Abstract:L-asparaginase (L-ASNase) is an enzyme that shows targeted activity against Acute Lymphoblastic Leukemia (ALL) and similar lymphoid neoplasms by facilitating the breakdown of asparagine into L-aspartic acid, thereby reducing L-asparagine levels in leukemic cells. However, its therapeutic potential is hindered by its associated toxicity, leading to complications, such as thrombosis, hemorrhage, thrombocytopenia, fibrinolysis, hypersensitivity reactions, and the development of Posterior Reversible Encephalopathy Syndrome (PRES). This review compiles documented cases of PRES linked to treating B and T cell acute lymphoblastic leukemia in children using L-ASNase. Although this pathology is rare, understanding its management is crucial within ASNase-based chemotherapy protocols. As PRES lacks a specific treatment, focusing on symptomatic management becomes pivotal. Therefore, comprehending the underlying causes during L-ASNase treatment for acute lymphoblastic leukemia is essential. Understanding the etiology and clinical symptoms of this illness is critical for early diagnosis and treatment. The cases of PRES described in this review include instances in which this syndrome has appeared after the administration of L-ASNase in children. In some cases, PRES developed during induction therapy, while in others, it occurred during the reinduction phase. These cases resolved days after discontinuation of L-ASNase. The findings suggest a close relationship between drug administration and the appearance of brain lesions, as evidenced by the disappearance or decrease of these lesions when the drug was eliminated from the bloodstream.

American Journal of Translational Research

Comparison of efficacy and safety of different asparaginases in adult acute lymphoblastic leukemia based on nano-magnetic beads immunoassay

Article

Author: Huang, Xiaoshan

OBJECTIVETo compare the efficacy and safety of different asparaginase formulations in the treatment of acute lymphoblastic leukemia (ALL) based on nano-magnetic bead immunoassay.METHODSRetrospective analysis of adult ALL patients' clinical data who admitted to The Affiliated Hospital of Changsha Health Vocational College from August 2020 to August 2023. Finally, 65 adult ALL patients were included in this study, including the polyethylene glycol conjugated asparaginase (PEG-ASNase) group (n = 32) and the L-asparaginase (L-ASNase) group (n = 33). Enzyme-linked immunosorbent assay (ELISA) based on magnetic nanoparticles was used to determine the activity of ASNase in both groups. The levels of asparagine or glutamine in two groups were detected by automatic biochemical analyzer during induction therapy, and the adverse events of the two groups were observed during the treatment.RESULTSPEG-ASNase demonstrated a slower decrease in enzyme activity, longer action duration, and higher safety profile compared to L-ASNase. PEG-ASNase group and L-ASNase group demonstrated a similar complete remission rate (71.88% vs. 60.61%). Event-free survival was higher in patients receiving PEG-ASNase than those receiving L-ASNase (42.4% and 18.7%). The observed adverse reactions included allergic reactions, pancreatic lesions, gastrointestinal reactions and liver function damage. The incidence of gastrointestinal reactions and liver function damage was higher in the L-ASNase group than that in PEG-ASNase group (45.45% and 33.33%).CONCLUSIONThis study provides valuable insights into the asparaginase treatments in clinical, highlighting the importance of PEG-ASNase for improving treatment protocols in adult ALL patients.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Lymphoblastic Leukemia	Preclinical	US	Expression Therapeutics LLC	11 Dec 2023
Acute Lymphoblastic Leukemia	Preclinical	US	Emory University	11 Dec 2023

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