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СтатьяНазвание и аннотация: Перевод в очереди
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Huang Chenrong, Du Xiaohuan, Xue Ling, Song Lin, Liu Xiaoxue, Chen Zhiyao, Wang Xiaoling, Qin Maoquan, Sun Ximu, Wang Dao, Yang Jing, Li Dongjun, Jiang Hua, Ding Wenjiao, Qu Yuhua, Zhu Zengyan, Zhao Libo, Yuan Jinjie, Dong Ji, Wu Depei, Hu Shaoyan, Miao Liyan
Аннотация
PURPOSE: Therapeutic drug monitoring-based individualized busulfan (Bu) administration improves hematopoietic stem cell transplantation (HSCT) outcomes, but optimal Bu exposure in Chinese pediatric patients remains unclear; we aim to identify the optimal exposure level of Bu in such patients receiving Bu-based conditioning regimens of different intensities.
PATIENTS AND METHODS: Pediatric patients from 5 transplant centers in China who received Bu-based myeloablative conditioning regimens were included. Bu exposure, defined as the area under the concentration-time curve (AUC), was estimated using a population pharmacokinetic model, including the first-dose AUC and cumulative AUC (cAUC). The primary and secondary outcomes included event-free survival (EFS) and transplantation-related complications. Restricted cubic splines and Cox proportional hazards models were used to analyze the exposure‒response relationships between the Bu AUC and outcomes.
RESULTS: A total of 455 pediatric patients were enrolled, with 326 receiving a 3-day Bu-based (Bu3) regimen and 129 receiving a 4-day Bu-based (Bu4) regimen. Among all patients, a first-dose Bu AUC ≥ 4.5 mg×h/L was associated with a significantly higher 2-year EFS compared with AUC < 4.5 mg×h/L (84.6% vs 76.4%; P = 0.02). In the Bu3 cohort, a cAUC < 54 mg×h/L was associated with a lower 2-year EFS rate (77.7% vs 86.4%; P=0.04). In the Bu4 cohort, a cAUC of 70-90 mg×h/L was associated with a greater 2-year EFS rate (88.9%) than an exposure <70 mg×h/L (71.0%; P = 0.03) or >90 mg×h/L (66.1%; P = 0.04).
CONCLUSION: This study demonstrated an association between Bu exposure and EFS in Chinese pediatric HSCT patients, with optimal cumulative AUC values of ≥ 54 mg×h/L and 70-90 mg×h/L identified for the Bu3 and Bu4 regimens, respectively. Additionally, a first-dose Bu AUC ≥ 4.5 mg×h/L was associated with a favorable 2-year EFS.
PATIENTS AND METHODS: Pediatric patients from 5 transplant centers in China who received Bu-based myeloablative conditioning regimens were included. Bu exposure, defined as the area under the concentration-time curve (AUC), was estimated using a population pharmacokinetic model, including the first-dose AUC and cumulative AUC (cAUC). The primary and secondary outcomes included event-free survival (EFS) and transplantation-related complications. Restricted cubic splines and Cox proportional hazards models were used to analyze the exposure‒response relationships between the Bu AUC and outcomes.
RESULTS: A total of 455 pediatric patients were enrolled, with 326 receiving a 3-day Bu-based (Bu3) regimen and 129 receiving a 4-day Bu-based (Bu4) regimen. Among all patients, a first-dose Bu AUC ≥ 4.5 mg×h/L was associated with a significantly higher 2-year EFS compared with AUC < 4.5 mg×h/L (84.6% vs 76.4%; P = 0.02). In the Bu3 cohort, a cAUC < 54 mg×h/L was associated with a lower 2-year EFS rate (77.7% vs 86.4%; P=0.04). In the Bu4 cohort, a cAUC of 70-90 mg×h/L was associated with a greater 2-year EFS rate (88.9%) than an exposure <70 mg×h/L (71.0%; P = 0.03) or >90 mg×h/L (66.1%; P = 0.04).
CONCLUSION: This study demonstrated an association between Bu exposure and EFS in Chinese pediatric HSCT patients, with optimal cumulative AUC values of ≥ 54 mg×h/L and 70-90 mg×h/L identified for the Bu3 and Bu4 regimens, respectively. Additionally, a first-dose Bu AUC ≥ 4.5 mg×h/L was associated with a favorable 2-year EFS.