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Original Article
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Volume 354:709-718 February 16, 2006 Number 7
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Prognostic Significance of Autoimmunity during Treatment of Melanoma with Interferon
Helen Gogas, M.D., John Ioannovich, M.D., Urania Dafni, Sc.D., Catherine Stavropoulou-Giokas, M.D., Konstantina Frangia, M.D., Dimosthenis Tsoutsos, M.D., Petros Panagiotou, M.D., Aristidis Polyzos, M.D., Othonas Papadopoulos, M.D., Alexandros Stratigos, M.D., Christos Markopoulos, M.D., Dimitrios Bafaloukos, M.D., Dimitrios Pectasides, M.D., George Fountzilas, M.D., and John M. Kirkwood, M.D.

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ABSTRACT

Background Immunotherapy for advanced melanoma induces serologic and clinical manifestations of autoimmunity. We assessed the prognostic significance of autoimmunity in patients with stage IIB, IIC, or III melanoma who were treated with high-dose adjuvant interferon alfa-2b.

Methods We enrolled 200 patients in a substudy of a larger, ongoing randomized trial. Blood was obtained before the initiation of intravenous interferon therapy, after 1 month of therapy, and at 3, 6, 9, and 12 months. Serum was tested for antithyroid, antinuclear, anti-DNA, and anticardiolipin autoantibodies, and patients were examined for vitiligo.

Results The median duration of follow-up was 45.6 months. Relapse occurred in 115 patients, and 82 patients died. The median relapse-free survival was 28.0 months, and the median overall survival was 58.7 months. Autoantibodies and clinical manifestations of autoimmunity were detected in 52 patients (26 percent). The median relapse-free survival was 16.0 months among patients without autoimmunity (108 of 148 had a relapse) and was not reached among patients with autoimmunity (7 of 52 had a relapse). The median survival was 37.6 months among patients without autoimmunity (80 of 148 died) and was not reached among patients with autoimmunity (2 of 52 died). In univariate and multivariate regression analyses, autoimmunity was an independent prognostic marker for improved relapse-free survival and overall survival (P<0.001).

Conclusions The appearance of autoantibodies or clinical manifestations of autoimmunity during treatment with interferon alfa-2b is associated with statistically significant improvements in relapse-free survival and overall survival in patients with melanoma.


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From the First Department of Medicine, Laiko Hospital (H.G., A.P., C.M., D.B., D.P., G.F.) and the Department of Dermatology, Andreas Sygros Hospital (O.P., A.S.), National and Kapodistrian University of Athens; the Department of Plastic Surgery and Microsurgery (J.I., D.T., P.P.) and the Department of Immunology and National Tissue Typing Center (C.S.-G.), General Hospital of Athens; the Laboratory of Biostatistics, University of Athens School of Nursing (U.D.); and the Department of Pathology, Sotiria General Hospital, World Health Organization Melanoma Program (K.F.) — all in Athens, Greece; and the University of Pittsburgh Cancer Institute, Pittsburgh (J.M.K.).

Address reprint requests to Dr. Gogas at the University of Athens, First Department of Medicine, P.O. Box 14120, 115 10 Athens, Greece, or at hgogas{at}hol.gr.

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