Thiotepa–melphalan myeloablative therapy for high-risk neuroblastoma

Background: Appropriate high-dose chemotherapy (HDC) for high-risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen that comprises two cycles of a total of 800 mg/m² of thiotepa and a total of 280 mg/m² of melphalan is widely utilized. Methods: To evaluate the safety and efficacy of this thiotepa–melphalan high-dose therapy for high-risk neuroblastoma, we reviewed the medical records of 41 patients with high-risk neuroblastoma who underwent this regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012. 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. Results: 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 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 with those with MYCN-nonamplified high-risk neuroblastoma (16.7 ± 8.8%; p <.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, three died because of regimen-related toxicity (infection, n = 2; microangiopathy, n = 1). Conclusion: The thiotepa–melphalan high-dose therapy with thiotepa and melphalan may be effective for high-risk neuroblastoma. However, this regimen is toxic and warrants special attention in clinical practice.