Reducing Daunorubicin in Induction Therapy in Children With B-Lineage ALL With Favorable Prognosis: Results of Phase III Trial AIEOP-BFM ALL 2009.

Acute and late sequelae of anthracyclines are of major concern.

蒽环类药物的急性和晚期后遗症引起了重大关注。

The AIEOP-BFM ALL 2009 trial aimed to clarify the need for anthracyclines in low-risk patients.

AIEOP-BFM ALL 2009试验旨在阐明低危患者中葱环类药物的必要性。

patients_and_methods

After 2 weeks of induction therapy, which included two daunorubicin (DNR) doses once weekly (30 mg/m2 each) as part of a 4-drug therapy, patients age 1-17 years with newly diagnosed non-high-risk B-ALL either positive for ETV6::RUNX1 or with rapid treatment response, as assessed by induction day-15 evaluation, were randomly assigned to receive either two additional doses of DNR (control arm [CA]) or no further DNR during induction (experimental arm [EA]).

在为期两周的诱导治疗后，该治疗包括每周一次的两剂柔红霉素（DNR）（每剂30 mg/m2），作为四药疗法的一部分，年龄在1-17岁之间、新诊断为非高危B-ALL的患者，如果ETV6::RUNX1阳性或通过第15天的诱导评估显示出快速治疗反应，则随机分配至接受额外两剂DNR（对照组[CA]）或在诱导期间不再接受DNR（实验组[EA]）。

Patients treated as randomly assigned were included in the primary analysis on noninferiority in event-free survival (EFS).

随机分配接受治疗的患者被纳入主要分析，以评估无事件生存（EFS）的非劣效性。

Adverse reactions of special interest (ARSI) were analyzed in the as-treated population.

在按治疗方案接受治疗的人群中分析了特别关注的不良反应（ARSI）。

Results

Of 6,136 patients enrolled in AIEOP-BFM ALL 2009, 2,514 patients (41.0%) were eligible for this random assignment, with 82.7% actually randomly assigned (EA: n = 1,040 and CA: n = 1,039).

在 AIEOP-BFM ALL 2009 研究中，共有 6,136 名患者入组，其中 2,514 名患者（占 41.0%）符合本项随机分组条件，实际随机分组率为 82.7%（CA 组：n = 1,040；EA 组：n = 1,039）。

The 5-year EFS was 92.5% (SE 0.8%) in CA and 92.2% (SE 0.9%) in EA.

在 CA 组中，5 年无事件生存（EFS）率为 92.5%（标准误 0.8%），而在 EA 组中为 92.2%（标准误 0.9%）。

Accordingly, cumulative incidenceof relapse was 5.8% (SE 0.7%) and 5.7% (SE 0.7%), and overall survivalwas 97.6% (SE 0.5%) and 97.4% (SE 0.5%) in CA and EA, respectively.

因此，CA和EA的复发累积发生率分别为5.8%（标准误0.7%）和5.7%（标准误0.7%），总生存率分别为97.6%（标准误0.5%）和97.4%（标准误0.5%）。

Life-threatening and fatal ARSI were similar in the two arms, but there was a three times lower incidenceof invasive fungal infections in the EA (0.5% v 1.5%, P = .02).

两组中威胁生命和致命的ARSI相似，但在EA中侵袭性真菌感染的发生率比对照组低三倍（0.5%对比1.5%，P = .02）。

Conclusions

A reduced DNR dose during induction did not compromise the outcome of patients with favorable prognostic factors but did diminish infectious toxicity indicated by the lower rate of invasive fungal infections.

在诱导治疗期间减少去甲肾上腺素剂量并未影响具有良好预后因素的患者的治疗结果，但降低了侵袭性真菌感染的发生率，表明感染性毒性有所减轻。