Acute lymphoblastic leukemia is the most common malignancy in childhood and requires prolonged oral maintenance chemotherapy to prevent disease relapse after remission induction with intensive intravenous chemotherapy. In maintenance therapy, drug doses of 6-mercaptopurine (6-MP) and methotrexate (MTX) are adjusted to achieve sustained antileukemic activity without excessive myelosuppression. However, uncertainty exists regarding timing and extent of drug dose responses and optimal dose adaptation strategies. We propose a novel comprehensive mathematical model for 6-MP and MTX pharmacokinetics, pharmacodynamics and myelosuppression in acute lymphoblastic maintenance therapy. We personalize and cross-validate the mathematical model using clinical data and propose a real-time algorithm to predict chemotherapy responses with a clinical decision support system as a potential future application.

中文翻译：

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儿童急性淋巴细胞白血病维持治疗期间白细胞动力学的数学模型。

急性淋巴细胞白血病是儿童期最常见的恶性肿瘤，需要长期口服维持化疗，以防止通过强化静脉化疗缓解后诱导疾病复发。在维持治疗中，调整6-巯基嘌呤（6-MP）和氨甲蝶呤（MTX）的药物剂量以实现持续的抗白血病作用，而不会过度抑制骨髓。但是，关于药物剂量反应的时间和范围以及最佳剂量适应策略存在不确定性。我们提出了6-MP和MTX在急性淋巴细胞维持治疗中的药代动力学，药效学和骨髓抑制的新型综合数学模型。