Posted March 1, 2011
Alan Siroy, MD, MPH
Cutaneous T-cell lymphoma (CTCL) is a general term used to describe a rare group of lymphoproliferative disorders characterized by clonally-derived, malignant T-cells manifesting as primary cutaneous lesions. The most common form of CTCL is mycosis fungoides (MF), comprising 60% of new diagnoses.1 MF patients present with skin patches, plaques, tumors, and/or erythroderma.2 Sézary syndrome (SS), the leukemic variant of MF, presents as erythroderma, pruritus, and circulating malignant T-cells in the peripheral blood (Sézary cells).2,3 Overall, bacteremia is the most common cause of death due to infected skin lesions.4
The particular stage of disease determines the management and prognosis of CTCL.5 Skin-directed treatments such as topical chemotherapy and phototherapy are often used for patients with early stage MF. Systemic treatments involving biologic therapy and chemotherapy (often in combination with skin-directed treatments) are used for more advanced-stage or refractory disease.6 Extracorporeal photopheresis (ECP) is a well-established therapy for CTCL and has been recommended as a first-line treatment for erythrodermic MF or SS.1,7,8 ECP is not curative for CTCL, as treatment is aimed at improvement of symptoms and skin appearance.4
ECP was first introduced as a treatment for CTCL in 1987 and was FDA approved based on a multicenter clinical trial that reported positive response in 73% of patients with advanced refractory CTCL.9 The treatment takes approximately three to -four hours and consists of three stages, which include: 1) leukapheresis, 2) photoactivation of white blood cells with psoralen and UVA light, and 3) reinfusion of the buffy coat.10 A standard therapeutic schedule consists of treatment for two consecutive days every two to four weeks for a minimum of six months.1,4,10,11 Erythrodermic CTCL is considered an American Society for Apheresis (ASFA) category I indication for ECP.3 Treatment of non-erythrodermic CTCL is a category III indication.4
ECP can be used as monotherapy or combined with other agents such as interferon alpha, interferon gamma, bexarotene, granulocyte macrophage colony-stimulating factor (GM-CSF), or retinoids.1 Studies involving the efficacy of ECP on CTCL patients have reported response rates ranging from 31–100% and complete response in up to 62% of patients.10 The treatment’s mechanisms of action include direct DNA damage and subsequent apoptosis of malignant lymphocytes, release of cytokines (eg, tumor necrosis factor-alpha) mediating anti-tumor effect, and activation of dendritic cells, which phagocytose the malignant T-cells and initiate a CD8+ immune response against the remaining clonal lymphocytes.12-15
Collaboration between clinicians and pathologists is essential in the successful management of the CTCL patient undergoing ECP therapy. Dermatopathologists make the histopathologic diagnosis of CTCL through skin biopsy examination, which classically shows epidermotropism with intra-epidermal atypical lymphocyte clusters (Pautrier’s microabscesses) and a lichenoid-to-diffuse lymphocytic infiltrate in the superficial dermis with immunohistochemical stains positive for most T-cell markers.16 Additionally, hematopathologists can diagnose Sézary syndrome through the morphologic identification of Sézary cells in the peripheral blood smear and confirmation by immunophenotypic analysis by flow cytometry.16 Either dermatologists or pathologists trained in apheresis medicine then administer ECP treatment.
In summary, CTCL is a rare group of disorders that may present with cutaneous and hematologic manifestations. MF (cutaneous) and SS (leukemic) are the most common subtypes of CTCL and may be treated using standard skin-based therapy and/or systemic treatments. ECP is an effective, apheresis-based therapy for CTCL that requires collaboration between clinicians and pathologists for effective patient management.
- Knobler R, Barr ML, Couriel DR, et al. Extracorporeal photopheresis: past, present, and future. J Am Acad Dermatol. 2009;61(4):652–665.
- Hwang ST, Janik JE, Jaffe ES, Wilson WH. Mycosis fungoides and Sézary syndrome. Lancet. 2008;371(9616):945–957.
- Siegel RS, Pandolfino T, Guitart J, Rosen S, Kuzel TM. Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol. 2000;18(15):2908–2925.
- Szczepiorkowski ZM, Winters JL, Bandarenko N, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. J Clin Apher. 2010;25(3):83–177.
- Kim EJ, Hess S, Richardson SK, et al. Immunopathogenesis and therapy of cutaneous T cell lymphoma. J Clin Invest. 2005;115(4):798–812.
- Gardner JM, Evans KG, Musiek A, Rook AH, Kim EJ. Update on treatment of cutaneous T-cell lymphoma. Curr Opin Oncol. 2009;21(2):131–137.
- Trautinger F, Knobler R, Willemze R, et al. EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer. 2006;42(8):1014–1030.
- Whittaker SJ, Marsden JR, Spittle M, Russell Jones R. Joint British Association of Dermatologists and UK Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas. Br J Dermatol. 2003;149(6):1095–1107.
- Edelson R, Berger C, Gasparro F, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987;316(6):297–303.
- Scarisbrick J. Extracorporeal photopheresis: what is it and when should it be used? Clin Exp Dermatol. 2009;34(7):757–760.
- Oliven A, Shechter Y. Extracorporeal photopheresis: a review. Blood Rev. 2001;15(2):103–108.
- Marks DI, Rockman SP, Oziemski MA, Fox RM. Mechanisms of lymphocytotoxicity induced by extracorporeal photochemotherapy for cutaneous T cell lymphoma. J Clin Invest. 1990;86(6):2080–2085.
- Vowels BR, Cassin M, Boufal MH, Walsh LJ, Rook AH. Extracorporeal photochemotherapy induces the production of tumor necrosis factor-alpha by monocytes: implications for the treatment of cutaneous T-cell lymphoma and systemic sclerosis. J Invest Dermatol. 1992;98(5):686–692.
- Edelson RL. Cutaneous T cell lymphoma: the helping hand of dendritic cells. Ann N Y Acad Sci. 2001;941:1–11.
- Berger CL, Hanlon D, Kanada D, Girardi M, Edelson RL. Transimmunization, a novel approach for tumor immunotherapy. Transfus Apher Sci. 2002;26(3):205–216.
- Vonderheid EC. On the diagnosis of erythrodermic cutaneous T-cell lymphoma. J Cutan Pathol. 2006;33 Suppl 1:27–42.
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