Outcome of high-risk neuroblastoma using a dose intensity approach:: Improvement in initial but not in long-term results

Background. Stage 4 and MYCN amplified (MNA) neuroblastoma in children have a poor prognosis. Our aim was to increase initial and long-term reponse in this population. Procedure. High-risk children vvere studied according to the International Neuroblastoma Staging System, then treated with high-dose cyclophosphamide and high-dose carboplatin, followed by surgery and autologous stern cell transplant or maintenance chemotherapy. Results. From June 1992 to December 1998, 83 children were admitted in the study (72 stage 4 > 1 year, 5 stage 4 MNA infants, and 6 MNA stage 3 children); tumor tissue was obtained from 73, MYCN was performed in 65, being amplified in 21 (32%). Induction chemotherapy Aas administered in the expected time in 35% of patients. Its toxicity was mainly hematologic followed by infections, and there were 3 chemotherapy-related deaths. Delayed surgery was performed on 60 patients with complete or > 90% resection in 80% of cases. Chemotherapy plus surgery produced some response in 90% of patients, 53% were in CR/VGPR; 49 children received autologous SCT, and 16 received maintenance chemotherapy for 9 months. Follow-up ranges are 1-87 months, mean 30 months. S and EFS at 4 years are 0.33 (SD 0.02). Conclusions. High-dose cyclophosphamide and high-dose carboplatin are effective in the initial treatment of neuroblastoma; combined with surgery they produce some response in most patients. Nevertheless, the CR/VGPR rate reaches only 53%, Survival time has also been prolonged but most patients relapse with metastases. (C) 2001 Wiley-Liss, Inc.