Mungle Tushar, Mahadevan Ananya, Mukhopadhyay Jayanta, Bhattacharya Sangeeta Das, Saha Vaskar, Krishnan Shekhar
School of Medical Sciences and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, 721 302, India.
Tata Translational Cancer Research Centre, Tata Medical Center, Kolkata, West Bengal, 700 160, India.
JAMIA Open. 2024 Sep 13;7(3):ooae089. doi: 10.1093/jamiaopen/ooae089. eCollection 2024 Oct.
During the 2-year maintenance treatment phase (MT) of acute lymphoblastic leukemia (ALL), personalized patient-specified titration of oral antimetabolite drug doses is required to ensure maximum tolerated systemic drug exposure. Drug titration is difficult to implement in practice and insufficient systemic drug exposure resulting from inadequate dose titration increases risk of ALL relapse.
We developed an open-source R-based analytical toolkit, including the allMT R package and an interactive web-based R Shiny VIATAMIN application, to evaluate antimetabolite drug titration during MT.
Evaluation is initiated with basic visualization analysis of drug titration, in both individual patients and patient cohorts. Observations are supplemented with descriptive analyses of hematological toxicity frequency and prescriber compliance rates with protocol drug titration rules. In individual patients, visual and quantitative analyses indicate recurring potentially correctable suboptimal drug titration patterns. In patient cohorts, the toolkit enables evaluation of the impact of interventions to optimize MT drug titration.
Incorporation of the toolkit in a forthcoming clinical decision support system for MT would enable real-time examination and course correction of drug titration practice.
Future versions will be enhanced to include other variables that influence drug titration practice, including clinical toxicity data and later, pharmacological markers of antimetabolite, adherence, and drug activity.
在急性淋巴细胞白血病（ALL）的2年维持治疗阶段（MT），需要根据患者个体情况对口服抗代谢药物剂量进行个性化滴定，以确保达到最大耐受的全身药物暴露量。药物滴定在实际操作中很难实施，而剂量滴定不足导致的全身药物暴露不足会增加ALL复发的风险。
我们开发了一个基于R语言的开源分析工具包，包括allMT R包和基于网络的交互式R Shiny VIATAMIN应用程序，用于评估维持治疗期间抗代谢药物的滴定情况。
评估从对个体患者和患者队列的药物滴定进行基本可视化分析开始。通过对血液学毒性频率和处方者对方案药物滴定规则的依从率进行描述性分析来补充观察结果。在个体患者中，视觉和定量分析表明存在反复出现的、可能可纠正的次优药物滴定模式。在患者队列中，该工具包能够评估优化维持治疗药物滴定的干预措施的影响。
将该工具包纳入即将推出的维持治疗临床决策支持系统，将能够对药物滴定实践进行实时检查和纠正。
未来版本将进行改进，纳入其他影响药物滴定实践的变量，包括临床毒性数据，以及之后的抗代谢物、依从性和药物活性的药理学标志物。
