Predicting busulfan exposure in patients undergoing hematopoietic stem cell transplantation using machine learning techniques

This study aimed to establish an optimal model to predict the busulfan (BU) area under the curve at steady state (AUCss) by using machine learning (ML).Seventy-nine adult patients (age ≥18 years) who received BU intravenously and underwent therapeutic drug monitoring from 2013 to 2021 at Fujian Medical University Union Hospital were enrolled in this retrospective study. The whole dataset was divided into a training group and test group at the ratio of 8:2. BU AUCss were considered as the target variable. Nine different ML algorithms and one population pharmacokinetic (pop PK) model were developed and validated, and their predictive performance was compared.All ML models were superior to the pop PK model (R2 = 0.751, MSE = 0.722, 14 and RMSE = 0.830) in model fitting and had better predictive accuracy. The ML model of BU AUCss established through support vector regression (SVR) and gradient boosted regression trees (GBRT) had the best predictive ability (R2 = 0.953 and 0.953, MSE = 0.323 and 0.326, and RMSE = 0.423 and 0.425).All the ML models can potentially be used to estimate BU AUCss with the aim of facilitating rational use of BU on the individualized level, especially models built by SVR and GBRT algorithms.