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Double-conditioning regimen with thiotepa and melphalan for high-risk Neuroblastoma
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  • Fumito Yamazaki,
  • Kai Yamasaki,
  • Chikako Kiyotani,
  • Yoshiko Hashii,
  • Yoko Shioda,
  • Junichi Hara,
  • Kimikazu Matsumoto
Fumito Yamazaki
National Center for Child Health and Development
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Kai Yamasaki
Osaka City General Hospital
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Chikako Kiyotani
National Center for Child Health and Development
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Yoshiko Hashii
Osaka University Graduate School of Medicine
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Yoko Shioda
National Center for Child Medical Health and Development
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Junichi Hara
Osaka City General Hospital
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Kimikazu Matsumoto
National Research Institute for Child Health and Development
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Abstract

Appropriate high-dose chemotherapy (HDC) for high-risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen (called double-conditioning regimen) comprising two cycles of total 800 mg/m2 of thiotepa and total 280 mg/m2 of melphalan is widely used. To re-evaluate the safety and the efficacy of this regimen for high-risk neuroblastoma, the medical records of 41 patients with high-risk neuroblastoma who underwent the double-conditioning regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012 were reviewed. MYCN-amplified high-risk neuroblastomas were observed in 23 patients. All patients underwent intensive multidrug induction chemotherapy, but none underwent anti-GD2 antibody immunotherapy. The primary tumor was resected at the adequate time point. The median follow-up duration for living patients was 9.2 years (range = 5.5–14.0 years). The 5-year event-free survival (EFS) and overall survival (OS) rates from treatment initiation were 41.5% ± 7.7% and 56.1% ± 7.8%, respectively. The 5-year EFS of MYCN-amplified high-risk neuroblastoma patients was 60.9% ± 10.2%, which was significantly superior compared to MYCN-non-amplified high-risk neuroblastoma patients (16.7% ± 8.8%; P < 0.001). MYCN amplification was the most favorable prognostic factor for EFS (hazard ratio = 0.29; 95% confidence interval = 0.12–0.66). Of the 41 patients, 3 died because of regimen-related toxicity (infection, n = 2; microangiopathy, n = 1). The double-conditioning regimen with thiotepa and melphalan is effective for high-risk neuroblastoma, especially in patients with MYCN amplification. However, the double-conditioning regimen is toxic and warrants special attention in clinical practice.

Peer review status:IN REVISION

24 May 2020Submission Checks Completed
24 May 2020Assigned to Editor
24 May 2020Submitted to Pediatric Blood & Cancer
26 May 2020Reviewer(s) Assigned
09 Jun 2020Review(s) Completed, Editorial Evaluation Pending
19 Jun 2020Editorial Decision: Revise Major
21 Aug 20201st Revision Received
21 Aug 2020Submission Checks Completed
21 Aug 2020Assigned to Editor
02 Sep 2020Reviewer(s) Assigned
17 Sep 2020Review(s) Completed, Editorial Evaluation Pending
18 Sep 2020Editorial Decision: Revise Minor