Abstract

Acute lymphoblastic leukaemia (ALL) is associated with a compromised myeloid system. Understanding the state of granulopoiesis in a patient during treatment, places the clinician in an advantageous position. Mathematical models are aids able to present the clinician with insight into the behaviour of myeloid-derived leucocytes. The main objective of this investigation was to determine whether a proposed model of ALL during induction therapy would be a usable descriptor of the system. The model assumes the co-occurrence of the independent leukaemic and normal marrow populations. It is comprised of four delay-differential equations, capturing the fundamental characteristics of the blood and bone marrow myeloid leucocytes and B-lineage lymphoblasts. The effect of treatment was presumed to amplify cell loss within both populations. Clinical data was used to inform the construction, calibration and examination of the model. The model is promising—presenting a good foundation for the development of a clinical supportive tool. The predicted parameters and forecasts aligned with clinical expectations. The starting assumptions were also found to be sound. A comparative investigation highlighted the differing responses of similarly diagnosed patients during treatment and further testing on patient data emphasized patient specificity. Model examination recommended the explicit consideration of the suppressive effects of treatment on the normal population production. Additionally, patient-related factors that could have resulted in such different responses between patients need to be considered. The parameter estimates require refinement to incorporate the action of treatment. Furthermore, the myeloid populations require separate consideration. Despite the model providing explanation, incorporating these recommendations would enhance both model usability and predictive capacity.

中文翻译：

---

用数据驱动的粒细胞-单核细胞-母细胞模型描述治疗后的 B 系小儿急性淋巴细胞白血病中髓源性白细胞的演变。

摘要

急性淋巴细胞白血病 (ALL) 与受损的骨髓系统有关。了解患者在治疗期间的粒细胞生成状态，可使临床医生处于有利地位。数学模型有助于让临床医生深入了解骨髓源性白细胞的行为。这项调查的主要目的是确定在诱导治疗期间提出的 ALL 模型是否是系统的可用描述符。该模型假设独立的白血病和正常骨髓群体同时发生。它由四个延迟微分方程组成，捕捉血液和骨髓髓系白细胞和 B 系淋巴母细胞的基本特征。假定治疗效果会放大两个群体中的细胞损失。临床数据用于为模型的构建、校准和检查提供信息。该模型很有前景——为开发临床支持工具奠定了良好的基础。预测参数和预测符合临床预期。开始的假设也被发现是合理的。一项比较研究强调了类似诊断的患者在治疗期间的不同反应，对患者数据的进一步测试强调了患者的特异性。模型检查建议明确考虑治疗对正常种群生产的抑制作用。此外，需要考虑可能导致患者之间出现这种不同反应的患者相关因素。参数估计需要细化以纳入治疗作用。此外，髓细胞群需要单独考虑。尽管模型提供了解释，但结合这些建议将增强模型的可用性和预测能力。