Determination of l-Asparaginase Activity and Its Therapeutic Monitoring in Children with Hematological Malignancies in a Single Croatian Center

Diagnostics (Basel). 2024 Mar 15;14(6):623. doi: 10.3390/diagnostics14060623.

Abstract

Background: Among malignant diseases which develop during childhood, hematological cancers, such as leukemias and lymphomas, are the most common. Outcomes have greatly improved due to the refinement of multiagent chemotherapy regimens that include enhanced asparaginase therapy. In this study, we aimed to evaluate our experiences related to the analytical and clinical significance of determining l-Asparaginase activity.

Methods: Since 2016, the Laboratory of the Children's Hospital Zagreb has routinely measured l-Asparaginase activity and to date, has measured more than 280 examples of activity in a total of 57 children with hematological malignancy treated at the Pediatric Oncology Department of the Children's Hospital Zagreb. Three asparaginase products were available: native E. colil-Asparaginase; a pegylated form of this enzyme; and a native product from Erwinia chrysanthemi. A retrospective data analysis was performed.

Results: Out of the fifty-seven children, seven had an allergic reaction (12.3%), five (8.8%) had silent inactivation, and seven (12.3%) developed acute pancreatitis. Allergic reactions and silent inactivation were more common in children treated with native E. colil-Asparaginase, while pancreatitis was more common in children treated with the pegylated form.

Conclusions: The monitoring of l-Asparaginase activity may help to optimize therapy by identifying patients with 'silent inactivation', and/or by dose correction when l-Asparaginase activity is too high (slow elimination).

Keywords: asparaginase; asparaginase enzyme activity; child; lymphoblastic malignancy; therapeutic drug monitoring.

Grants and funding

Eurotron International doo provided funding to Jasna Lenice Krleza for a training course on the measurement of l-Asparaginase activity in the Pediatric Oncology Laboratory of Sophia Children’s Hospital (Erasmus Medical Center, Rotterdam, The Netherlands) and received funding for the training course from Jazz Pharmaceuticals in the form of donations (educational scholarship approved on 5 June 2015. and disbursed on 17 November 2015. after completion of the course, Registry number: 014-28/70-15). This research received no other external funding.