Clinical and Serologic Interleukin 2 Receptor α Response to Interleukin-2 in CCG-2961, a Ranomized Phase 3 Trial for Pediatric Acute Myeloid Leukemia.

The Children’s Cancer Group conducted a randomized comparison of interleukin-2 (IL-2) to no further therapy (control) in pediatric patients with acute myeloid leukemia in first remission after 3 courses of dose intensive chemotherapy. To assess biologic activity of IL-2, serum samples for soluble IL-2 receptor alpha concentration (sIL-2rα) were collected before induction chemotherapy, and after completing chemotherapy but before (day 0), during (day 4) and after IL-2 (day 18) in those randomized to receive IL-2 and before chemotherapy and at the end of chemotherapy (day 0) and 28 days later in the controls. Of 385 eligible patients, 289 consented to participation in the randomization, and 172 submitted specimens. Patients randomized to IL-2 received IL-2 9 x 106 IU/m²/day by continuous infusion (CI) days 0–3 and 1.6 x 106 IU/m²/day CI days 8–17. At five years disease-free survival (DFS) is 51% + 9% in the IL-2 group and 58% + 8% in the controls (p =0.489), and respective overall survivals are 70% + 8% and 73% + 8% (p= 0.727). At diagnosis, median sIL-2rα concentration was 3342 pg/ml in the IL-2 group (N=34) and 3778 pg/ml in the controls (N=41) (p=0.947). In both groups there was a significant reduction in sIL-2rα concentration between the start and day 0 after chemotherapy. In the IL-2 group median sIL-2rα increased significantly from 1462 pg/ml on day zero to 13659 pg/ml on day 4 (p<0.001) and 8435 pg/ml on day 18 (p<0.001). In the control group day sIL-2rα was 1424 pg/ml on day zero and 1559 pg/ml on day 28. Despite evidence of substantial biologic activity as measured by significant increases in sIL-2rα concentration during IL-2 administration, IL-2 in this dose and schedule had no significant effects on DFS or survival. Furthermore, sIL2αr levels (the pretreatment sIL2rα level, the sIL2rα level obtained after chemotherapy or the level achieved after IL2 treatment) did not correlate with DFS or survival, or treatment-related toxicity.