Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

作     者：Ya-qing SHEN Zhu-jun WANG Xiao-yan WU Kun LI Zhong-jian WANG Wen-fu XU Fen ZHOU Run-ming JIN Ya-qing SHEN;Zhu-jun WANG;Xiao-yan WU;Kun LI;Zhong-jian WANG;Wen-fu XU;Fen ZHOU;Run-ming JIN

作者机构：Department of PediatricsUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China 

出 版 物：《Current Medical Science》 (当代医学科学（英文）)

年 卷 期：2022年第42卷第4期

页      面：769-777页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100211[医学-妇产科学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.81700147 and No.82070172). 

主　　题：methotrexate high-dose methotrexate individualizing methotrexate dose toxicity acute lymphoblastic leukemia prognosis 

摘      要：Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.