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Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy

Thorsten Simon1*, Barbara Hero1, Andreas Faldum2, Rupert Handgretinger3, Martin Schrappe4, Thomas Klingebiel5 and Frank Berthold1

Author Affiliations

1 Children's Hospital, University of Cologne, Cologne, Germany

2 Institute for Medical Biostatistics and Clinical Research, University of Münster, Münster, Germany

3 Children's Hospital, University of Tübingen, Tübingen, Germany

4 Children's Hospital, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany

5 Johann Wolfgang Goethe University, Department of Pediatrics III, Frankfurt/Main, Germany

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BMC Cancer 2011, 11:21  doi:10.1186/1471-2407-11-21

Published: 18 January 2011



The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort.


A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls.


The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found.


Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.