Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation
| Autor: | Sofie Gottschalk Højfeldt, Thomas Frandsen, Henrik Daa Schrøder, Birgitte Klug Albertsen, Peder Skov Wehner, Kjeld Schmiegelow, Louise Tram Henriksen |
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| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty Asparaginase Adolescent medicine.medical_treatment Antineoplastic Agents Gastroenterology Immunoglobulin G Antibodies Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Internal medicine PEG ratio Journal Article Medicine Humans Child Childhood Acute Lymphoblastic Leukemia Chemotherapy biology business.industry Infant Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Surgery Leukemia Oncology chemistry 030220 oncology & carcinogenesis Child Preschool Pediatrics Perinatology and Child Health biology.protein Female Antibody business 030215 immunology |
| Zdroj: | Tram Henriksen, L, Gottschalk Højfeldt, S, Schmiegelow, K, Frandsen, T L, Skov Wehner, P, Schrøder, H, Klug Albertsen, B & Nordic Society of Pediatric Hematology and Oncology, NOPHO Group 2017, ' Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation ', Pediatric Blood & Cancer, vol. 64, no. 12 . https://doi.org/10.1002/pbc.26686 Tram Henriksen, L, Gottschalk Højfeldt, S, Schmiegelow, K, Frandsen, T L, Skov Wehner, P, Schrøder, H, Klug Albertsen, B & Nordic Society of Pediatric Hematology and Oncology, NOPHO Group 2017, ' Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol : Pharmacokinetics and antibody formation ', Pediatric Blood & Cancer, vol. 64, no. 12, e26686 . https://doi.org/10.1002/pbc.26686 |
| ISSN: | 1545-5017 |
| DOI: | 10.1002/pbc.26686 |
| Popis: | BACKGROUND: As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment.METHODS: The aim of this study was to evaluate the pharmacokinetics of prolonged upfront biweekly PEG-asparaginase (where PEG is polyethylene glycol) treatment by measuring serum l-asparaginase activity and formation of anti-PEG-asparaginase antibodies. A total of 97 evaluable patients (1-17 years), diagnosed with ALL, and treated according to the NOPHO ALL2008 protocol (where NOPHO is Nordic Society of Paediatric Haematology and Oncology) were included. In the NOPHO ALL2008 protocol, patients are randomized to 8 or 15 doses of intramuscular PEG-asparaginase (Oncaspar(®) ) 1,000 IU/m²/dose, at 2-week or 6-week intervals with a total of 30-week treatment (Clinical trials.gov. no.: NCT00819351).RESULTS: The pharmacological target of treatment (l-asparaginase activity above 100 IU/l) was reached in 612 of 652 (94%) samples obtained 14 ± 2 days after PEG-asparaginase administration. Mean l-asparaginase activity was 338 IU/l. Six patients had l-asparaginase activity below 50 IU/l in all samples. A total of 25 patients (26%) developed Immunoglobulin G (IgG) anti-PEG-asparaginase antibodies, but there was no correlation between anti-PEG-asparaginase antibodies and low levels of asparaginase activity.CONCLUSION: We conclude that prolonged first-line biweekly PEG-asparaginase therapy, 1,000 IU/m²/dose was above the pharmacological target in the vast majority of patients. Presence of anti-PEG-asparaginase antibodies was not a predictor of l-asparaginase activity. |
| Databáze: | OpenAIRE |
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