Asparaginase (ASP) is an essential component for the acute lymphoblastic leukemia (ALL) treatment, but toxicities, such as allergy, frequently limit its use. Although the potentially lower PEG-ASP formulation immunogenicity, few studies with conflicting results have compared the allergy incidence between Escherichia coli-ASP and PEG-ASP in the same protocol. We aimed at comparing the allergy incidence in children receiving native E. coli-ASP versus PEG-ASP within the same clinical protocol (Spanish Society of Pediatric Hematology and Oncology ALL-SEHOP-PETHEMA 2013). One hundred and twenty-six children (1-19 years) diagnosed with ALL from 2013 to 2020 were included. Patients in group 1 received a sequential scheme of native E. coli-ASP 10,000 IU/m2 intramuscularly (IM) followed by PEG-ASP 1000 IU/m2 IM. Patients in group 2 received PEG-ASP 1000 IU/m2 IM upfront. Clinical allergy incidence was compared between both groups. Serum ASP activity (SAA) was measured in a subgroup of patients, and silent inactivation was recorded. The cumulative incidence of clinical allergy was significantly higher in group 1 (native followed by PEG-ASP) than in group 2 (PEG-ASP upfront), 24.7% versus 4.1% (p = 0.0085). Adequate ASP activity was achieved with PEG-ASP 1000 IU/m2 dose in most patients (median SAA 412.5 and 453.0 IU/L at days 7 and 14). The incidence of silent inactivation in PEG-ASP upfront patients was very low. PEG-ASP-used upfront was associated with a lower incidence of clinical allergy than that observed in the sequential use of native E. coli-ASP followed by PEG-ASP. PEG-ASP at 1000 IU/m2 was effective in achieving enough ASP activity in most patients.
Keywords: acute lymphoblastic leukemia; allergy; asparaginase; pediatrics; therapeutic drug monitoring; toxicity.
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