Klingebiel T, Bader P, Bares R, Beck J, Hero B, Jürgens H, Lang P, Niethammer D, Rath B, Handgretinger R
Childrens Hospital, University of Tübingen, Germany.
Eur J Cancer. 1998 Aug;34(9):1398-402. doi: 10.1016/s0959-8049(98)00130-0.
Disseminated neuroblastoma after infancy has a prognosis of approximately 10-20% with conventional therapy. We investigated the role of high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) rescue in combination with 131I-metaiodobenzylguanidine ([131I-m]IBG). 11 children with neuroblastoma stage 4 were pretreated within the German Neuroblastoma Trial NB90 and included in a high-dose concept for consolidation. Remission was documented by ultrasound, CT, NMR, or [123I-m]IBG scanning. HDCT was a combination of melphalan (180 mg/m2), carboplatin (1,500 mg/m2) and etoposide (40 mg/kg). All children were treated by [131I-m]IBG (0.58 GBq/kg) prior to high-dose treatment. All 11 children were additionally treated with antiGD2 murine- or chimeric-antibody (ch14.18). 4 children had no change to their remission status but three achieved a complete response (from a partial response to first line) and one a partial response (from no response to first line). The other 3 children progressed, 2 dying of their disease. Using Kaplan-Meier analysis, the probability of progression-free survival was 0.70 +/- 0.15 with a median observation time of 19 months. 9/11 children are alive, 8 without progression or relapse, whilst 2 have died of their disease. The combination of mIBG plus high-dose chemotherapy with PBSC support supplemented by immunotherapy with antiGD2 antibody appears to be a feasible and effective treatment regimen for disseminated neuroblastoma in this limited series. Larger numbers of patients should be treated to confirm these results.
婴儿期后的播散性神经母细胞瘤采用传统疗法的预后约为10%-20%。我们研究了大剂量化疗（HDCT）联合外周血干细胞（PBSC）救援及131I-间碘苄胍（[131I-m]IBG）的作用。11例4期神经母细胞瘤患儿在德国神经母细胞瘤试验NB90中接受预处理，并纳入巩固治疗的大剂量方案。通过超声、CT、核磁共振或[123I-m]IBG扫描记录缓解情况。HDCT方案为美法仑（180 mg/m2）、卡铂（1500 mg/m2）和依托泊苷（40 mg/kg）联合应用。所有患儿在大剂量治疗前均接受[131I-m]IBG（0.58 GBq/kg）治疗。所有11例患儿均额外接受了抗GD2鼠源或嵌合抗体（ch14.18）治疗。4例患儿的缓解状态无变化，但3例实现了完全缓解（从一线治疗的部分缓解到完全缓解），1例实现了部分缓解（从一线治疗的无缓解到部分缓解）。另外3例患儿病情进展，2例死于疾病。采用Kaplan-Meier分析，无进展生存期的概率为0.70±0.15，中位观察时间为19个月。11例患儿中有9例存活，8例无进展或复发，2例死于疾病。在这个有限的病例系列中，mIBG加大剂量化疗联合PBSC支持并辅以抗GD2抗体免疫治疗似乎是播散性神经母细胞瘤一种可行且有效的治疗方案。需要治疗更多患者以证实这些结果。
