You are in: eMedicine Specialties > Dermatology > TECHNOLOGY AND DERMATOLOGY Extracorporeal PhotopheresisArticle Last Updated: Mar 8, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Camille E Introcaso, MD, Fellow in Cutaneous Oncology, Department of Dermatology, Hospital of the University of Pennsylvania Camille E Introcaso is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology Coauthor(s): Alain Rook, MD, Professor, Department of Dermatology, University of Pennsylvania Hospital; Michael S Lehrer, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania; Ellen Kim, MD, Assistant Professor, Department of Dermatology, Hospital of the University of Pennsylvania School of Medicine Editors: Harold S Rabinovitz, MD, Clinical Professor, Department of Dermatology, University of Miami School of Medicine; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Amanda Oakley, MBChB, FRACP, Clinical Director, Clinical Associate Professor, Department of Dermatology, Waikato Hospital, Hamilton, New Zealand; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System Author and Editor Disclosure Synonyms and related keywords: ECP, extracorporeal photochemotherapy, leukapheresis, immunomodulatory therapy, cutaneous T-cell lymphoma, CTCL, cutaneous lymphoma, graft versus host disease, solid organ transplant rejection, transplant rejection, graft-vs-host disease, graft-versus-host disease, GVHD, systemic sclerosis, rheumatoid arthritis, Sézary syndrome, Sezary syndrome INTRODUCTIONSection 2 of 10
  Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory therapy that has been approved by the US Food and Drug Administration for the treatment of cutaneous T-cell lymphoma (CTCL) since 1988. ECP, also known as extracorporeal photochemotherapy, is performed at more than 150 centers worldwide for multiple indications. Long-term follow-up data are available from many investigators that indicate ECP produces disease remission and improved survival for CTCL patients. In addition to CTCL, ECP has been shown to have efficacy in the treatment of other T-cell mediated disorders, including chronic graft versus host disease (GVHD) and solid organ transplant rejection. ECP use for the treatment of autoimmune disease, such as systemic sclerosis and rheumatoid arthritis, is also being explored. PROCEDURESection 3 of 10
ECP is performed using the UVAR XTS Photopheresis System developed by Therakos, Inc (Exton, Pa). The process is performed through one intravenous access port and has 3 basic stages: (1) leukapheresis, (2) photoactivation, and (3) reinfusion. The process takes 3-4 hours to complete.
MECHANISM OF ACTIONSection 4 of 10
Over the past 20 years, on-going research has explored the mechanism of action of ECP. The combination of 8-MOP and UVA radiation causes apoptosis of the treated T cells and may cause preferential apoptosis of activated or abnormal T cells, thus targeting the pathogenic cells of CTCL or GVHD. However, given that only a small percentage of the body's lymphocytes are treated, this seems unlikely to be the only mechanism of action. Other evidence suggests that ECP also induces monocytes to differentiate into dendritic cells capable of phagocytosing and processing the apoptotic T-cell antigens. When these activated dendritic cells are reinfused into the systemic circulation, they may cause a systemic cytotoxic CD8+ T-lymphocyte–mediated immune response to the processed apoptotic T-cell antigens. Finally, evidence from animal models also indicates that photopheresis may induce antigen-specific regulatory T cells, which may lead to suppression of allograft rejection or GVHD. ADVERSE REACTIONSSection 5 of 10
ECP is a very well-tolerated procedure. Transient hypotension may occur in some patients during the collection phase of the treatment, but this is asymptomatic in most and usually resolves with reinfusion of the blood products. Occasionally, saline must be given during ECP to maintain blood pressure, and patients taking antihypertensives are asked to withhold these medications until after the procedure. Two to 12 hours after ECP, some patients experience low-grade fevers, likely due to the release of cytokines. Over the same time course, some patients with CTCL may experience an increase in pruritus or redness. Finally, although patients with hypertriglyceridemia do not experience any further adverse events during ECP, they may have a less efficacious treatment because of the inability of the UVAR machine to separate the WBCs from the lipid-rich blood. Because of this, patients should have triglyceride levels of less than 300 mg/dL and should fast (except for fluid intake) before the procedure. In all of the various patient groups treated, no immunosuppression, opportunistic infections, or neoplasia has been associated with ECP. Although 8-MOP is rapidly cleared from the blood, levels in the eyes have not been measured. The risk of cataract formation is minimal if the patient protects the eyes using UVA-blocking sunglasses the day of the procedure. INDICATION - CUTANEOUS T-CELL LYMPHOMASection 6 of 10
