National Center for Child Health and Development, Children's Cancer Center, Tokyo, Japan.
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Pediatr Blood Cancer. 2021 Jun;68(6):e28896. doi: 10.1002/pbc.28896. Epub 2021 Mar 31.
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/m of thiotepa and a total of 280 mg/m 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 9.2 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).
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.
高危神经母细胞瘤的适当高剂量化疗（HDC）尚未确定。在日本，广泛使用一种独特的 HDC 方案，该方案包括两个周期，每个周期的噻替哌总量为 800mg/m，马法兰总量为 280mg/m。
为了评估噻替哌-马法兰高剂量治疗高危神经母细胞瘤的安全性和有效性，我们回顾了 2002 年至 2012 年间接受该方案治疗并随后进行自体外周血干细胞解救的 41 例高危神经母细胞瘤患者的病历。23 例患者存在 MYCN 扩增高危神经母细胞瘤。所有患者均接受强化多药诱导化疗，但均未接受抗 GD2 抗体免疫治疗。在适当的时间点切除原发肿瘤。
存活患者的中位随访时间为 9.2 年（范围为 5.5-14.0 年）。治疗开始时的 5 年无事件生存率（EFS）和总生存率分别为 41.5±7.7%和 56.1±7.8%。MYCN 扩增高危神经母细胞瘤患者的 5 年 EFS 为 60.9±10.2%，明显优于 MYCN 非扩增高危神经母细胞瘤患者（16.7±8.8%；p<.001）。MYCN 扩增是 EFS 的最有利预后因素（风险比=0.29；95%置信区间=0.12-0.66）。在 41 例患者中，有 3 例因方案相关毒性（感染 2 例，微血管病 1 例）死亡。
噻替哌和马法兰的噻替哌-马法兰高剂量治疗可能对高危神经母细胞瘤有效。然而，该方案具有毒性，在临床实践中需要特别注意。
