门冬酰胺酶治疗成人和儿童急性淋巴细胞白血病时不良反应比较及处理

The adverse events and its management associated with asparaginase in the treatment of children and adult with acute lymphoblastic leukemia

目的:研究以门冬酰胺酶(ASP)为主的联合化疗方案治疗儿童和成人急性淋巴细胞白血病(ALL)/淋巴母细胞淋巴瘤(LBL)时的不良反应及处理。方法:25例儿童和45例成人ALL/LBL共接受118疗程含ASP的联合化疗方案治疗。监测治疗前后的凝血指标、肝功能、血脂和血糖。临床或血液检查怀疑胰腺炎时行超声或CT检查。怀疑血栓形成时进行相应血管超声检查。结果:ASP相关的临床不良反应包括过敏反应、静脉血栓和急性胰腺炎,发生率分别为1.7%、1.7%和2.5%。这些并发症均导致治疗中断或原计划的治疗方案推迟2周-3周。另有因脑出血致死亡一例。实验室检查肝功能异常、低纤维蛋白原血症、高甘油三酯血症和高血糖的发生率分别为38.99%、41.5%、5.6%和6.1%。比较儿童和成人各种不良反应的发生率和严重程度均无明显差别。结论:ASP治疗过程中可产生多种不良反应,少数可致死,需密切监测,早期采取措施进行干预。

Objective：To determine the incidence and clinical consequences of adverse events of asparaginase（ASP） in the treatment of children and adult with acute lymphoblastic leukemia（ALL）/lymphoblastic lymphoma（LBL） and explore its management.Methods： Twenty-five children aged 3.5-12 years and forty-five adults aged 13-62 years with ALL/LBL received 118 cycles of combination chemotherapy contained ASP.Coagulation screening test,liver function,cholesterol and triglycerides and blood glucose were measured in all patients before and during ASP treatment.CT or vessel ultrasound were used to confirm the diagnosis if suspected of venous thrombosis or acute pancreatitis.Results： The incidence of hypersensitivity,thromboembolism and pancreatitis were 1.7%,1.7% and 2.5%,respectively.These complications led to treatment interruptions and planned chemotherapy were delayed for 2-3 weeks.The incidence of laboratory abnormalities including liver dysfunction,hypofibrinogenemia（defined as less than 100mg/dl）,hypertriglyceridemia and hyperglycemia were 38.99%,41.5%,5.6% and 6.1%,respectively.One patient died of ASP-associated intracranial hemorrhage.No significant differences in incidence and severity of side effects were observed between children and adult.Conclusion： Close monitoring during ASP therapy for adverse effects will enable prompt recognition and early correction and prevent delay in therapy of ALL/LBL.