Mora J, Cruz O, Lavarino C, Rios J, Vancells M, Parareda A, Salvador H, Suñol M, Carrasco R, Guillen A, Mañé S, de Torres C
Department of Oncology, Hospital Sant Joan de Déu, Barcelona, Passeig Sant Joan de Déu, 2, Esplugues de Llobregat, 08950, Barcelona, Spain,
Clin Transl Oncol. 2015 Jul;17(7):521-9. doi: 10.1007/s12094-014-1273-8. Epub 2015 Jan 17.
We report the response rate in children older than 18 months with stage 4 Neuroblastoma, using a modified dose-intensive, response-adaptive, induction mN7 protocol.
From 2005 to 2012, 24 patients were treated with the mN7 protocol. Phase 1 included five MSKCC N7 cycles and surgery and two high-dose cyclophosphamide-topotecan (HD-CT) cycles for those who did not achieve complete remission (CR) and negative bone marrow (BM) minimal residual disease (MRD) status (CR+MRD-). Phase 2 consisted of myeloablative doses of topotecan, thiotepa and carboplatin plus hyperfractionated RT. Phase 3 included isotretinoin and 3F8 immunotherapy plus GM-CSF. BM MRD was monitored using GD2 synthase, PHOX2B and cyclin D1 mRNAs.
After 3 cycles, all patients showed BM complete histological clearance and 6 (25 %) were MRD-. Twenty of 21 s-look surgeries achieved macroscopic complete resection. After 5 cycles and surgery, (123)I-MIBG scan was negative in 15 (62.5 %) cases, BM disease by histology was negative in 23 (96 %) and 10 (42 %) patients were MRD-. Twelve (50 %) pts were in CR, 2 in very good partial response (VGPR), 9 partial response (PR) and one had progressive disease. With 2 HD-CT extra cycles, 17 (71 %) pts achieved CR+MRD- status moving to phase 2. Overall and event-free survival at 3 years for the 17 patients who achieved CR+MRD- is 65 and 53 %, respectively, median follow-up 47 months. Seven (29 %) patients never achieved CR+MRD-. Univariate Cox regression analysis shows CR+MRD- status after mN7 induction as the only statistically significant prognostic factor to predict overall survival.
mN7 induction regimen produced a CR+MRD- rate of 71 %. CR+MRD- status following induction was the only predictive marker of long-term survival.
我们报告了采用改良的剂量密集、反应适应性诱导mN7方案治疗18个月以上4期神经母细胞瘤患儿的缓解率。
2005年至2012年，24例患者接受了mN7方案治疗。第1阶段包括5个MSKCC N7周期及手术，对于未达到完全缓解（CR）且骨髓（BM）微小残留病（MRD）状态为阴性（CR+MRD-）的患者，给予2个高剂量环磷酰胺-拓扑替康（HD-CT）周期。第2阶段包括大剂量拓扑替康、噻替派和卡铂加超分割放疗。第3阶段包括异维甲酸和3F8免疫治疗加粒细胞-巨噬细胞集落刺激因子（GM-CSF）。使用GD2合酶、PHOX2B和细胞周期蛋白D1 mRNA监测BM MRD。
3个周期后，所有患者均显示BM组织学完全清除，6例（25%）为MRD-。21例中期评估手术中有20例实现了宏观完全切除。5个周期及手术后，15例（62.5%）患者的（123）I-MIBG扫描为阴性，23例（96%）患者的BM组织学疾病为阴性，10例（42%）患者为MRD-。12例（50%）患者达到CR，2例为非常好的部分缓解（VGPR），9例为部分缓解（PR），1例疾病进展。通过额外2个HD-CT周期，17例（71%）患者达到CR+MRD-状态并进入第2阶段。17例达到CR+MRD-的患者3年总生存率和无事件生存率分别为65%和53%，中位随访47个月。7例（29%）患者从未达到CR+MRD-。单因素Cox回归分析显示，mN7诱导后CR+MRD-状态是预测总生存的唯一具有统计学意义的预后因素。
mN7诱导方案产生了71%的CR+MRD-率。诱导后CR+MRD-状态是长期生存的唯一预测指标。
