儿童门冬酰胺酶相关胰腺炎的临床特点及风险因素分析

Analysis in clinical characteristics and risk factors of asparaginase-associated pancreatitis in children

目的 分析接受培门冬酶(PEG-ASP)治疗的急性淋巴细胞白血病(ALL)患儿门冬酰胺酶相关胰腺炎(AAP)的临床特点及风险因素。方法 回顾性分析2016年3月—2020年3月在苏州大学附属儿童医院接受PEG-ASP治疗的810例ALL患儿的临床资料,分析AAP的临床特点、生化指标、治疗措施、预后及相关风险因素。结果 AAP发生率为4.8%(39/810)。AAP与性别、ALL免疫分型及危险分层无相关性,但年龄>10岁患儿的AAP发生率较≤10岁者升高,差异有统计学意义(P<0.01)。71.8%的AAP发生在首次或第2次接受PEG-ASP治疗期间,AAP发生的中位时间为PEG-ASP暴露后12 d,PEG-ASP的中位累积剂量为3 660 IU/m^(2)。92.3%的AAP患儿出现腹痛症状;94.9%的AAP患儿伴随血清淀粉酶或脂肪酶水平超过正常值上限3倍以上;89.5%的AAP患儿的影像学检查显示出胰腺炎迹象。39例AAP患儿经治疗后均好转,8例AAP患儿治愈后复用门冬酰胺酶(ASP)相关制剂,其中3例再次出现AAP。结论 年龄可能是AAP发生的风险因素之一,首次与第2次接受PEG-ASP治疗期间是AAP高发时间段。部分AAP患儿缺乏胰腺炎特征性临床症状,AAP患儿再次应用ASP相关制剂时仍有较高的复发风险。

Objective To analyze the clinical characteristics and risk factors of asparaginase-associated pancreatitis(AAP) in acute lymphoblastic leukemia(ALL) children treated by pegaspargase(PEG-ASP). Methods The clinical data of 810 ALL children treated by PEG-ASP from March 2016 to March 2020 in the Children’s Hospital Affiliated to Soochow University were analyzed retrospectively,and the clinical characteristics,biochemical indexes,therapeutic measures,prognosis and related risk factors of AAP were analyzed. Results The incidence of AAP was 4.8%(39/810). There were no significant correlations of AAP with gender,immune typing and risk stratification of ALL,but the incidence of AAP increased significantly in children aged over 10 years than those aged ≤10 years(P<0.01). 71.8% of AAP occurred during the first or second treatment in children with PEG-ASP,the median time of occurrence of AAP was 12 days after PEG-ASP exposure,and the median cumulative dose of PEG-ASP was 3 660 IU/m^(2).92.3% of AAP children had abdominal pain;94. 9% of AAP children had increase of serum amylase or lipase more than three times of the upper limit of normal value;imaging examination showed signs of pancreatitis in 89. 5% of children with AAP. A total of 39 children with AAP were improved after treatment,8 children with AAP were cured and reused ASP related preparations,of which 3 cases had AAP again. Conclusion Age may be one of the risk factors of AAP,and the first and second acceptance of PEG-ASP are the high incidence periods of AAP during treatment. Some AAP patients lack the characteristic clinical symptoms of pancreatitis,and AAP patients still have a high risk of recurrence when using ASP related preparations again.