【摘要】 背景与目的:门冬酰胺酶是目前治疗儿童淋巴系统肿瘤的重要组成药物,但左旋门冬酰胺酶(l-asparaginase,L-Asp)的不良反应较多,培门冬酶(pegasparaginase,PEG-Asp)是近年国内新上市的门冬酰胺酶制剂。本研究观察PEG-Asp在儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)和(或)淋巴母细胞性淋巴瘤(lymphoblastic lymphoma,LBL)中作为一线应用药物的疗效,并对其安全性进行评价。方法:2008年4月—2013年3月复旦大学附属儿科医院血液科住院使用门冬酰胺酶治疗的ALL和LBL患儿共211例,其中PEG-Asp一线治疗患儿42例,非PEG-Asp一线治疗组169例(包括L-Asp一线治疗组116例,诱导期使用L-Asp、巩固期使用PEG-Asp组53例)。分析CCLG 2008及NHL-BFM 90方案使用期间PEG-Asp一线治疗组和非PEGAsp一线治疗组儿童ALL和(或)LBL的临床疗效、不良反应发生率的差异。结果:42例PEG-Asp一线治疗患儿中ALL 35例,治疗1个疗程诱导缓解后完全缓解率为97.1%,其中高危ALL为83.3%;LBL 7例,无Ⅰ、Ⅱ期患儿,Ⅲ、Ⅳ期患儿经1个疗程完全治疗缓解率为57.1%。与诱导期使用L-Asp治疗组患儿比较,1个疗程完全缓解率差异无统计学意义(P>0.05)。复发患儿34例,PEG-Asp一线治疗组5例;以L-Asp作为一线治疗组16例;诱导期使用L-Asp,巩固及强化期使用PEG-Asp组13例。死亡31例,3组分别为3例、18例、10例。死于复发22例,疾病未缓解死亡4例,因并发症死亡5例。PEG-Asp一线治疗组和非PEG-Asp一线治疗组之间复发率和死亡率差异无统计学意义(P>0.05)。门冬酰胺酶相关不良反应127例,PEG-Asp一线治疗组发生不良反应事件20例,发生率为47.6%,非PEG-Asp一线治疗组发生不良反应107例,发生率为63.3%,主要不良反应为过敏反应、肝功能异常、凝血功能异常、消化道反应、高血糖和胰腺炎。除过敏反应发生率PEG-Asp一线治疗组低于非PEG-Asp组外(P=0.03),两组间其他不良反应差异无统计学意义(P>0.05)。结论:ALL和(或)LBL患儿中以PEG-Asp替代L-Asp作为一线治疗近期疗效满意,过敏反应发生率低,治疗时仍需监测与干预不良反应。更多还原

【Abstract】 Background and purpose: L-asparaginase(L-Asp) is an important drug in the treatment of childhood lymphoid neoplasms at present, but a lot of adverse reactions of L-Asp were observed. Pegasparaginase(PEG-Asp) is available in China in recent years. This study aimed to explore effi cacy and side-effect of PEG-Asp as fi rst-line treatment in childhood acute lymphoblastic leukemia(ALL) and lymphoblastic lymphoma(LBL). Methods: A total number of 211 ALL or LBL patients were treated with CCLG 2008 or BFM-90 protocol with PEG-Asp or L-Asp between Apr. 2008 and Mar. 2013; 42 patients, among whom, were 35 ALL patients and 7 LBL patients, were treated with PEG-Asp as fi rst-line treatment; 169 patients were treated with L-Asp as fi rst-line treatment(including 53 patients treated with L-Asp during induction protocol; with PEG-Asp during consolidate protocol). The clinical outcome and adverse reaction of PEG-Asp with L-Asp were observe and compared. Results: There were 35 ALL patients in PEG-Asp fi rst-line treatment group and the complete remission rate after 1 course of PEG-Asp was 97.1%,however, which was 83.3% of high risk ALL patients. The complete remission rate of 7 LBL patients of PEG-Asp fi rstline treatment group was 57.1%. There was no signifi cant difference between 2 groups(P>0.05). Thirty-four patients relapsed including 5 patients of PEG-Asp fi rst-line treatment group, 16 patients of L-Asp fi rst-line treatment group and 13 patients treated with L-Asp during induction protocol and with PEG-Asp during consolidate protocol. Thirty-one patients died including 3, 18, 10 patients in 3 groups respectively. Twenty-two patients died of relapse, 4 died without remission, 5 died of complications. There was also no signifi cant difference between 2 groups(P>0.05). The incidence rates of adverse reactions were 47.6% and 63.3% respectively. Anaphylaxis, liver functions abnormalities, blood coagulation abnormalities, gastrointestinal reaction, hyperglycemia and pancreatitis were common in our patients. The incidence rate of anaphylaxis in PEG-Asp as fi rst-line treatment group was lower than other groups(P=0.03). But there was no signifi cant difference been observed in the incidence of other adverse reaction. Conclusion: The short-term effi cacy of PEG-Asp as the fi rst-line treatment in childhood leukemia and lymphoma was satisfactory and the incidence rate of anaphylaxis was lower. However, we will still pay much attention to adverse reaction monitoring of PEG-Asp.更多还原