Comparison of Immunological and Molecular Markers When Using Interleukin-2 (IL-2) Alone or in Combination with γ-Interferon (IFN-γ) in the Maintenance Therapy of Acute Myeloid Leukemia (AML)

Since interleukin-2 (IL-2) has been shown to induce lysis of autologous AML blasts, maintenance therapy with IL-2 could be of value in AML. However, IL-2 normally is given at high doses, and side effects commonly occur. Low-dose regimens have been described [1]. Cytokines are capable of inducing other biological active mediators, and it is not known whether the in-vivo effects of low-dose IL-2 can be augmented by the addition of γ-IFN. We studied the biological effects of low-dose IL-2 alone or in combination with γ-interferon in the maintenance phase. AML patients were first treated using idarubicin and ara-C. 27 patients (25 de novo, 2 relapses) were enrolled in this study. Median age was 53γ (range 21–81). 10/27 patients were investigated using standard cytogenetics, of which 6 were abnormal (4 of these 6 revealed del (5q). 13 (48%) patients entered CR. As maintenance treatment 4-week cycles of either low-dose IL-2 alone or IL-2 in combination with γ-IFN were alternated. Patients were randomized to start with IL-2 cycles, or with IL-2 + γ-IFN. After each cycle, patients were crossed over to the other arm. By this method, 23 immunological and 9 molecular markers of 13 cycles with IL-2 alone and of 14 cycles of IL-2 + γ-IFN could be compared. No side effects were observed. Immunological analysis using two-color flow cytometry showed activation of T-cells in single patients. No difference between cycles with IL-2 alone as compared to IL-2 plus IFN-γ was observed with regard to activation of T-cells. However, an increase of B-cells was demonstrated when using the combination treatment compared to IL-2 alone. Polymerase chain reaction using primers specific for various human cytokines and the respective receptors (IL-2; IL-2 receptor; IL4; IL6; IFN-γ; GM-CSF) revealed no correlation with treatment. In conclusion, maintenance with low-dose IL-2 seems to be safe and is well tolerated; the only difference observed between the two cycles was an increase of B-cells in the cycles with IL-2 plus IFN-γ as compared to IL-2 alone.