Haema 2010; 1(1): 85-93
by J. Dervenoulas and P. Tsirigotis
2nd Department of Internal Medicine, General University Hospital “Attikon”, Athens
Abstract
Extracorporeal photopheresis (ECP) is an effective treatment modality for patients with erythrodermic mycosis 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 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 induce apoptosis of normal and neoplastic lymphocytes, while enhances 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 anti-tumor specificity. The efficacy and excellent safety profile of ECP has been showed 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 like 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. 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.