儿童急性淋巴细胞白血病应用门冬酰胺酶治疗的临床研究

Clinical study of treatment with asparaginase in pediatric acute lymphoblastic leukemia

目的回顾性总结和分析应用左旋门冬酰胺酶(L-Asp)治疗儿童急性淋巴细胞白血病(ALL)的经验、不良反应及其应对措施,以期对未来用药提供借鉴。方法 102例ALL患儿入组。分析超敏反应对疗效的影响,总结凝血功能异常及暂时性高血糖(TH)的应对措施,对L-Asp相关胰腺炎(AAP)病例作简要总结。结果(1)34例(33.3%)出现超敏反应,多数程度较轻且发生于诱导期以后的治疗过程中。(2)PT延长16例(20.3%),APTT延长17例(21.5%),FIB不同程度降低,50例(63.3%)低于1g/L,4例(5.I%)低于0.5g/L。(3)70例(68.6%)出现不同程度的血糖升高,11例(10.8%)诊断TH,其中4例(36.4%)有高血糖家族史。(4)4例(3.9%)发生AAP,1例再次应用L-Asp后未出现AAP。结论(1)超敏反应组和无超敏反应组的预计5年OS和EFS差异无显著性。(2)L-Asp治疗过程中出现的凝血功能改变原则上在无严重合并症时可不行预防性凝血因子的替代治疗。(3)高年龄组(≥6岁)及有糖尿病家族史者发生TH的可能性更大。(4)AAP发生后48 h内症状缓解、淀粉酶和脂肪酶低于正常值上限3倍以及影像学未提示假性囊肿或坏死者可尝试再次应用L-Asp化疗。

Objective This study was designed to provide guidance in medication by retrospective summary and analysis of experience in treatment with L-Asparaginase （L-Asp） and management of side effects. Methods 102 ALL patients were enrolled. Retrospective summary was undertaken to analyze the impact of hypersensitivity on the efficacy of ALL chemotherapy, to summarize the management of thrombotic complications and transient hyperglycemia （TH） , and to illustrate cases with asparaginase associated pancreatitis （AAP）. Results （ 1 ） 34 patients （ 33. 3% ） had experienced asparaginase hypersensitivities, most of which were mild and occurred in phases after induction. （2） Prolonged PT and APTT were reported in 16 （20.3%） and 17 （21.5%） cases respectively, with hypofibrinogenemia in various degree,of which 50 （63.3%） below 1g/L and 4 （5.1%） below 0.5g/L. （3） 70 patients （68.6%） were detected with high blood glucose in various degrees, 11 cases were diagnosed as TH, of which 4 patients （36.4%） with family history of diabetes. （4） 4 patients（3.9% ）have developed AAP, of which one was re-introduced to L-Asp without another episode of AAP. Conclusions （ 1 ） Patients who developed hypersensitivity exhibit no significant difference in OS and EFS. （2） Preventative infusions of clotting factors for changes in coagulation are not necessary unless suffered severe complications. （3） Patients over age 6 or with family history of diabetes were more likely to have TH. （4） We recommend that L-asp could be re-introduced to patients who have no AAP symptoms within 48 h, whose amylase and lipase levels below three times of the upper normal limit, and no pseudocysts or necrosis on imaging.