CLINICAL IMPLICATIONS OF CYTOKINE AND SOLUBLE RECEPTOR MEASUREMENTS IN PATIENTS WITH NEWLY-DIAGNOSED AGGRESSIVE NON-HODGKINS-LYMPHOMA

Serum levels of 13 different cytokines and receptors were measured ser ially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) trea ted by 4 cycles of an intensive multi-agent chemotherapy regimen. Reco mbinant human granulocyte-macrophage colony-stimulating factor (GM-CSF ) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly high er pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 recepto r (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, w ere observed in NHL patients as compared to controls (p < 0.001 for al l molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patien ts presenting B symptoms (p < 0.001). Cytokine levels progressively de clined to normal ranges in responding patients, while they remained el evated in non-responders. Relapsed patients also presented increased c oncentrations of several molecules. During the administration of GM-CS F, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosi s factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon comp letion of the induction treatment, cytokine/receptor levels were compa rable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prog nostic significance, but the combination of elevated IL-10 and of sIL- 2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytok ine and soluble receptor measurements can provide valuable information s for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.