IMMUNOTHERAPY WITH LOW-DOSE RECOMBINANT INTERLEUKIN-2 AFTER HIGH-DOSECHEMOTHERAPY AND AUTOLOGOUS STEM-CELL TRANSPLANTATION IN NEUROBLASTOMA

The purpose of this study was to evaluate in a phase I-II trial whethe r low doses of recombinant human interleukin 2 (rHuIL-2) over a prolon ged period of time are safe and effective in eradicating or controllin g minimal residual disease in children with neuroblastoma given high-d ose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT ), From January 1992 to July 1996, 17 consecutive patients, with eithe r stage IV or relapsed neuroblastoma, were enrolled. Patients received rHuIL-2 after a median time interval (min-max) of 105 days (56-153) a fter HDCT and ASCT. The protocol consisted of 2 'priming' courses of r HuIL-2 at escalating doses administered intravenously at 72-h interval s, followed by 'maintenance' with 11 monthly and six bimonthly boostin g 5-day courses administered subcutaneously on an outpatient basis. At April 1997, 7 out of the 17 patients had completed the treatment sche dule, four had discontinued treatment because of toxicity and four bec ause of relapse; the remaining two patients are still on treatment, ha ving completed 15 courses. Expansion of T lymphocytes, together with a n increase in both natural killer cells and in activated T lymphocytes was evidenced. After a median (min-max) follow-up time of 30 (16-64) months, 12 out of 17 patients are alive and well, Two patients relapse d and died 14 and 35 months after transplant. Three patients are alive after having relapsed at 41, 21 and 13 months, The actuarial 2-year e vent-free survival and overall survival are 67% and 92% respectively. intermittent administration of low doses of rHuIL-2 given for a long p eriod of time is well tolerated and seems capable of controlling minim al residual disease after HDCT and ASCT in children with high-risk neu roblastoma.