Phase I-II study of interleukin-2 after high-dose chemotherapy and autologous bone marrow transplantation in poorly responding neuroblastoma.

ABSTRACT

Despite intensification of treatment with high-dose chemotherapy (HDC) and autologous bone marrow transplantation (AMBT), the prognosis of poorly responding metastatic neuroblastoma remains bad. Recombinant IL-2 (rIL-2) was used after ABMT to enhance the immune response against the tumor and thereby to improve survival of these patients. In this study, five courses of rIL-2 were administered as a continuous intravenous infusion every 2 weeks, the first course lasting 5 days, and the other four 2 days. rIL-2 treatment was to begin within 120 days of BMT. This study demonstrates the feasibility of rIL-2 soon after HDC and ABMT. The maximum tolerated dose (MTD) was 12 x 10(6) U/m2/day. Clinical toxicity was similar to that observed in adults, moderately increased by the proximity of ABMT; in a previous study we demonstrated that the MTD in non-grafted children was 18 x 10(6) U/M2/day. Nevertheless, half of the patients were not able to receive rIL-2 therapy after ABMT, and only 6/12 received 100% of the planned dose, mainly because of thrombocytopenia. If peripheral stem cell transplantation is demonstrated to enhance platelet recovery, more patients could be treated with rIL-2 with the present schedule. Earlier administration of low-dose rIL-2 after BMT associated with ex vivo rIL-2 treatment of the graft could be a more valid way of using rIL-2 to improve survival.