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Predictive factors for L-asparaginase hypersensitivity in pediatric acute lymphoblastic leukemia
Chane Choed-Amphai1, Jiraporn Khorana2,3,4, Lalita Sathitsamitphong5
1Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, 110 Intawaroros Road, Sriphum, Muang, Chiang Mai, 50200, Thailand. chane.c@cmu.ac.th.
Insights
Children with acute lymphoblastic leukemia (ALL) receiving L-asparaginase may develop hypersensitivity. Risk factors include re-exposure after a 52-week break or prolonged treatment duration of 15 days.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Pharmacology
Background:
- L-asparaginase is essential for treating acute lymphoblastic leukemia (ALL).
- Hypersensitivity reactions to L-asparaginase are a significant clinical challenge.
- Identifying risk factors for hypersensitivity is crucial for optimizing ALL treatment.
Purpose of the Study:
- To determine risk factors associated with L-asparaginase hypersensitivity in children with ALL.
- To analyze demographic and clinical data to predict hypersensitivity events.
- To inform treatment strategies and improve patient outcomes in pediatric ALL.
Main Methods:
- Retrospective review of children diagnosed with ALL at Chiang Mai University Hospital (2005-2020).
- Analysis of demographic, clinical, and L-asparaginase-related factors.
- Multivariable logistic regression to identify independent risk factors for hypersensitivity.
Main Results:
- L-asparaginase hypersensitivity occurred in 11.1% of 216 children with ALL.
- Independent risk factors identified: L-asparaginase interruption for ≥52 weeks (aOR 16.481) and exposure duration of ≥15 days (aOR 4.919).
- Hypersensitivity events were noted during the post-induction phase without concurrent corticosteroids.
Conclusions:
- Children with ALL requiring L-asparaginase re-exposure after a 52-week interruption are at high risk.
- Prolonged L-asparaginase exposure (≥15 days) increases the risk of hypersensitivity.
- Further research into management strategies for at-risk patients is warranted.
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.
