Breakthrough reactions in pediatric chemotherapeutic desensitization: Outcomes and associated risk factors

Rapid drug desensitization (RDD) enables the safe reintroduction of chemotherapeutic agents in patients with hypersensitivity reactions (HSRs). However, some patients experience breakthrough reactions (BTRs) during desensitization, and research on factors associated with BTRs is limited in pediatric patients.

We conducted an ambispective observational cross-sectional study in Bangkok, Thailand. Patients ≤18-year-old who experienced immediate HSRs (within 1-6 h) to chemotherapeutic agents and underwent RDD following evaluation by allergists between January 2010 and April 2025 were included.

A total of 182 RDDs were performed in 38 children (median age of 5.3 years). The majority were diagnosed with acute leukemia (47.4%), and the most common causative agents for HSRs were E. coli-Asparaginase (26.9%), vincristine (24.7%), and methotrexate (13.7%). Asparaginase, vincristine, cyclophosphamide, carboplatin/oxaliplatin, and doxorubicin were commonly associated with Type I HSRs, while methotrexate, cyclosporin A and etoposide were linked to Type I HSRs as well as infusion-related reactions (IRRs) or cytokine-release reactions (CRRs). Twenty-nine BTRs occurred during RDD (15.9%), most of which were mild (72.4%). Independent risk factors for BTRs included E. coli-Asparaginase desensitization (adjusted OR 3.87 [1.45, 10.39], p = .007), and a higher initial starting dose (ratio ≤1:10,000) (adjusted OR 3.51 [1.02, 12.18], p = .048). Conversely, later cycles of desensitization reduced the risk of BTRs (adjusted OR 0.47 [0.31, 0.72], p < .001).

RDDs for chemotherapeutic agents effectively enable safe treatment continuation in most children with immediate HSRs, including type I HSR, CRR, and mixed reactions. In our study, E. coli-Asparaginase, a higher initial starting dose, and an early desensitization cycle were identified as having potential risk factors associated with BTRs.