The role of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphomas.

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Address: 2nd Department of Internal Medicine, ATTIKON General University Hospital, Medical School, University of Athens, Greece. atta_maria@yahoo.com
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abstract

extracorporeal photochemotherapy (ECP) is an effective treatment modality for patients with erythrodermic myocosis fungoides (MF) and Sezary syndrome (SS). During ECP, a fraction of peripheral blood mononuclear cells is collected, incubated ex-vivo with methoxypsoralen, UVA irradiated, and finally reinfused to the patient. Although the mechanism of action of ECP is not well established, clinical and laboratory observations support the hypothesis of a vaccination-like effect. ECP induces apoptosis of normal and neoplastic lymphocytes, while enhancing differentiation of monocytes towards immature dendritic cells (imDCs), followed by engulfment of apoptotic bodies. After reinfusion, imDCs undergo maturation and antigenic peptides from the neoplastic cells are expressed on the surface of DCs. Mature DCs travel to lymph nodes and activate cytotoxic T-cell clones with specificity against tumor antigens. Disease control is mediated through cytotoxic T-lymphocytes with tumor specificity. The efficacy and excellent safety profile of ECP has been shown in a large number of retrospective trials. Previous studies showed that monotherapy with ECP produces an overall response rate of approximately 60%, while clinical data support that ECP is much more effective when combined with other immune modulating agents such as interferons or retinoids, or when used as consolidation treatment after total skin electron beam irradiation. However, only a proportion of patients actually respond to ECP and parameters predictive of response need to be discovered. A patient with a high probability of response to ECP must fulfill all of the following criteria: (1) SS or erythrodermic MF, (2) presence of neoplastic cells in peripheral blood, and (3) early disease onset. Despite the fact that ECP has been established as a standard treatment modality, no prospective randomized study has been conducted so far, to the authors' knowledge. Considering the high cost of the procedure, the role of ECP in the treatment of SS/MF needs to be clarified via well designed multicenter prospective randomized trials.

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