Hydrolyzes asparagine to aspartate and ammonia.
An enzyme that causes depletion of the extra cellular asparagine by hydrolyzing it into aspartic acid and ammonia.
Lymphoblasts usually have low asparagine synthetase activity and rely on exogenous asparagine for protein synthesis.
Asparagine deficiency can lead to death of lymphoblasts.
Acute lymphoblastic leukemia cells lack asparagine synthetase and are dependent on exogenous sources of asparagine for survival.
With rapid depletion of asparagine ALL cells are selectively killed, whereas normal cells can synthesize asparagine and survive.
Used more commonly in childhood ALL than in adult disease and may contribute to the improved survival of adolescents and young adults.
Three types available: from Escherichia coli, from native E. coli-derived asparaginaase, a pegylated form of asparaginase, and Erwinia chrysanthemia derived asparaginase.
PEG-ASP has decreased immunogenicity and longer half life than the other two drugs and can maintain depletion of asparaginase at an equivalent level to higher doses and prolonged administration of the other agents.
Erwinia asparaginase is improved with therapy of patients with newly diagnosed ALL, or in patients with hypersensitivity to other asparaginase agents.
The half life of E. coli asparaginase, Erwinia asparaginase, Erwinia asparaginase and PEG-asparaginase, are 1.24 days, 0.6 other day, and 5.73 days, respectively.
Erwinia is administered IV or IM 20,000 international units per meter squared 3 times a week, Escherichia coli asparaginase is administered at 6-10,000 international units per meter squared 3 times a week, and pegylated- asparaginase is administered at a dose of 2500 international units per meter squared every 2 weeks.
Treatment is associated with hypersensitivity reactions, pancreatitis, hyperglycemia, coagulation disorders, and hepatic toxicity.
Exposure to bacterial proteins can cause immunologic reactions ranging from localized, transient erythematic and rash to the site of injection to urinary, respiratory distress, and anaphylaxis.
Adverse reactions to coagulation is related to the impairment of protein synthesis, with reductions in plasminogen, fibrinogen, ant thrombin, space and factors IX and X with prolongation of the PTT.
May be associated with protein C and S deficiencies.
May increase risk for bleeding or thrombosis.
Hypofibrinogenemia present in 15 to 65% of treated patients.
Asparaginase therapy in pediatric regimens carries a higher risk of hepatic, pancreatic, and thrombotic complications, and the risk is increased in older or obese patients.
Approximately 40% of patients develop anti-asparaginase antibodies.
The development of antibodies manifests as an allergic reaction.
Between 20-30% of patients develop an allergic reaction to Escherichia coli asparaginaase, will still develop an allergic reaction to Erwinia asparaginase.