培门冬酶与左旋门冬酰胺酶在儿童急性淋巴细胞白血病临床应用中的不良反应及防治

Adverse reactions of Pegaspargase and L-asparaginase in the clinical trement of childhood acute lymphoblastic leu-kemia

目的：比较培门冬酶（PEG-Asp）与左旋门冬酰胺酶（L-Asp）在儿童急性淋巴细胞白血病（ALL）临床应用中的不良反应及干预措施。方法回顾性分析2011年5月至2014年10月郑州大学第一附属医院56例曾应用 PEG-Asp 的 ALL 患儿的临床资料，其中50例为应用 PEG-Asp 前曾应用 L-Asp。56例患儿共应用 PEG-Asp 122个疗程，L-Asp 94个疗程。使用 PEG-Asp 和 L-Asp 前后1周内监测血常规、肝肾功能、凝血功能、淀粉酶、血糖、心电图及腹部彩超等相关指标，使用过程中严密观察患儿临床表现，比较两种药物的不良反应及干预措施。结果两种疗程均有不良反应出现，包括：过敏反应（PEG-Asp 0.8%，L-Asp 13.8%，P〈0.001），丙氨酸氨基转移酶（ALT）和（或）天门冬氨酸氨基转移酶（ AST）明显升高（5.7%、15.9%，P =0.014），白蛋白下降（9.8%，10.6%，P =0.847），纤维蛋白原（FIB）下降（39.3%，63.8%，P =0.001），活化部分凝血活酶时间（APTT）延长（26.2%，40.4%， P =0.027），血糖升高（2.4%，1.1%，P =0.451），严重消化道反应（3.3%，8.5%，P =0.096），血象下降需要多次输血（7.4%，18.1%，P =0.016），合并严重感染（6.6%，9.5%，P =0.414）。出现不良反应均及时给予对症处理，无一例患儿因出现不良反应死亡。结论 PEG-Asp 与 L-Asp 在治疗儿童急性淋巴细胞白血病中存在类似不良反应，但PEG-Asp 过敏反应发生率较 L-Asp 显著降低，肝功能损伤严重程度、凝血异常及血象下降程度均较 L-Asp 轻，可作为 L-Asp 替代治疗。

Objective To compare the adverse interventions reactions of Pegaspargase（PEG-Asp）and L-asparagi-nase（L-Asp）in the clinical treatment of childhood acute lymphoblastic leukemia（ALL）. Methods From May 2011 to October 2014,the clinical data of PEG-Asp in 56 children with ALL were analyzed retrospectively,including 50 children for previous application of L-Asp. The 56 children had 122 courses chemotherapy of PEG-Asp,94 courses of L-Asp. Laborato-ry tests,including routine blood,liver and kindey functions,coagulation funtion,serum amylase,blood glucose,electro-cardiogram and abdominal ultrasonography and other related indicators before and 1 week after chemotherapy were moni-tored,and the clinical manifestations were observed closely,the adverse reactions of PEG-Asp and L-Asp were compared. Results The adverse reactions of two courses including：allergic reaction（PEG-Asp 0. 8% ,L-Asp 13. 8% ,P〈 0. 01）, increased transaminase（5. 7% ,15. 9% ,P = 0. 014）,decreased albumin（9. 8% ,10. 6% ,P = 0. 847）,decreased fi-brinogen（39. 3% ,63. 8% ,P = 0. 001）,prolonged APTT（26. 2% ,40. 4% ,P = 0. 027）,hyperglycemia（2. 4% , 1. 1% ,P = 0. 451）,gastrointestinal reactions（3. 3% ,8. 5% ,P = 0. 096）,decreased blood transfusion（7. 4% , 18. 1% ,P = 0. 016）,with severe infection（6. 6% ,9. 5% ,P = 0. 414）. Adverse reactions were promptly given symp-tomatic treatment,no child died due to adverse reaction. Conclusions PEG-Asp shows similar adverse reactions as L-Asp in the treatment of children with ALL. However,the incidence of allergic reactions of PEG-Asp is lower than L-Asp signifi-cantly,the severity of liver dysfunction,blood clotting abnormalities and the degree of decline compared with L-Asp re-duced,so PEG-Asp can be another option for children with ALL.