Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma.
Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant 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 higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all 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 patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic 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 cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.
Department of Hematology, University of Rome Tor Vergata, Italy.
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R
Stasi
L
L
Zinzani
P
P
Galieni
V M
VM
Lauta
E
E
Damasio
E
E
Dispensa
F
F
Dammacco
A
A
Venditti
G
G
Del Poeta
M
M
Cantonetti
D000328:Adult; D016207:Cytokines / Q000097:blood*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018121:Receptors, Cytokine / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013997:Time Factors
D016207:Cytokines; D018121:Receptors, Cytokine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor