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Characterizing Chemotherapy-Induced Neutropenia and Monocytopenia Through Mathematical Modelling
Bulletin of Mathematical Biology ( IF 2.0 ) Pub Date : 2020-07-31 , DOI: 10.1007/s11538-020-00777-0
Tyler Cassidy 1 , Antony R Humphries 2, 3 , Morgan Craig 4, 5 , Michael C Mackey 6, 7, 8
Affiliation  

In spite of the recent focus on the development of novel targeted drugs to treat cancer, cytotoxic chemotherapy remains the standard treatment for the vast majority of patients. Unfortunately, chemotherapy is associated with high hematopoietic toxicity that may limit its efficacy. We have previously established potential strategies to mitigate chemotherapy-induced neutropenia (a lack of circulating neutrophils) using a mechanistic model of granulopoiesis to predict the interactions defining the neutrophil response to chemotherapy and to define optimal strategies for concurrent chemotherapy/prophylactic granulocyte colony-stimulating factor (G-CSF). Here, we extend our analyses to include monocyte production by constructing and parameterizing a model of monocytopoiesis. Using data for neutrophil and monocyte concentrations during chemotherapy in a large cohort of childhood acute lymphoblastic leukemia patients, we leveraged our model to determine the relationship between the monocyte and neutrophil nadirs during cyclic chemotherapy. We show that monocytopenia precedes neutropenia by 3 days, and rationalize the use of G-CSF during chemotherapy by establishing that the onset of monocytopenia can be used as a clinical marker for G-CSF dosing post-chemotherapy. This work therefore has important clinical applications as a comprehensive approach to understanding the relationship between monocyte and neutrophils after cyclic chemotherapy with or without G-CSF support.

中文翻译:

通过数学建模表征化疗引起的中性粒细胞减少症和单核细胞减少症

尽管最近专注于开发治疗癌症的新型靶向药物,但细胞毒性化疗仍然是绝大多数患者的标准治疗方法。不幸的是,化疗与高造血毒性有关,可能会限制其疗效。我们之前已经建立了减轻化疗引起的中性粒细胞减少症(缺乏循环中性粒细胞)的潜在策略,使用粒细胞生成的机械模型来预测定义中性粒细胞对化疗反应的相互作用,并定义同步化疗/预防性粒细胞集落刺激因子的最佳策略(G-CSF)。在这里,我们通过构建和参数化单核细胞生成模型将我们的分析扩展到包括单核细胞的产生。使用大量儿童急性淋巴细胞白血病患者化疗期间中性粒细胞和单核细胞浓度的数据,我们利用我们的模型来确定循环化疗期间单核细胞和中性粒细胞最低点之间的关系。我们表明单核细胞减少症先于中性粒细胞减少症 3 天,并通过确定单核细胞减少症的发作可用作化疗后 G-CSF 给药的临床标志物来合理化化疗期间 G-CSF 的使用。因此,这项工作作为一种综合方法具有重要的临床应用,可用于了解有或没有 G-CSF 支持的循环化疗后单核细胞和中性粒细胞之间的关系。我们利用我们的模型来确定循环化疗期间单核细胞和中性粒细胞最低点之间的关系。我们表明,单核细胞减少症先于中性粒细胞减少症 3 天,并通过确定单核细胞减少症的发作可用作化疗后 G-CSF 给药的临床标志物来合理化化疗期间 G-CSF 的使用。因此,这项工作具有重要的临床应用,作为了解有或没有 G-CSF 支持的循环化疗后单核细胞和中性粒细胞之间关系的综合方法。我们利用我们的模型来确定循环化疗期间单核细胞和中性粒细胞最低点之间的关系。我们表明,单核细胞减少症先于中性粒细胞减少症 3 天,并通过确定单核细胞减少症的发作可用作化疗后 G-CSF 给药的临床标志物来合理化化疗期间 G-CSF 的使用。因此,这项工作具有重要的临床应用,作为了解有或没有 G-CSF 支持的循环化疗后单核细胞和中性粒细胞之间关系的综合方法。
更新日期:2020-07-31
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