Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial
Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial
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DOI：
10.1016/s1470-2045(05)70291-6
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发表时间：
2005-09-01
期刊：
影响因子：
51.1
通讯作者：
Hero, B
中科院分区：
文献类型：
--
作者：
Berthold, F;Boos, J;Hero, B
背景骨髓清除疗法通常用于改善高危神经母细胞瘤患儿的预后，但其作用尚不明确。我们的目的是评估与维持化疗相比，自体干细胞移植的大治疗是否能提高无事件生存期和总生存期。方法295例高危神经母细胞瘤患者（即年龄大于1岁的4期疾病患者、mycn扩增肿瘤患者和1、2、3、4S期疾病患者或4期疾病患者且年龄小于1岁的患者）随机分配到自体干细胞移植的骨髓清除大疗法（美法兰、etoposide和卡铂）组（n=149）或口服环磷酰胺维持化疗组（n=146）。主要终点为无事件生存期。次要终点是总生存期和治疗相关死亡人数。分析分为意向治疗、被治疗和随机治疗。意向治疗分析显示，与分配维持治疗的患者相比，分配强化治疗的患者3年无事件生存率增加（47% [95% CI 38-55] vs 31% [95% Cl 23-39]；风险比1.404 [95% CI 1.048-1.8811, p=0.0221），但3年总生存率没有显著增加（62% [95% CI 54-701] vs 53% [95% CI 45-62]; 1.329 [0.958-1.8431, p=0.0875）。在治疗组（n=212）和随机治疗组（n=145）中，接受大剂量治疗的患者的3年无事件生存率和3年总生存率也有所提高。2例患者在诱导治疗期间死于治疗相关并发症。接受维持治疗的患者没有死于急性治疗相关的毒性反应。5例患者因急性并发症死亡。骨髓清除化疗联合自体干细胞移植可改善高危神经母细胞瘤患儿的预后，尽管治疗相关死亡风险增加。
Background Myeloablative megatherapy is commonly used to improve the poor outlook of children with high-risk neuroblastoma, yet its role is poorly defined. We aimed to assess whether megatherapy with autologous stem-cell transplantation could increase event-free survival and overall survival compared with maintenance chemotherapy.Methods 295 patients with high-risk neuroblastoma (ie, patients with stage 4 disease aged older than 1 year or those with MYCN-amplified tumours and stage 1, 2, 3, or 4S disease or stage 4 disease and < 1 year old) were randomly assigned to myeloablative megatherapy (melphalan, etoposide, and carboplatin) with autologous stem-cell transplantation (n=149) or to oral maintenance chemotherapy with cyclophosphamide (n=146). The primary endpoint was event-free survival. Secondary endpoints were overall survival and the number of treatment-related deaths. Analyses were done by intent to treat, as treated, and treated as randomised.Findings Intention-to-treat analysis showed that patients allocated megatherapy had increased 3-year event-free survival compared with those allocated maintenance therapy (47% [95% CI 38-55] vs 31% [95% Cl 23-39]; hazard ratio 1.404 [95% CI 1.048-1.8811, p=0.0221), but did not have significantly increased 3-year overall survival (62% [95% CI 54-701 vs 53% [95% CI 45-62]; 1.329 [0.958-1.8431, p=0.0875). Improved 3-year event-free survival and 3-year overall survival were also recorded for patients given megatherapy in the as-treated group (n=212) and in the treated-as-randomised group (n=145). Two patients died from therapy-related complications during induction treatment. No patients given maintenance therapy died from acute treatment-related toxic effects. Five patients given megatherapy died from acute complications related to megatherapy.Interpretation Myeloablative chemotherapy with autologous stem-cell transplantation improves the outcome for children with high-risk neuroblastoma despite the raised risk of treatment-associated death.