Background: Randomized trials have demonstrated improved survival of high-risk neuroblastoma patients after myeloablative chemotherapy (MAT) with autologous stem cell transplantation (ASCT) compared to oral continuation chemotherapy (CC). This effect, however, could either be due to better cure rates or to delay of relapses. Therefore, we have re-analyzed the patient cohort of the randomized trial NB97 in order to find whether the survival benefit of MAT and ASCT is stable during long term follow-up.
Methods: Patients with stage 4 neuroblastoma older than 12 months and all patients with MYCN amplification were eligible. Treatment consisted of six-cycle induction chemotherapy, primary site tumor resection, consolidation either with MAT/ASCT or CC, MIBG therapy for MIBG avid residual disease, radiation therapy for active local disease present after operation, and post-consolidation therapy either with single drug anti-GD2 antibody ch14.18 or with 13-cis-retinoic acid. Outcome was analyzed by logrank test and Cox regression analysis.
Results: A total of 295 patients were randomized. The median observation time was 11.6 years. The 10 year event-free survival (10yEFS) was 40.0+/-4.0% in 149 patients randomized for MAT and 29.4+/-3.8% in 146 patients randomized for CC (p=0.027). The 10 year overall survival was 55.2+/-4.1% and 44.6+/-4.2% in patients randomized for MAT and CC, respectively (p=0.077). The last relapse occurred 12.7 years after diagnosis, so far. In the subgroup of stage 4 patients >18 months at diagnosis randomization for MAT was associated with better EFS (p=0.023) and a trend for better OS (p=0.098). Multivariable analysis identified stage, MYCN status, age, MAT, and treatment with ch14.18 as independent prognostic factors for EFS and also for OS.
Conclusion: Intensive multimodality treatments can achieve survival rates of 50% in high-risk neuroblastoma patients. The benefit of MAT with ASCT is due to improved cure rates and not to delay of relapses.