75% Complete Response and 15% Partial Response to Extracorporeal Photopheresis Combined With Other Therapies in Resistant Early Stage Cutaneous T-Cell Lymphoma

October 2016 | Volume 15 | Issue 10 | Original Article | 1212 | Copyright © 2016

Sila Seremet MD,a* Sunil Abhyankar MD,b* Tiffany J. Herd MD,b and Daniel Aires MDb

aIzmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey bThe University of Kansas, Kansas City, KS *Denotes co-first author

Abstract

INTRODUCTION: Extracorporeal photopheresis (ECP) has been used for the treatment of advanced stage or treatment refractory cutaneous T-cell lymphoma (CTCL) since 1987, and more recently has also been shown to be of benefit for earlier stage resistant CTCL. Complete response rates in prior studies of ECP in early CTCL have ranged from 0% to 40%. METHODS: We reviewed electronic medical records of all CTCL patients seen in the University of Kansas Cancer Center between June 2007 and May 2011. International review board approval was obtained. Inclusion criteria were (1) early stage CTCL and (2) ECP treatment. Data included demographics, type of intravenous access employed, CTCL subtype, cytogenetic features, adverse events, adjuvant treatments, and survival time in years. Treatment response was assessed via a modified severity weighted assessment tool (mSWAT). Primary outcome measures were response rates to ECP at 6 months and 12 months after beginning treatment. RESULTS: Of 20 patients (13 female; 7 male), 7 were Stage 1A, 11 were 1B, and 2 were 2A. Seven patients with stable disease and 2 patients with progression at 6 months received adjuvant therapy (PUVA/systemic retinoids/metotrexate/interferon) in addition to ECP. Twelve-month response to ECP was 90%: 15 patients (75%) had complete responses, 3 (15%) had partial responses, 1 had stable disease, and 1 progressed. CONCLUSION: Used alone or in combination with adjuvant treatments, ECP can be an effective treatment method in early stage CTCL.

J Drugs Dermatol. 2016;15(10):1212-1216.

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INTRODUCTION

Cutaneous T-cell lymphoma (CTCL) describes a heterogeneous group of lymphoproliferative disorders characterized by accumulation of malignant T–cell clones in skin, followed by other organs. Although not a common disease, incidence has been increasing both in United States and Europe.1Median survival time varies by stage; for early-stage CTCL confined to the skin (IA, IB, IIA) the median survival time is 10 to 12 years, whereas for late-stage disease involving extracutaneous sites (IIB-IV), it is less than 2 years.2 Therefore, skin-directed therapies are preferred in early stages, while systemic therapies are reserved for patients with progressive disease or for those who present at more advanced stages.3Extracorporeal photopheresis (ECP) combines leukapheresis and photodynamic therapy to treat certain blood diseases. In essence, ECP provides a means to administer PUVA systemically. It is now available at more than 200 centers worldwide.4 Advanced CTCL was the first disease for which ECP was evaluated. In Edelson’s initial 1987 study, 27 of 37 patients with otherwise resistant CTCL responded with an average 64% decrease in cutaneous involvement.5,6 In 1988, the UVAR photopheresis system was approved for treatment of CTCL skin manifestations recalcitrant to traditional treatments.The mechanism by which ECP works is not known, but a leading hypothesis is that psoralen-photoactivated circulating tumor cells are damaged by UVA and then stimulate an immune-mediated antitumor response following re-infusion.7 Another hypothesis suggests that ECP therapy directly alters components of the immune reaction against the malignant cells.6 Studies have reported increased post-ECP production of immunostimulatory mediators TNF-α and interleukin-6 in CTCL.7Although ECP was initially reserved for late stage disease (stages III-IV), it has more recently been used in patients in early stages (IA, IB, IIA, IIB) upresponsive to skin-directed therapies or with bulky disease.8 Complete response rates in early disease have ranged from 0% to 40% (Table 1A-E). For the past few years, our center has employed ECP in patients with early CTCL recalcitrant to other treatments. Non-ECP treatments such as topical steroids, retinoids, and narrowband UVB (NBUVB) were

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