Children's Cancer Group trials of interleukin-2 therapy to prevent relapseof acute myelogenous leukemia

PURPOSE Up to 80% of children with acute myelogenous leukemia treated with intensiv e chemotherapy achieve remission; however, a large proportion of patients d evelops recurrent disease. Because interleukin (IL)-2 can induce remission in patients with overt evidence of acute myelogenous leukemia, we hypothesi zed that it might prevent relapse when administered to patients in first re mission after intensive consolidation chemotherapy. A pilot Children's Canc er Group (CCG) trial (CCG-0941) demonstrated the feasibility of this approa ch, and we initiated a prospective randomized trial (CCG-2961) to further e valuate the safety and potential efficacy of IL-2 therapy in preventing rel apse of acute myelogenous leukemia. PATIENTS AND METHODS In trial CCG-0941, 21 pediatric patients in complete remission following in duction and consolidation chemotherapy on protocol CCG-2941 received IL-2 t herapy. In CCG-2961, 79 patients in complete remission were randomized as o f February 1999 to receive either IL-2 (n = 39) or no further therapy. In b oth trials, recombinant IL-2 was given at a dose of 9 million IU/m(2)/d by continuous intravenous infusion for 4 days. After 4 days of rest, IL-2 was resumed at a dose of 1.6 million IU/m(2)/d for 10 days by continuous infusi on. We monitored patients for toxicity and relapse. RESULTS The majority of patients treated with IL-2 in these two trials expe rienced some degree of fever. Seven of 60 patients (12%) had clinically sig nificant rashes, and grade 3 vascular leak syndrome and hypotension have ea ch been observed in five patients (8%). Hypotension resolved promptly after treatment with intravenous fluids. No patients have experienced renal toxi city or required cardiac vasopressors or transfer to an intensive care unit ; there have been no treatment-related deaths. Overall, the incidence and s everity of adverse events remain similar in the two trials. Total projected accrual to the IL-2 randomization is anticipated to be 326 patients, and r elapse and survival data remain blinded. CONCLUSION The dose and schedule of IL-2 used in these two trials continue to be reasonably well tolerated by children with acute myelogenous leukemia in first remission. Any conclusions with regard to efficacy must await com pletion of the randomized trial.