Justyna Walenciak1, Krystyna Wyka2, Szymon Janczar1, Wojciech Młynarski1, Beata Zalewska-Szewczyk3. 1. Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Łódź, Poland. 2. Laboratory of Immunopathology and Genetics, Medical University of Lodz, Łódź, Poland. 3. Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Łódź, Poland. Electronic address: beata.zalewska-szewczyk@umed.lodz.pl.
Abstract
BACKGROUND: L-asparaginase (L-asp) remains one of the key components of acute lymphoblastic leukemia therapy. Immune reactions to the drug are associated with its diminished activity. The aim of the study was to determine the level of IgM, IgG and IgE-class anti-L-asp antibodies during the induction and reinduction phases of acute lymphoblastic leukemia therapy and their influence on L-asp activity. METHODS: The study group comprised 65 patients treated for acute lymphoblastic leukemia in one pediatric oncology center. L-asp antibodies were assessed using ELISA at the end of the induction and reinduction phases. L-asp activity was assessed prior to each drug administration by colorimetry. RESULTS: At the end of the first exposure to L-asp antibodies were detected in 35 patients (54%). In the reinduction phase of the treatment anti-L-asp antibodies were found in 38/55 patients (69%). In the induction phase patients with inadequate L-asp activity had higher IgM concentrations (median 5.88 versus 2.81 μg/mL, p = 0.03). In the reinduction phase IgG and IgM levels correlated inversely with L-asp activity. Patients with L-asp allergy had higher levels of IgG (median 61.6 versus 18.36 μg/mL, p = 0.01), whereas higher IgE levels were noted in the group of patients with inadequate drug activity (median 0.91 versus 0.64 μg/mL, p = 0.03). CONCLUSIONS: Subsequent exposure to L-asp in the treatment of acute lymphoblastic leukemia was associated with the increase of anti-L-asp antibodies in all studied classes. However, the changes observed in specific classes of antibodies were not distinctive for L-asp hypersensitivity or inactivation, suggesting that the mechanism is more complex.
BACKGROUND:L-asparaginase (L-asp) remains one of the key components of acute lymphoblastic leukemia therapy. Immune reactions to the drug are associated with its diminished activity. The aim of the study was to determine the level of IgM, IgG and IgE-class anti-L-asp antibodies during the induction and reinduction phases of acute lymphoblastic leukemia therapy and their influence on L-asp activity. METHODS: The study group comprised 65 patients treated for acute lymphoblastic leukemia in one pediatric oncology center. L-asp antibodies were assessed using ELISA at the end of the induction and reinduction phases. L-asp activity was assessed prior to each drug administration by colorimetry. RESULTS: At the end of the first exposure to L-asp antibodies were detected in 35 patients (54%). In the reinduction phase of the treatment anti-L-asp antibodies were found in 38/55 patients (69%). In the induction phase patients with inadequate L-asp activity had higher IgM concentrations (median 5.88 versus 2.81 μg/mL, p = 0.03). In the reinduction phase IgG and IgM levels correlated inversely with L-asp activity. Patients with L-aspallergy had higher levels of IgG (median 61.6 versus 18.36 μg/mL, p = 0.01), whereas higher IgE levels were noted in the group of patients with inadequate drug activity (median 0.91 versus 0.64 μg/mL, p = 0.03). CONCLUSIONS: Subsequent exposure to L-asp in the treatment of acute lymphoblastic leukemia was associated with the increase of anti-L-asp antibodies in all studied classes. However, the changes observed in specific classes of antibodies were not distinctive for L-asphypersensitivity or inactivation, suggesting that the mechanism is more complex.