Efficacy and safety of recombinant E-coli asparaginase in children with previously untreated acute lymphoblastic leukemia: A randomized multicenter study of the Dutch Childhood Oncology Group

Autor: Gertjan J.L. Kaspers, Hans Jürgen Kühnel, Wim J. E. Tissing, Rob Pieters, Cor van den Bos, Marc Bierings, Wouter J.W. Kollen, Thorsten König, Maroeska te Loo, Uwe Pichlmeier, Inge M. van der Sluis, Hester A. de Groot-Kruseman
Přispěvatelé: Paediatric Oncology, CCA - Cancer Treatment and Quality of Life, Pediatric surgery, CCA - Cancer Treatment and quality of life, Pediatrics
Rok vydání: 2018
Předmět:
Male
efficacy
Gastroenterology
Pediatrics
law.invention
pediatric acute lymphoblastic leukemia
chemistry.chemical_compound
0302 clinical medicine
Randomized controlled trial
law
randomized trial
Medicine
Cumulative incidence
Child
Hematology
Immunogenicity
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Perinatology
Recombinant Proteins
and Child Health
Treatment Outcome
Oncology
Child
Preschool
030220 oncology & carcinogenesis
Toxicity
Female
recombinant asparaginase
medicine.drug
medicine.medical_specialty
Asparaginase
Adolescent
Antineoplastic Agents
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
Internal medicine
Escherichia coli
Humans
Pediatrics
Perinatology
and Child Health
Pegaspargase
business.industry
Infant
toxicity
Minimal residual disease
chemistry
Pediatrics
Perinatology and Child Health
business
030215 immunology
Zdroj: Pediatric Blood & