Case report of silent inactivation of Asparaginase in acute lymphoblastic leukemia with late bone marrow relapse / 中华实用儿科临床杂志

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 antithrombin Ⅲ (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 ATⅢ was 33%, and the lowest level of fibrinogen was 1.20 g/L.Hyperammonemia and decreased ASN were also observed, and the ASNase activity was 1 813.0 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.

Asparaginase: an old drug with new questions

ABSTRACT The long-term outcome of acute lymphoblastic leukemia has improved dramatically due to the development of more effective treatment strategies. L-asparaginase (ASNase) is one of the main drugs used and causes death of leukemic cells by systematically depleting the non-essential amino acid asparagine. Three main types of ASNase have been used so far: native ASNase derived from Escherichia coli, an enzyme isolated from Erwinia chrysanthemi and a pegylated form of the native E. coli ASNase, the ASNase PEG. Hypersensitivity reactions are the main complication related to this drug. Although clinical allergies may be important, a major concern is that antibodies produced in response to ASNase may cause rapid inactivation of ASNase, leading to a worse prognosis. This reaction is commonly referred to as "silent hypersensitivity" or "silent inactivation". We are able to analyze hypersensitivity and inactivation processes by the measurement of the ASNase activity. The ability to individualize the ASNase therapy in patients, adjusting the dose or switching patients with silent inactivation to an alternate ASNase preparation may help improve outcomes in those patients. This review article aims to describe the pathophysiology of the inactivation process, how to diagnose it and finally how to manage it.