CTCL is the name for a group of lymphoproliferative disorders caused by clonally derived, skin-homing, malignant T cells. The most common of these disorders is mycosis fungoides and its leukemic variant, Sézary syndrome, which has peripheral blood, lymph node, and, sometimes, organ involvement. A variety of skin-directed treatments exist for CTCL, which have little effect on the extracutaneous disease of Sézary syndrome. The initial indication for ECP was based on the results of a trial performed with a cohort of 37 CTCL patients in whom 73% had some improvement in skin and/or extracutaneous disease with ECP alone. Since that time, multiple retrospective and prospective studies have indicated that when ECP is used as a single agent, most often with treatments given on 2 consecutive days every 3-4 weeks, overall response rates are 50-80% and complete response rates are 10-25%. More recently, ECP has been used in combination with other immunomodulatory therapies, such as interferons alpha and gamma or oral retinoids, to achieve even higher response rates. In addition to the improvement in cutaneous manifestations of CTCL, ECP has been demonstrated to cause a decrease in the burden of peripheral blood disease and lymphadenopathy. A clinical profile of patients who are more likely to respond to ECP has been developed over the past 20 years of experience. The presence of circulating Sézary cells, identified by abnormal flow cytometry results or histology findings, appears to be necessary for a response. Normal or near-normal numbers of CD8+ cytotoxic lymphocytes, indicating an adequate cell-mediated immunity, also makes a response more likely. Therefore, patients who have had the disease for 2 years or less and who have not undergone systemic cytotoxic chemotherapy are more likely to gain benefit from ECP compared with patients with prolonged disease or those who have been heavily pretreated. INDICATION - ALLOGRAFT REJECTIONSection 7 of 10
Well-supported evidence indicates that ECP is effective for treating acute and chronic cardiac rejection, and studies have suggested that ECP may be beneficial for treating lung, liver, and renal transplant rejection, as well as for preventing episodes of acute rejection. According to the authors' experience, acute or symptomatic rejection should be treated aggressively, with treatments on 2 consecutive days, weekly for the first 2 weeks, and then on alternating weeks until rejection has resolved. Although ECP treatment immediately following lymphocytolytic therapy may be less effective, immunosuppression should be continued. INDICATION - GRAFT-VERSUS-HOST-DISEASESection 8 of 10
GVHD complicates the course of many patients after undergoing allogeneic stem cell transplantation and limits the use of this potentially life-saving therapy. It affects various organ systems and is conventionally divided into acute and chronic GVHD, depending on whether it occurs within the first 100 days posttransplant or beyond that time. ECP has been used for the treatment of immunosuppressive-resistant chronic GVHD for at least 12 years and has been shown to improve skin manifestations, joint mobility, xerostomia, and xerophthalmia. ECP may also improve liver enzyme abnormalities and diarrhea associated with gastrointestinal GVHD, and further studies are currently being conducted to determine the effect of ECP on bronchiolitis obliterans observed in association with GVHD. Studies are also currently underway exploring conditioning with ECP prior to allogeneic stem cell transplantation for preventing GVHD. INDICATION- AUTOIMMUNE DISEASESection 9 of 10
ECP has also been explored as therapy for a variety of autoimmune diseases, including systemic sclerosis. In a study of 79 patients with severe skin involvement, significant improvement of skin softening was demonstrated with ECP compared with D-penicillamine. In a randomized, double-blinded, placebo-controlled trial of 64 patients (ECP vs sham ECP), ECP again had some clinical effects, but statistical significance was not achieved because of the small number of subjects. Similar studies have been performed and suggest efficacy of ECP treatment in type 1 diabetes mellitus, pemphigus vulgaris, epidermolysis bullosa acquisita, atopic dermatitis, and inflammatory bowel disease. Several case series suggest the potential efficacy of ECP for systemic lupus erythematosus and scleromyxedema. Recent reports also suggest the potential efficacy for nephrogenic fibrosing dermopathy/nephrogenic systemic sclerosis. Other possible clinical indications studied in which ECP has not shown benefit include multiple sclerosis, chronic hepatitis C, and psoriasis. REFERENCESSection 10 of 10
Extracorporeal Photopheresis excerpt Article Last Updated: Mar 8, 2007 |
