Refining busulfan exposure enhances pediatric ALL HSCT outcomes: insights from the International FORUM study.

We identify this window for patients receiving busulfan within the prospective international, randomized controlled phase 3 ALLSCTped 2012 FORUM trial. We included 145 participants receiving fludarabine-busulfan-thiotepa conditioning, with available busulfan plasma levels.

我们在前瞻性国际、随机对照的第3阶段ALLSCTped 2012 FORUM试验中确定了这一窗口，该试验针对接受白消安治疗的患者。我们纳入了145名接受氟达拉滨-白消安-噻替派预处理方案的参与者，这些参与者的白消安血浆水平是可获得的。

Busulfan exposure was estimated using a validated pediatric population pharmacokinetic model.

Busulfan的暴露量是通过一个经过验证的儿科群体药代动力学模型来估计的。

Primary outcomes were event-free survival (EFS) and graft-versus-host disease-free relapse-free survival (GRFS).

主要结果是无事件生存（EFS）和无移植物抗宿主病的复发无生存（GRFS）。

Patients were aged between 0.5 and 19.5 years, with a median follow-up of 5.0 years.

患者年龄在0.5至19.5岁之间，中位随访时间为5.0年。

The optimal busulfan exposure was defined as area under busulfan concentration curve (cAUC) of 73.3 to 98.0 mg.h/L based on EFS and GRFS.

基于无事件生存（EFS）和基因重组无事件生存（GRFS），将最佳的白消安暴露定义为白消安浓度曲线下面积（cAUC）在73.3至98.0 mg.h/L之间。

Patients with nonoptimal exposure had lower EFS (hazard ratio[HR], 1.93; p = 0.008) and GRFS (HR, 2.01; p = 0.002).

非理想暴露的患者总生存期（EFS）较低（风险比[HR]，1.93；p = 0.008）和无复发生存期（GRFS）也较低（HR，2.01；p = 0.002）。

Underexposure (cAUC <73.3 mg.h/L) was associated with higher relapse rates (HR, 1.93; p = 0.019), and overexposure (cAUC >98.0 mg.h/L) with an increased risk of treatment-related toxicities and graft-versus-host disease.

暴露不足（cAUC <73.3 mg.h/L）与较高的复发率相关（HR, 1.93；p = 0.019），而过度暴露（cAUC >98.0 mg.h/L）则与治疗相关毒性增加和移植物抗宿主病的风险增加有关。

Patients with optimal busulfan exposure showed no differences in EFS, GRFS, overall survival, or relapse with post hoc matched total-body irradiation (TBI) recipients (n = 51 in each group).

在接受全身照射(TBI)的匹配受体(n=51)后，具有最佳布沙芬暴露量的患者在无事件生存(EFS)、无进展生存(GRFS)、总生存或复发方面没有差异。

This study identifies a favorable busulfan exposure window for pediatric patients with ALL undergoing HSCT from an HLA-matched donor.

该研究确定了接受HLA匹配供体造血干细胞移植(HSCT)的儿童ALL患者中布沙芬暴露的有利窗口期。

Therapeutic drug monitoring for optimized personalized busulfan dosing improves HSCT outcomes and might be validated for use as an alternative to irradiation.

通过优化个体化白消安剂量的治疗药物监测改善造血干细胞移植（HSCT）的临床结果，并可能作为替代放疗的验证方法。

This trial was registered at EudraCT as 2012-003032-22 and on www.ClinicalTrials.gov as NCT01949129.

该试验已在EudraCT注册为2012-003032-22，并在www.ClinicalTrials.gov上注册为NCT01949129。