Extracorporeal photopheresis

PUVA is most useful for the treatment of severe psoriasis. Early (patch and plaque) stage cutaneous T-cell lymphoma (CTCL) also responds to PUVA therapy. In addition, patients in advanced stages of CTCL have been treated with a modification of PUVA known as extracorporeal photopheresis. In this therapy, blood from a CTCL patient who has taken psoralen is exposed to UVA light and returned to the patient. Lymphocytes are altered or destroyed by the treatment, and theoretically, the return of these abnormal cells triggers an immune response directed against certain lymphocyte surface antigens. The effectiveness of this modality appears to be variable. 

Gilliet M, Cozzio A, Burg G, Nestle EO Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis. Br J Dermatol 152 531 -536, 2005. 

Extracorporeal photopheresis (ECP) is a form of pher-esis therapy that has proven effective in the treatment of cutaneous T-cell lymphoma. After oral administration of methoxsalen, leukocytes are separated from whole blood using an ECP device and then exposed to UVA radiation. The irradiated cells then are returned to the patient. Multiple mechanisms probably contribute to the effectiveness of this procedure. ECP simultaneously and efficiently induces apoptosis of disease-causing T-cells and conversion of monocytes to functional dendritic cells by processing and presenting the unique antigenic determinants of pathogenic T-cell clones, the dendritic cells either initiate a clinically relevant anticutaneous T-cell lymphoma cytotoxic response or suppress the activity of autoreactive T-cell clones. 

A high-dose intravenous steroid pulse is the standard treatment for uncomplicated acute rejection. A switch from CsA to Tac is the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or extracorporeal photopheresis. 

Furthermore, psoralens can be employed using a technique called extracorporeal photopheresis (ECP). This modality is a cell-based immunomodulatory therapy involving the separation of leukocyte-rich plasma from patient followed by ex vivo administration of a psoralen and UVA radiation before reinfusion [106]. ECP was first reported in 1987 by Edelson et al., who used it in a clinical trial for the treatment of cutaneous T-cell lymphoma [107], and actually is being increasingly considered as a safe and promising immunomodulatory therapy with multiple and diverse clinical applications. 

TABLE 5 Use of Extracorporeal Photopheresis for Prevention or Treatment of Acute Rejection Episodes after Solid Organ Transplantations ... 

TABLE 6 Extracorporeal Photopheresis Studies Performed in Acute Graft Versus Host Disease Patients with... 

GoUnick, H.P., Owsianowski, M., Taube, K.M., and Orfanos, C.E., Unresponsive and severe generalized pemphigo vulgaris successfully controlled by extracorporeal photopheresis, /. Acad. Dermatol, 28,122,1993. 

Prinz, B., Nachbar, R, and Plewig, G., Treatment of severe atopic dermatitis with extracorporeal photopheresis, Arcfc. Dermatol Res., 287, 48,1994. 

Bisaccia, E., Berger, C., Di Spaltro, R, and Klainer, A.S., Extracorporeal photopheresis in the treatment of AIDS-related complex extended trial, /. Acquir. Immune Defic. Syndr., 6,386, 1993. 

In the oxygen-independent Type III reactions the excited/sensi-tized psoralen donates its excitation energy directly to, or reacts with, the target compound. This occurs if the substrate and the target compound (e.g., DNA) are already in close proximity or intercalated. The reactions will proceed very rapidly via the excited singlet state, and are, typically, cyclization reactions or electron-transfer between the sensitizer and the target. In addition, the psoralen can be ionized, either directly or via the excited state, and react with the target compound in the form of a radical cation. Furocoumarins are also employed in treatment of cutaneous T-cell lymphoma and some infections connected with AIDS, by so-called photopheresis processes [71, 74-76]. In this case, peripheral blood is exposed to, e.g., photoactivated (sensitized) 8-methoxypsoralen (8-MOP) in an extracorporeal flow system. This... 

CTCL Extracorporeal Inject 200 meg into the photoactivation bag during collection cycle using the UVAR photopheresis system, 2 consecutive days every 4 wk for a minimum of 7 treatment cycles. 

In 1982, an extracorporeal form of 8-MOP photochemotherapy (photopheresis) was developed by Edelson et al. for the treatment of cutaneous T-cell lymphoma, a CD4-positive T-cell malignancy. Photopheresis was also found to be effective in a number of other T-cell-mediated diseases. Clinical trials demonstrated beneficial effects in pemphigo vulgaris, severe atopic dermatitis, AIDS-related complex, rheumatoid arthritis, and systemic lupus erythematosus. ... 

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