Originally published as JCO Early Release 10.1200/JCO.2006.08.1331 on March 26 2007

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Plasma Cytokine and Soluble Receptor Signature Predicts Outcome of Patients With Classical Hodgkin's Lymphoma: A Study From the Groupe d'Etude des Lymphomes de l'Adulte

René-Olivier Casasnovas, Nicolas Mounier, Pauline Brice, Marine Divine, Franck Morschhauser, Jean Gabarre, Jean-Yves Blay, Laurent Voillat, Pierre Lederlin, Aspasia Stamatoullas, Jacques Bienvenu, Michel Guiguet, Liliane Intrator, Monique Grandjean, Josette Brière, Christophe Ferme, Gilles Salles

From the Hôpital Le Bocage, Dijon; Hôpital St-Louis; Hôpital Pitié Salpétrière, Paris; Hôpital Henri Mondor, Créteil; Centre Hospitalier Universitaire (CHU) Lille, Lille; Centre Léon Bérard, Lyon; Hôpital Jean Minjoz, Besançon; CHU Nancy, Nancy; Centre Henri Becquerel, Rouen; Hospices Civils de Lyon and Université Claude Bernard, Lyon; Institut Gustave Roussy, Villejuif, France

Address reprint requests to René-Olivier Casasnovas, MD, Service d'hématologie clinique, Hôpital Le Bocage, Centre Hospitalier Universitaire Dijon, Bd de Lattre de Tassigny, 21034 Dijon Cedex, France; e-mail: olivier.casasnovas{at}chu-dijon.fr

Purpose Approximately 15% of patients with localized and 30% with disseminated classical Hodgkin's lymphoma fail to respond or relapse after first-line treatment. Usual prognosis scoring systems are actually unable to identify this small subset of patients with good confidence, pointing out the need for additional prognostic biomarkers.

Patients and Methods We prospectively analyzed the prognosis value of plasma levels of tumor necrosis factor (TNF), its soluble receptors TNF-R1 and TNF-R2, IL-10, IL1-RA, IL-6, and soluble CD30 (sCD30) when taken before any treatment in 519 consecutive patients with a first diagnosis of classical Hodgkin's lymphoma.

Results Levels of TNF higher than 46 pg/mL, TNF-R1 higher than 3 ng/mL, TNF-R2 higher than 5 ng/mL, IL-10 higher than 30 pg/mL, IL1-RA higher than 668 pg/mL, IL-6 higher than 30 pg/mL, and sCD30 higher than 80 U/mL were associated with poor event-free and overall survival. In multivariate analysis, high levels of IL1-RA, IL-6, and sCD30 were independent poor prognosis factors, and the cytokine signature based on their combination allowed the stratification of patients in four prognosis classes, reaching a 5-year event-free survival probability of 92%, 85%, 76%, and 15%, respectively. This index was more potent than other scoring systems to predict patient event-free survival, and remained independent from the international prognostic score (P < .001), adding significant prognostic information to its predictive power.

Conclusion Plasma cytokine signature is sufficient to predict disease-related outcome in classical Hodgkin's lymphoma, and allows the identification of patients with very high risk of treatment failure.

published online ahead of print at www.jco.org on March 26, 2007.

Supported by Grant No. PHRC 1998 from the French government.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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