Asparaginase (ASNase) is an important anti‐leukaemic drug in the treatment of childhood acute lymphoblastic leukaemia (ALL) and non‐Hodgkin lymphoma (NHL). A substantial proportion of patients develop hypersensitivity reactions with anti‐ASNase neutralising antibodies, resulting in allergic reactions or silent inactivation (SI), and characterised by inactivation and rapid clearance of ASNase. We report results of a prospective, real‐time therapeutic drug monitoring of pegylated Escherichia coli (PEG‐)ASNase and Erwinia ASNase in children treated for ALL and NHL in Belgium. Erwinia ASNase was given as second‐line after hypersensitivity to PEG‐ASNase. In total, 286 children were enrolled in the PEG‐ASNase cohort. Allergy was seen in 11·2% and SI in 5·2% of patients. Of the 42 patients treated with Erwinia ASNase, 7·1% experienced allergy and 2·4% SI. The median trough PEG‐ASNase activity was high in all patients without hypersensitivity. After Erwinia administration significantly more day 3 samples had activities <100 IU/l (62·5% vs. 10% at day 2 (D2)). The median D2 activity was significantly higher for intramuscular (IM; 347 IU/l) than for intravenous Erwinia administrations (159 IU/l). This prospective, multicentre study shows that monitoring of ASNase activity during treatment of children with ALL and NHL is feasible and informative. Treatment with Erwinia ASNase warrants close monitoring and optimally adherence to a 2‐day interval of IM administrations.

中文翻译：

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在比利时，对儿童的急性淋巴细胞白血病和非霍奇金淋巴瘤中的聚乙二醇化大肠杆菌和欧文氏门冬酰胺酶治疗进行前瞻性，实时监控。

天冬酰胺酶（ASNase）是一种重要的抗白血病药物，可治疗儿童急性淋巴细胞白血病（ALL）和非霍奇金淋巴瘤（NHL）。很大一部分患者会产生抗ASNase中和抗体的超敏反应，导致过敏反应或沉默失活（SI），并以ASNase失活和快速清除为特征。我们报告了在比利时接受ALL和NHL治疗的儿童中，对聚乙二醇化Escherichia coli（PEG-）ASNase和Erwinia ASNase进行前瞻性，实时治疗药物监测的结果。欧文尼亚ASNase是对PEG-ASNase过敏后的二线药物。共有286名儿童参加了PEG-ASNase研究。在11·2％的患者中观察到过敏，在5·2％的患者中观察到SI。在接受Erwinia ASNase治疗的42例患者中，有7·1％经历过过敏，而2·4％SI出现过。在没有超敏反应的所有患者中，中值谷氨酸PEG-ASNase活性较高。施用欧文氏菌后，第3天的活性明显低于100 IU / l（62·5％，而第2天（D2）为10％）。肌肉注射（IM; 347 IU / l）的中位D2活性明显高于静脉注射欧文氏菌管理（159 IU / l）。这项前瞻性，多中心研究表明，在ALL和NHL儿童治疗期间监测ASNase活性是可行且有益的。Erwinia ASNase的治疗可确保密切监测并最佳遵守IM给药间隔2天。