Review
Extracorporeal photopheresis: Past, present, and future

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Extracorporeal photopheresis (ECP) is a leukapheresis-based therapy that uses 8-methoxypsoralen and ultraviolet A irradiation. Used alone or in combination with biological agents, ECP is an established and effective therapy for advanced cutaneous T-cell lymphoma. ECP has also shown promising efficacy in a number of other severe and difficult-to-treat conditions, including systemic sclerosis, graft-versus-host disease, prevention and treatment of rejection in solid organ transplantation, and Crohn disease. Furthermore, the use of ECP in some of these conditions may allow a significant reduction in the use of systemic steroids and other immunosuppressants, reducing long-term morbidity and mortality. The accumulated experience shows ECP to be well tolerated, with no clinically significant side effects. Progress is also being made in the search for understanding of the mechanisms of action of ECP, which will ultimately facilitate improvements in the use of this therapy.

Section snippets

The development of ECP in CTCL

CTCL describes a heterogeneous group of rare lymphoproliferative disorders that are characterized by the accumulation of malignant T-cell clones that home to the skin. The most common form of the disease is mycosis fungoides (MF), which accounts for approximately 60% of new cases. Treatment in the early stages usually involves skin-directed therapies, systemic therapies being used if the disease progresses or for those who present with more advanced-stage MF.1 In the rarer manifestation of

A recommended therapy in CTCL

ECP is now a well-established therapy for CTCL. The original study of ECP in patients with treatment-resistant CTCL reported a response in 27 of 37 patients, showing an average of 64% reduction in cutaneous involvement.3 Since then, numerous studies have been conducted (see review by Knobler and Jantschitsch5). A meta-analysis of 19 studies in patients at all stages of CTCL reported a combined overall response rate of 55.5% with ECP used as monotherapy and 55.7% when used in combination with

ECP may improve skin involvement in systemic sclerosis

Systemic sclerosis is an autoimmune disorder characterized by abnormal deposition of collagen and obliterative vasculopathy in the skin and visceral organs, such as the kidneys, heart, lungs, and gastrointestinal tract. In its severe, progressive form, systemic sclerosis is associated with a pronounced increase in mortality and, as it is an uncommon and heterogeneous condition, few treatments have been tested systematically.

Small pilot studies indicated that ECP had beneficial clinical effects

ECP in the treatment of nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis

Nephrogenic fibrosing dermopathy, a recently described entity that is also called nephrogenic systemic fibrosis, occurs in patients with renal insufficiency. It is associated with fibrosis of the skin and internal organs, and has some characteristics reminiscent of systemic sclerosis, scleromyxedema, and eosinophilic fasciitis.26, 27 Exposure to gadolinium, a contrast agent used in imaging, seems to be closely associated with triggering the disease.28 Effective treatment remains a challenge,

ECP is highly effective in GVHD

GVHD is a serious and frequent complication of allogeneic hematopoietic stem cell transplantation, and contributes substantially to posttransplantation morbidity and mortality. Established first-line therapy consists of corticosteroids, and nonresponding patients require additional immunosuppressive therapies that may impair immune function, leading to life-threatening opportunistic infections and other therapy-related complications.

Early studies with ECP indicated that this therapy may be

Promising results with ECP in solid organ transplant rejection

Because graft rejection after organ transplantation is another T cell–mediated disease, ECP has been investigated in this indication. Early studies in small numbers of patients undergoing cardiac transplantation indicated that ECP plus conventional immunosuppressant treatment could reduce the incidence of rejection episodes among those at high risk of rejection, and reduce or reverse rejection in patients who have developed severe, recurrent, or refractory rejection.49, 50, 51, 52, 53 In

Promising pilot studies on ECP in CD

CD is a relapsing, progressive, T cell–mediated inflammatory disorder.65 Standard treatment consists of systemic steroids and salicylate for mild disease and systemic steroids, immunomodulators, and/or anti-tumor necrosis factor (TNF)-α inhibitors for moderate to severe disease. However, a large proportion of patients develop either steroid dependency or resistance, resulting in long-term use of high doses of these drugs and high risk of treatment-related complications. In a small preliminary

ECP in other diseases

A series of small open studies in patients with severe, treatment-resistant atopic dermatitis has indicated that ECP is effective in selected patients with this condition. Patients who failed to respond to standard first- and/or second-line therapies showed substantial skin responses to ECP treatment within 6 to 10 cycles.69, 70, 71 In the largest study to date, 35 patients with severe, therapy-resistant atopic dermatitis showed a significant overall reduction in Scoring of Atopic Dermatitis

Mechanism of action of ECP

While studies continue to accumulate showing the promising efficacy of ECP in many disease areas, progress is also being made in the search for understanding of the mechanisms of action, which will ultimately facilitate improvements in the use of this therapy.

Extracorporeally administered 8-MOP in the presence of UVA radiation forms covalent bonds with pyrimidine bases of nucleic acids, and DNA strand breaks are produced adjacent to these covalent bonds, along with cross-linking of DNA strands.

Safety and tolerability of ECP

ECP is a well-tolerated therapy. No significant side effects of this therapy have been reported in any of the conditions reviewed here, except for the short-term effects of oral 8-MOP when this was used in early studies. A reduction in red blood cell count and platelet count has been observed in some patients with acute GVHD. In addition, there is a risk of catheter-related infections if central venous lines are used, and rare cases of hypotension have been reported.33, 37, 47 Unlike other

Conclusions

ECP is an established first-line therapy for CTCL. This treatment has also now shown good efficacy in a number of other severe and difficult-to-treat conditions, such as systemic sclerosis, acute and chronic GVHD, and allograft rejection. Moreover, in a number of conditions, the use of ECP may allow many patients to reduce their use of systemic steroids and other immunosuppressants, thus reducing their long-term morbidity and mortality. The data accumulated during more than 20 years of use

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  • Cited by (0)

    Supported by an unrestricted educational grant from Therakos.

    Disclosure: Dr Knobler is a consultant, investigator, and speaker for Therakos. Dr Couriel is on the Advisory Board for Genzyme; is an investigator for Genzyme, Cephalon, and Astellas; and a speaker for Therakos, Schering Plough, Pfizer, Genzyme, Astellas, and Kirin. Dr Ferrara is a consultant for Therakos. Dr Jaksch is a speaker for Therakos. Dr Reinisch is a consultant, investigator, and speaker for Therakos. Dr Rook is a consultant for Merck and Graceway, and a speaker for Therakos and Eisai. Dr Schwarz is on the Advisory Board for Therakos, Novartis, Agiderm, Abbott, Intendis, Allmiral, and Genmab and a stockholder of Agiderm. Dr Greinix is on the Advisory Board and an investigator and speaker for Therakos. Drs Barr and French have no conflicts of interest to declare.

    This article was prepared by Ann McIlhinney, DPhil, of Anagram Communications Ltd, funded by Therakos, on behalf of the authors and is based on the presentations at a symposium held in the Vienna General Hospital of the Medical University of Vienna in 2007.

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