Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Pediatr Blood Cancer. 2012 Dec 15;59(7):1190-7. doi: 10.1002/pbc.24173. Epub 2012 Apr 10.
Outcome of high risk neuroblastoma (NBL) remains unsatisfactory in spite of intensive treatment efforts. Consolidation with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) has been intensified with tandem and triple cycles with promising results. Our purpose was to improve the outcome with two or three HD-consolidations.
Thirty six children with high risk NBL, diagnosed 1995-2010, had intensive induction and surgery, and were stratified to single, tandem or triple HD-therapy and ASCT, followed by local irradiation and cis-retinoic acid. In inoperable patients surgery was facilitated by preoperative HD-melphalan. Long-term outcome of our old cohort from 1987-1994 was updated.
Ten year event-free survival (EFS) from diagnosis was 0.44+/-0.10 of the old and 0.43+/-0.085 of the new cohort. EFS from the last ASCT was 0.53 +/-0.12 and 0.48+/-0.091, respectively. Preoperative HD-melphalan rendered 73% of bulky primaries operable in the new cohort. The 5-yr EFS from ASCT was 0.46+/-0.15 for single and 0.73+/-0.15 for tandem ASCT (P = 0.19). All triple ASCT patients, selected by poor/slow response, relapsed or died.
Thiotepa- and melphalan based HD regimens, with or without total body irradiation (TBI), appeared to give an outcome comparable to major NBL study groups with acceptable toxicity. Tandem HD therapy gave a 5-year EFS of 73%, whereas a third HD consolidation did not offer any additional advantage for ultra high risk patients with slow response. Pediatr Blood Cancer 2012; 59: 1190-1197. © 2012 Wiley Periodicals, Inc.
尽管进行了强化治疗，高危神经母细胞瘤（NBL）的治疗结果仍不尽如人意。高强度化疗（HD）联合自体干细胞移植（ASCT）的巩固治疗已采用串联和三联周期，取得了有希望的结果。我们的目的是通过两次或三次 HD 巩固治疗来改善治疗结果。
1995 年至 2010 年诊断的 36 例高危 NBL 患儿接受了强化诱导和手术治疗，并分层为单次、串联或三联 HD 治疗和 ASCT，随后进行局部放疗和维甲酸治疗。对于无法手术的患者，术前给予 HD 美法仑以促进手术。更新了我们 1987 年至 1994 年旧队列的长期结果。
从诊断到 10 年的无事件生存（EFS）率，旧队列为 0.44±0.10，新队列为 0.43±0.085。最后一次 ASCT 的 EFS 率分别为 0.53±0.12 和 0.48±0.091。新队列中，73%的大块原发性肿瘤在术前给予 HD 美法仑后可进行手术。单次 ASCT 的 5 年 EFS 率为 0.46±0.15，串联 ASCT 为 0.73±0.15（P=0.19）。所有选择进行三联 ASCT 的患者，由于反应差/缓慢，均复发或死亡。
基于噻替哌和马法兰的 HD 方案，无论是否联合全身照射（TBI），其疗效似乎与接受过可接受毒性治疗的主要 NBL 研究组相当。串联 HD 治疗可获得 5 年 EFS 率为 73%，而对于反应缓慢的超高危患者，第三次 HD 巩固治疗并没有带来任何额外优势。儿科血液肿瘤学 2012；59：1190-1197。©2012 年 Wiley 期刊
