The ECP is based on extracorporeal irradiation of circulating pathogenic T cells (e.g., malignant or autoimmune cells) with UV-A light in the presence of photosensitizing psoralens. It was developed in the late 1970s and early 1980s by Edelson and colleagues at the National Institutes of Health and later Yale University with the primary goal to treat patients with a leukemic form of cutaneous T-cell lymphoma i.e., SS. One rationale for targeting phototherapy to blood cells circulating in SS patients was the fact that PUVA therapy was shown to be successful in the treatment of MF.
To reach the systemically circulating neoplastic cells in SS patients, a device was developed to irradiate blood derived mononuclear cells with UV-A light in the presence of 8-methoxypsoralen (8-MOP) in an extracorporeal photopheresis chamber.
The complete mode of action of ECP is not fully understood. There were early suggestions about a vaccine effect against pathogenic circulating T lymphocytes since only 10% of the circulating lymphocytes are irradiated. A simple destruction of malignant lymphocytes would therefore not explain the effects of ECP. Recent data support the notion that antigen presenting dendritic cells are activated in the photo-pheresis chamber, take up pathogenic T cells such as malignant CTCL cells and present them to the immune system after re-infusion (20). The ECP might be therefore considered as some sort of dendritic cell vaccination (21). Further evidence support the notion that ECP induces TNF alpha which has a wide range of antitumorigenic actions as well as apoptosis in malignant T-cell clones (22).
The main indication of ECP is Sezary Syndrome(SS). In a 1994 consensus conference ECP was proposed to be the first line treatment of this disease (23). Another excellent indication is "Red Man'' syndrome (24). Available data on MF are less convincing. Apart from CTCL, other major indications include solid organ transplantation, graft vs. host reaction and atopic dermatitis.
The current treatment protocol is still based on the originally described procedure (25). Access is obtained via an antecubital vein. During six treatment cycles, red blood cells are separated from white blood cells in a centrifuge. Red blood cells are immediately returned to the patient, while the white blood cells (buffy coat) are collected and circulate extracorporally through the photopheresis chamber. One of the major recent developments is the injection of photosensitizing methoxyp-soralens directly in the photopheresis chamber instead of giving it to the patient before treatment. After a total dose of 2 Joule/cm2 UV-A irradiation, cells are returned to the patient. Therapy is performed on two consecutive days, every 2-4 weeks depending on the treatment protocol.
The first published study on ECP treatment in CTCL patients showed that approximately two-thirds of patients respond to therapy (25). The same was true for those with nodal involvement. In a follow-up study, an increase in survival time compared to historical controls was shown (26). However, a randomized study has not yet been performed.
The modality most often combined with ECP is IFN-alpha 1.5-5 million units, three times per week, increase the effectiveness of ECP (27). Case reports have shown beneficial effects of adding acitretin 25-50 mg per day.
The ECP is a very well tolerated therapy with high patient compliance for the treatment of SS and other indications such as solid organ transplantation. The therapy generally achieves treatment success in about two-thirds of SS patients and should be tried as first line therapy in this otherwise difficult to treat disease.
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