急性淋巴细胞白血病晚期骨髓复发并门冬酰胺酶静默失活1例

Case report of silent inactivation of Asparaginase in acute lymphoblastic leukemia with late bone marrow relapse

对2019年10月中山大学附属第一医院诊治的1例急性淋巴细胞白血病(ALL)患儿采用培门冬酶治疗后静默失活的临床资料进行回顾性分析。患儿,男,9岁3个月,ALL晚期骨髓复发,使用产自大肠杆菌的聚乙二醇修饰的培门冬酶化疗后因未出现预期的不良反应,如高血氨、低纤维蛋白原、低抗凝血酶Ⅲ(ATⅢ)等,进一步检测血浆门冬酰胺(ASN)浓度未达到耗竭标准,门冬酰胺酶活性为64.5 U/L,诊断为静默失活。更换为产自欧文菌的门冬酰胺酶治疗后,患儿ATⅢ最低降至33%,纤维蛋白原最低降至1.20 g/L,高血氨、ASN降低,门冬酰胺酶活性为1813.0 U/L,提示更换剂型治疗有效。临床医师应警惕门冬酰胺酶静默失活的发生,使用门冬酰胺酶治疗的患儿应监测门冬酰胺酶活性;在无条件检测酶活性的时候,密切监测有无高血氨、凝血功能紊乱等治疗相关不良反应对门冬酰胺酶静默失活有一定提示意义。

Retrospective analysis was performed on 1 child with silent inactivation(SI)of asparaginase(ASNas)who was diagnosed with acute lymphoblastic leukemia(ALL)and treated in the First Affiliated Hospital,Sun Yat-Sen University in October 2019.The patient was a 9 years and 3 months old boy who was diagnosed as ALL accompanied with late bone marrow relapse.After pegylated Escherichia coli-Asparaginase(PEG-ASNase)was given,he did not have the expected treatment-related adverse reactions,including hyperammonemia,hypofibrinogenemia,and the low activation of antithrombinⅢ(ATⅢ).The plasma asparagine(ASN)concentration failed to meet the depletion criteria and the ASNase activity was 64.5 U/L.Therefore,the SI of ASNase was confirmed.Erwinase was used to replace PEG-ASNase,the lowest level of ATⅢwas 33%,and the lowest level of fibrinogen was 1.20 g/L.Hyperammonemia and decreased ASN were also observed,and the ASNase activity was 1813.0 U/L.All the above suggested that when,SI occurred,the replacement by Erwinase was effective.The ASNase activity should be monitored in ALL patients who were treated with ASNase.Monitoring the treatment-related adverse reactions such as hyperammonia and coagulation disorders closely has important implications to the SI of ASNase when the detection of ASNase activity was unavailable.