Extracorporeal photopheresis (ECP) was hailed as a new therapeutic concept for the treatment of diseases caused by aberrant T lymphocytes since it was first described more than twenty years ago. Advances in molecular biology and immunology have allowed a greater understanding of the mechanisms involved in ECP. As a result, ECP is being increasingly considered as a safe and promising immunomodulatory therapy with diverse clinical applications. At present ECP is approved by the FDA for the treatment of cutaneous T-cell lymphoma (CTCL). ECP is considered a relatively safe and promising immunomodulatory therapy with diverse clinical applications reported in the literature. ECP has been used in the treatment of patients following acute allograft rejection in cardiac, lung, renal or liver transplantation, graft-versus-host disease, systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis and pemphigus vulgaris. The use of ECP as a novel form of therapy is in constant evolution with newer studies focusing on the treatment of patients with Crohn's disease and the immunological effects of ECP in children with type 1 diabetes mellitus. However, because the exact mechanism by which ECP exerts its effects remains to be described in detail and because important questions regarding the use of ECP in the clinical setting, such as length of therapy or design of specific protocols, concomitant use of immunosupressive therapy, patient characteristics, long term side effects, assessment of therapy efficacy and cost effectiveness continue to remain unanswered, the exact role of ECP cannot be fully established except in the case of patients with CTCL and GvHD. Nevertheless, future clinical studies with ECP can be done with the objective of designing more appropriate treatment protocols based on expected patient response and with a side effect profile that is fairly tolerable.

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