Predictive factors for L-asparaginase hypersensitivity in pediatric acute lymphoblastic leukemia

Int J Hematol. 2024 Apr;119(4):442-449. doi: 10.1007/s12185-024-03725-z. Epub 2024 Feb 29.

Abstract

Background: L-Asparaginase is a crucial component of acute lymphoblastic leukemia (ALL) treatment. However, hypersensitivity is a common adverse event. This study aimed to identify risk factors for L-asparaginase hypersensitivity in childhood ALL.

Methods: Children treated for ALL at Chiang Mai University Hospital, Thailand, between 2005 and 2020 were included. Demographic data, clinical characteristics, and factors related to L-asparaginase were retrospectively reviewed.

Results: L-Asparaginase hypersensitivity was observed in 24 of 216 children with ALL (11.1%). All patients received native L-asparaginase intramuscularly, and events occurred exclusively during the post-induction phase without concurrent corticosteroid use. Univariable analysis showed that relapsed ALL, higher accumulated doses, increased exposure days, and longer interval between drug administrations were potential risk factors. In multivariable logistic regression analysis, interruption of L-asparaginase administration for ≥ 52 weeks and exposure duration of ≥ 15 days were independent risk factors, with adjusted odds ratio of 16.481 (95% CI 3.248-83.617, p = 0.001) and 4.919 (95% CI 1.138-21.263, p = 0.033), respectively.

Conclusions: Children with ALL who require re-exposure to L-asparaginase after 52-week interruption or who have received L-asparaginase for ≥ 15 exposure days are at risk of developing L-asparaginase hypersensitivity. Further management strategies in this setting should be evaluated.

Keywords: l-Asparaginase; Acute lymphoblastic leukemia; Hypersensitivity; Pediatric.

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asparaginase / adverse effects
  • Child
  • Drug Hypersensitivity* / drug therapy
  • Drug Hypersensitivity* / epidemiology
  • Drug Hypersensitivity* / etiology
  • Humans
  • Polyethylene Glycols
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / complications
  • Retrospective Studies
  • Risk Factors

Substances

  • Asparaginase
  • Antineoplastic Agents
  • Polyethylene Glycols