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.

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.

Contribution of the Platelia Candida-specific antibody and antigen tests to early diagnosis of systemic Candida tropicalis infection in neutropenic adults.

The Platelia Candida-specific antigen and antibody assays (Bio-Rad Laboratories) were used to test serial serum samples from seven neutropenic adult patients with hematological malignancies who had developed systemic Candida tropicalis infections. The diagnosis of candidiasis was based on a positive blood culture (all seven patients) and the isolation of C. tropicalis from a normally sterile site (six patients). All patients received early antifungal therapy with amphotericin B and/or an azole derivative and had successful outcomes. When the combined assays were applied to sera collected at different time points before and after the first positive blood culture, all patients tested positive. In six patients, at least one positive test was obtained with sera collected, on average, 5 days (range, 2 to 10 days) prior to the first positive blood culture, while blood cultures were constantly negative. High and persistent mannanemias were detected in all patients during the neutropenic period. In five patients, an increased antibody response was detected when the patients recovered from aplasia. Controls consisted of 48 serum samples from 12 febrile neutropenic patients with aspergillosis (n = 4), bacteremia (n = 4), or no evidence of infection (n = 4). A low level of mannanemia was detected in only one serum sample, and none showed significant Candida antibody titers. Our data thus confirm the value of the combined detection of mannanemia and antimannan antibodies in individuals at risk of candidemia and suggest that in neutropenic patients, an approach based on the regular monitoring of both markers could contribute to the earlier diagnosis of C. tropicalis systemic infection.