Combined Therapy for Sézary Syndrome with Extracorporeal Photochemotherapy and Low-Dose Interferon Alfa Therapy: Clinical, Molecular, and Immunologic Observations

Extracorporeal photochemotherapy is a well-tolerated treatment of palliative benefit for patients with the Sézary syndrome, but up to 25% of patients do not respond to this form of therapy. Interferon alfa is a glycoprotein with immunomodulatory properties that is also an active agent in the treatment of Sézary syndrome; however, dose-related toxic effects often limit its long-term use. A patient with rapidly advancing Sézary syndrome was treated with a combination of extracorporeal photochemotherapy and low doses of subcutaneous interferon alfa-2b. In addition to the almost complete clearing of his skin lesions and the marked diminution of his extensive lymphadenopathy after 16 weeks of combined therapy, disappearance of the malignant T-cell clone from the peripheral blood was documented by Southern blot analysis. Normalization of the peripheral blood lymphocyte phenotypic profile and an increase in natural killer cell activity were also observed. The excellent clinical response to combined therapy has been sustained, without adverse effects, during 18 months of treatment and 22 months of continued follow-up. The long-term disappearance of the malignant clone from the blood of a patient with Sézary syndrome in response to therapy has not been previously described and thus represents a novel observation. Extracorporeal photochemotherapy and low-dose interferon alfa are well-tolerated therapies that, when combined, may have additive efficacy in the treatment of Sézary syndrome. These results suggest that further exploration of this therapeutic combination is warranted.