Results of induction chemotherapy in children older than 18 months with stage-4 neuroblastoma treated with an adaptive-to-response modified N7 protocol (mN7)
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J. Mora [1] ; O. Cruz [1] ; C. Lavarino [1] ; J. Rios [2] ; M. Vancells [1] ; A. Parareda [1] ; H. Salvador [1] ; M. Suñol [1] ; R. Carrasco [1] ; A. Guillen [1] ; S. Mañé [3] ; C. de Torres [1]
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[1] Hospital Sant Joan de Deu
Hospital Sant Joan de Deu
Barcelona, España
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[2] Universitat Autònoma, Barcelona
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[3] CETIR Instituto de Medicina Nuclear, Barcelona
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- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 17, Nº. 7 (July), 2015, págs. 521-529
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
Purpose We report the response rate in children older than 18 months with stage 4 Neuroblastoma, using a modified dose-intensive, response-adaptive, induction mN7 protocol.
Methods From 2005 to 2012, 24 patients were treated with the mN7 protocol. Phase 1 included five MSKCC N7 cycles and surgery and two high-dose cyclophosphamide-topotecan (HD-CT) cycles for those who did not achieve complete remission (CR) and negative bone marrow (BM) minimal residual disease (MRD) status (CR+MRD-). Phase 2 consisted of myeloablative doses of topotecan, thiotepa and carboplatin plus hyperfractionated RT. Phase 3 included isotretinoin and 3F8 immunotherapy plus GM-CSF. BM MRD was monitored using GD2 synthase, PHOX2B and cyclin D1 mRNAs.
Results After 3 cycles, all patients showed BM complete histological clearance and 6 (25 %) were MRD-. Twenty of 21 s-look surgeries achieved macroscopic complete resection. After 5 cycles and surgery, 123I-MIBG scan was negative in 15 (62.5 %) cases, BM disease by histology was negative in 23 (96 %) and 10 (42 %) patients were MRD-. Twelve (50 %) pts were in CR, 2 in very good partial response (VGPR), 9 partial response (PR) and one had progressive disease. With 2 HD-CT extra cycles, 17 (71 %) pts achieved CR+MRD- status moving to phase 2. Overall and event-free survival at 3 years for the 17 patients who achieved CR+MRD- is 65 and 53 %, respectively, median follow-up 47 months. Seven (29 %) patients never achieved CR+MRD-. Univariate Cox regression analysis shows CR+MRD- status after mN7 induction as the only statistically significant prognostic factor to predict overall survival.
Conclusions mN7 induction regimen produced a CR+MRD- rate of 71 %. CR+MRD- status following induction was the only predictive marker of long-term survival.
