Thiotepa-melphalan myeloablative therapy for high-risk neuroblastoma.

Abstract

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 800mg/m2 of thiotepa and a total of 280mg/m2 of melphalan is widely utilized. 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. The median follow-up duration for living patients was 9.2years (range 5.5-14.0years). 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). 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.