Purpose Delayed intensification (DI) is an integral part of treatment of childhood acute lymphoblastic leukemia (ALL), but it is associated with relevant toxicity. Therefore, standard-risk patients of trial AIEOP-BFM ALL 2000 (Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With ALL) were investigated with the specific aim to reduce treatment intensity. Patients and Methods Between July 2000 and July 2006, 1,164 patients (1 to 17 years of age) with standard-risk ALL (defined as the absence of high-risk cytogenetics and undetectable minimal residual disease on days 33 and 78) were randomly assigned to either experimental reduced-intensity DI (protocol III; P-III) or standard DI (protocol II; P-II). Cumulative drug doses of P-III were reduced by 30% for dexamethasone and 50% for vincristine, doxorubicin, and cyclophosphamide, which shortened the treatment duration from 49 to 29 days. The study aimed at noninferiority of reduced-intensity P-III; analyses were performed according to treatment given. Results For P-III and P-II, respectively, the 8-year rate of disease-free survival (± SE) was 89.2 ± 1.3% and 92.3 ± 1.2% ( P = .04); cumulative incidence of relapse, 8.7 ± 1.2% and 6.4 ± 1.1% ( P = .09); and overall survival, 96.1 ± 0.8% and 98.0 ± 0.6% ( P = .06). Patients with ETV6-RUNX1-positive ALL and patients 1 to 6 years of age performed equally well in both arms. The incidence of death during remission was comparable, which indicates equivalent toxicity. The 8-year cumulative incidence rate of secondary malignancies was 1.3 ± 0.5% and 0.6 ± 0.4% for P-III and P-II, respectively ( P = .37). Conclusion Although the criteria used for the standard-risk definition in this trial identified patients with exceptionally good prognosis, reduction of chemotherapy was not successful mainly because of an increased rate of relapse. The data suggest that treatment reduction is feasible in specific subgroups, which underlines the biologic heterogeneity of this cohort selected according to treatment response.

中文翻译：

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由检测不到的微小残留疾病定义的标准风险小儿急性淋巴细胞白血病的强度降低延迟强化：国际随机试验的结果 (AIEOP-BFM ALL 2000)

目的延迟强化 (DI) 是儿童急性淋巴细胞白血病 (ALL) 治疗的一个组成部分，但它与相关毒性有关。因此，对试验 AIEOP-BFM ALL 2000（基于复发风险的联合化疗治疗年轻 ALL 患者）的标准风险患者进行了调查，具体目的是降低治疗强度。患者和方法 2000 年 7 月至 2006 年 7 月，1,164 名标准风险 ALL 患者（1 至 17 岁）（定义为在第 33 和 78 天没有高风险细胞遗传学和检测不到微小残留病）被随机分配到实验性降低强度 DI（协议 III；P-III）或标准 DI（协议 II；P-II）。P-III 的累积药物剂量对于地塞米松减少了 30%，对于长春新碱、多柔比星、和环磷酰胺，将治疗时间从 49 天缩短到 29 天。该研究旨在降低强度 P-III 的非劣效性；根据给予的治疗进行分析。结果 对于 P-III 和 P-II，8 年无病生存率 (± SE) 分别为 89.2 ± 1.3% 和 92.3 ± 1.2% ( P = .04)；复发的累积发生率，8.7 ± 1.2% 和 6.4 ± 1.1% (P = .09)；和总生存率分别为 96.1 ± 0.8% 和 98.0 ± 0.6% ( P = .06)。ETV6-RUNX1 阳性 ALL 患者和 1 至 6 岁患者在两组中的表现同样出色。缓解期间的死亡发生率相当，这表明毒性相当。P-III 和 P-II 继发性恶性肿瘤的 8 年累积发病率分别为 1.3 ± 0.5% 和 0.6 ± 0.4% ( P = .37)。结论 尽管该试验中用于标准风险定义的标准确定了预后非常好的患者，但减少化疗并不成功，主要是因为复发率增加。数据表明，在特定亚组中减少治疗是可行的，这强调了根据治疗反应选择的该队列的生物学异质性。