Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Dutch Childhood Oncology Group (DCOG), Utrecht, the Netherlands.
J Clin Oncol. 2023 Sep 1;41(25):4130-4142. doi: 10.1200/JCO.22.02705. Epub 2023 Jul 17.
The ALL10 protocol improved outcomes for children with ALL by stratifying and adapting therapy into three minimal residual disease-defined risk groups: standard risk, medium risk (MR), and high risk. -deleted (del) ALL in the largest MR group still showed poor outcome, in line with protocols worldwide, accounting for a high number of overall relapses. ALL10 showed high toxicity in Down syndrome (DS) and excellent outcome in ALL. Poor prednisone responders (PPRs) were treated as high risk in ALL10. In ALL11, we prolonged therapy for del from 2 to 3 years. We reduced therapy for DS by omitting anthracyclines completely, for in intensification, and for PPR by treatment as MR.
Eight hundred nineteen patients with ALL (age, 1-18 years) were enrolled on ALL11 and stratified as in ALL10. Results were compared with those in ALL10.
The five-year overall survival (OS), event-free survival (EFS), cumulative risk of relapse (CIR), and death in complete remission on ALL11 were 94.2% (SE, 0.9%), 89.0% (1.2), 8.2% (1.1), and 2.3% (0.6), respectively. Prolonged maintenance for del MR improved 5-year CIR by 2.2-fold (10.8% 23.4%; = .035) and EFS (87.1% 72.3%; = .019). Landmark analysis at 2 years from diagnosis showed a 2.9-fold reduction of CIR (25.6%-8.8%; = .008) and EFS improvement (74.4%-91.2%; = .007). Reduced therapy did not abrogate 5-year outcome for (EFS, 98.3%; OS, 99.4%), DS (EFS, 87.0%; OS, 87.0%), and PPR (EFS, 81.1%; OS, 94.9%).
Children with del ALL seem to benefit from prolonged maintenance therapy. Chemotherapy was successfully reduced for patients with , DS, and PPR ALL. It has to be noted that these results were obtained in a nonrandomized study using a historical control group.
ALL10 方案通过将三种微小残留病定义的风险组（标准风险、中危（MR）和高危）分层并调整治疗方法，改善了儿童 ALL 的预后。在最大的 MR 组中，del ALL 仍然表现出不良结局，与全球方案一致，导致总体复发率较高。ALL10 方案在唐氏综合征（DS）中具有高毒性，但 ALL 的结果良好。ALL10 方案中，泼尼松反应不良（PPR）患者被视为高危。在 ALL11 中，我们将 del 的治疗时间从 2 年延长至 3 年。我们通过完全省略蒽环类药物来减少 DS 的治疗，在强化治疗中减少 ，并通过 MR 治疗 PPR。
819 例 ALL 患儿（年龄 1-18 岁）入组 ALL11，并按 ALL10 进行分层。结果与 ALL10 进行比较。
ALL11 的 5 年总生存（OS）、无事件生存（EFS）、累积复发率（CIR）和完全缓解时的死亡率分别为 94.2%（SE，0.9%）、89.0%（1.2%）、8.2%（1.1%）和 2.3%（0.6%）。del MR 的延长维持治疗使 5 年 CIR 提高了 2.2 倍（10.8% 23.4%； =.035）和 EFS（87.1% 72.3%； =.019）。从诊断开始的 2 年时间标记分析显示 CIR 降低了 2.9 倍（25.6%-8.8%； =.008），EFS 改善（74.4%-91.2%； =.007）。减少治疗并未改变 5 年预后（EFS，98.3%；OS，99.4%）、DS（EFS，87.0%；OS，87.0%）和 PPR（EFS，81.1%；OS，94.9%）。
del ALL 患儿似乎受益于延长维持治疗。对于 、DS 和 PPR ALL 患者，化疗已成功减少。需要注意的是，这些结果是在使用历史对照的非随机研究中获得的。
