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Detection of soluble interleukin‐2 receptor and interleukin‐10 in the serum of patients with aggressive non‐Hodgkin's lymphoma.Identification of a subset at high risk of treatment failure
Author(s) -
Stasi Roberto,
Zinzani Pier Luigi,
Galieni Piero,
Lauta Vito Michele,
Damasio Eugenio,
Dispensa Egidio,
Dammacco Franco,
Tura Sante,
Papa Giuseppe
Publication year - 1994
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19940915)74:6<1792::aid-cncr2820740623>3.0.co;2-f
Subject(s) - medicine , lymphoma , cytokine , chemotherapy , interleukin 2 , non hodgkin's lymphoma , receptor , gastroenterology , immunology
Background. This study explores the ability of the combined detection of soluble IL‐2 receptor (sIL‐2r) and interleukin‐10 (IL‐10) to predict treatment failure in patients with aggressive non‐Hodgkin's lymphoma (NHL) and to evaluate the modifications in cytokine measurements induced by the therapeutic administration of recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Methods. Serum levels of sIL‐2r and IL‐10 were measured serially in 93 patients with newly diagnosed aggressive NHL treated with four courses of a multiagent chemotherapy regimen. GM‐CSF was administered subcutaneously in 39 of these patients from day +5 to day +18 after each chemotherapy course. Results. Pretreatment levels of sIL‐2r were greatly elevated in patients with NHL compared with control subjects (P < 0.001), significantly correlating with the Ann Arbor stage ( P < 0.001) and β 2 ‐microglobulin (β 2 ‐m) concentrations (r = 0.552, P = 0.004). IL‐10 was detected in 37 patients at diagnosis, with no correlation with clinicohematologic parameters, and was not detected in the control sample ( P < 0.001). Cytokine and receptor levels progressively declined to normal ranges in responding patients, whereas they remained elevated in nonre‐sponders. During administration of GM‐CSF, the authors observed an increase of sIL‐2r, whereas lower elevations were recorded for IL‐10. However, on completion of the induction treatment, cytokine/receptor levels were comparable in patients with the same type of response, whether or not they had received GM‐CSF. In the five patients who were investigated at relapse, the levels of sIL‐2r, β 2 ‐m, and lactic dehydrogenase were found to be elevated. IL‐10 concentrations were high in three of these patients: two already had detectable levels at presentation, whereas one tested positive only on recurrence. No single parameter was associated with response to therapy, but the combination of elevated IL‐10 and sIL‐2r concentrations greater than 3000 U/ml resulted in a subset of eight patients who failed induction chemotherapy ( P < 0.001). In addition, six of eight patients with high IL‐10 and β 2 ‐m concentrations greater than 3.3 mg/I had an unfavorable outcome ( P = 0.003). A multivariate regression model was used to identify sIL‐2r ( P = 0.004) and β 2 ‐m ( P = 0.043) as the covariates that amplified the prognostic ability of IL‐10. Conclusions. sIL‐2r and IL‐10 measurements provide valuable information for better management of patients with NHL as markers to monitor disease activity and as prognostic indicators.