Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation

Efficacy and safety of recombinant E. coli asparaginase in children with previously untreated acute lymphoblastic leukemia: A randomized multicenter study of the Dutch Childhood Oncology Group

“…ASNase can induce both neutralizing and non‐neutralizing antibodies, and antibodies of different immunoglobulin classes (IgG, IgM). These antibodies may induce allergic reactions, inactivate the enzyme, or accelerate its elimination . Only 19 of 199 patients were positive for AAAs during induction treatment.…”

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

“…Asparaginase can induce antibody formation that neutralizes asparaginase with or without (so-called silent inactivation) clinical signs of hypersensitivity 154– 156 . Identification of silent inactivation requires measurement of plasma asparaginase activity levels.…”

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

“…[27] Body system Common clinical manifestation Hypersensitivity reaction Infusion reaction Cardiovascular Chest pain, palpitations, hypotension, tachycardia, bradycardia, arrhythmia, edema, ischemia or infarction, cardiac arrest thus been recommended in patients receiving premedication to identify patients who might develop subclinical hypersensitivity. [37] The intensity of treatment and a patient's treatment history also impact the risk of developing hypersensitivity to asparaginase. Reactions are less prevalent in patients treated with high-intensity chemotherapy with little or no breaks in asparaginase treatment.…”

“…[99] An activity threshold of 0.05 IU/mL for asparaginase is lower than the commonly accepted 0.1 IU/mL, and debate exists over what the appropriate cutoff point should be. [37,100] One recent study measuring asparaginase activity levels and plasma asparagine concentrations found that asparagine was completely depleted at higher asparaginase activity levels, but began to rebound once plasma asparaginase activity declined to <0.4 IU/mL. [21] Another modeling study in adult ALL patients found that PEG-asparaginase activity levels of 0.2 IU/mL were required to achieve 90% asparagine depletion.…”