儿童急性髓系白血病的生存率仍然较低，尽管已经实施了最大化的造血抑制治疗。用于治疗肺孢子菌性肺炎的阿托伐醌（AQ）可以抑制氧化磷酸化（OXPHOS），并减轻移植小鼠模型中髓系白血病负担，成为一种理想的同时治疗方法。但由于口感差和产品形式限制，AQ在儿童急性髓系白血病患者中的使用十分有限。研究在两家医院招募了新诊断的AML患者。在Medical Research Council骨架指导下，每日使用已确定的预防肺孢子菌性肺炎剂量的AQ与标准的AML治疗相结合。收集了Induction 1期间的AQ服从度、不良事件、使用难易度评分（标尺：1（非常困难）-5（非常容易））和血/骨髓药代动力学数据。相关研究评估了AQ引起的细胞凋亡和对OXPHOS的影响。移植小鼠模型通过AQ治疗。总共有26名患者参与入组（年龄为7.2个月至19.7岁，中位数为12岁），其中24位可评估。总共14名（58％）和19名（79％）可评估患者在第11天和诱导治疗结束时，血浆中达到已知的抗白血病浓度（＞10 µM）。7位（29％）患者达到了预防肺孢子菌性肺炎所需的足够浓度（＞40 µM）。平均使用难易度评分为3.8。在患者样本中使用AQ的相关研究显示了强大的细胞凋亡、OXPHOS抑制和移植小鼠模型中的延长生存时间。将AQ与化疗结合治疗AML在Induction 1期间在儿童患者中似乎是可行和安全的，且在移植小鼠模型中表现出了单一药物的抗白血病效果。 AQ看起来是一种理想的同时治疗方法，但可能需要针对患者进行剂量调整，以达到足够预防肺孢子菌性肺炎的浓度。

Survival of pediatric AML remains poor despite maximized myelosuppressive therapy. The pneumocystis jiroveci pneumonia (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited product formulations have historically limited routine use of AQ in pediatric AML patients. Patients with de novo AML were enrolled at two hospitals. Daily AQ at established PJP dosing was combined with standard AML therapy, based on the Medical Research Council backbone. AQ compliance, adverse events (AEs), ease of administration score (scale: 1 (very difficult)-5 (very easy)) and blood/marrow pharmacokinetics (PK) were collected during Induction 1. Correlative studies assessed AQ-induced apoptosis and effects on OXPHOS. PDX models were treated with AQ. A total of 26 patients enrolled (ages 7.2 months-19.7 years, median 12 years); 24 were evaluable. A total of 14 (58%) and 19 (79%) evaluable patients achieved plasma concentrations above the known anti-leukemia concentration (>10 µM) by day 11 and at the end of Induction, respectively. Seven (29%) patients achieved adequate concentrations for PJP prophylaxis (>40 µM). Mean ease of administration score was 3.8. Correlative studies with AQ in patient samples demonstrated robust apoptosis, OXPHOS suppression, and prolonged survival in PDX models. Combining AQ with chemotherapy for AML appears feasible and safe in pediatric patients during Induction 1 and shows single-agent anti-leukemic effects in PDX models. AQ appears to be an ideal concomitant AML therapeutic but may require intra-patient dose adjustment to achieve concentrations sufficient for PJP prophylaxis.