PEG asparaginase (PEG-ASNase) is an essential drug in the treatment of acute lymphoblastic leukemia (ALL). However, asparaginase-related hypersensitivity and silent inactivation continue to represent clinical challenges.

Describe the incidence of hypersensitivity reactions and inactivations associated with PEG-ASNase in Brazilian children undergoing first-line treatment for ALL.

Prospective, multicenter and randomized trial. Patients younger than 18 years with ALL who received PEG-ASNase between February 2021 and February 2024 in eigth differents hospitals were included. ASNase activity was monitored in all patients 7 days and 14 days after each PEG-ASNase.

305 patients were included. 33 (10.8%) patients had clinical allergic reactions and 43 (14.1%) patients had inactivation (asparaginase activity < 0.1 IU/mL). Among those who had allergic reactions, 45.5% also inactivated the drug. There was a significant association between clinical allergic reaction and inactivation (p < 0.001). However, among those who inactivated, 65% did not have an allergic reaction. The silent inactivation rate was 9.2% (n = 28).

Our findings are consistent with the literature, underscoring the importance of therapeutic monitoring of asparaginase for all patients. We aim to further contribute to the treatment of children with ALL by investigating the influence of pre-medication on inactivation and hypersensitivity reactions.