patients.

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