Abstract and Introduction
Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy.
Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions (Figure 1).[1,2] ECP was initially approved by the Food and Drug Administration (FDA) in the United States in 1988 for the treatment of S.zary syndrome (SS), a leukemic form of cutaneous T-cell lymphoma (CTCL) with an aggressive clinical course, characterized by a triad of circulating neoplastic T-cells, erythroderma, and lymphadenopathy. Although CTCL remains the only FDA-approved indication, ECP has since been used as an off-label treatment for numerous other conditions, including graft-versus-host (GvHD) disease, systemic sclerosis (SSc), autoimmune bullous dermatoses, Crohn's disease, and to prevent solid organ transplant rejection.[1,2] In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis (Table 1 and Table 2). The goal of this article is to review the current concepts regarding ECP mechanism of action, treatment considerations as well as suggested treatment protocols and efficacy in CTCL, GvHD, systemic sclerosis and other skin diseases.
Mechanism of action of ECP. Figure adapted from Comprehensive Dermatologic Drug Therapy by Wolverton SE.1
ECP involves placing a catheter to gain access to the venous circulation and collecting blood via continuous or discontinuous cycles, which is then centrifuged to create a leukocyte-rich buffy coat. The isolated leukocytes are then placed in a sterile treatment cassette, injected with liquid 8-methoxypsoralen (8-MOP) and exposed to ultraviolet A (UVA) radiation. Afterwards, the photochemically-altered white blood cells are returned to the patient's venous circulation (Figure 1).[1,2] The Therakos® ECP machine (the only available unit for this treatment) represents an automated closed system. Each treatment lasts approximately 1.5–3 hours, and the scheduling and frequency of treatments depend on the disease being treated.
The exact mechanism of action of ECP remains unknown, however, in CTCL, it is believed that the procedure leads to DNA-crosslinking and apoptosis of pathogenic T cells induced by 8-MOP with UVA exposure, the differentiation of monocytes to dendritic cell that present tumor antigens from apoptotic lymphocytes, stimulation of anti-tumor immune responses, and shifting of immunoregulatory cytokines to Th1 cytokine profile, such as interferon-gamma and tumor necrosis factor (TNF) alpha, thus restoring the Th1/Th2 balance.[1–4] In particular, ECP targets mostly tumor cells since the absolute number of normal T cells remains relatively stable after the procedure. Given its therapeutic benefit in transplant rejection and autoimmune diseases, ECP is also believed to have unique immunomodulatory properties generating needed responses in an autoimmune setting, which are thought to be similarly mediated by DNA-crosslinking and apoptosis of autoreactive leucocytes (natural killer (NK) and T cells) and induction of T-regulatory cells after treatment, although this phenomenon was not observed in patients with SS. However, unlike immunosuppressive therapies, ECP is not associated with an increased risk of opportunistic infections. In fact, ECP is overall well-tolerated, with no reports of post-treatment Grade III or IV side effects, as per the World Health Organization classification. In particular, ECP is not associated with side-effects that are observed with skin systemic psoralen with UVA (PUVA) therapy, since the psoralen is not ingested orally nor applied to the skin. The side-effects are primarily related to fluid shifts and the need for a central catheter. Rare side-effects of ECP include nausea, photosensitivity, transient hypotension, flushing, tachycardia, congestive heart failure and thrombocytopenia.[1,2] Contraindications to the use of ECP are summarized in Table 3. Currently, ECP is available in over 200 treatment centers across the world treating numerous diseases. The use of ECP by hospital, region and indication in Canada is summarized in Table 1 and Table 2. Unfortunately, treatment access is limited in Canada and significant knowledge gaps are recognized (i.e., paucity of randomized clinical trials and real-world evidence) amongst physicians and patients. As a result, this treatment may be significantly underused in Canada.
Skin Therapy Letter. 2022;27(5):1-6. © 2022 SkinCareGuide.com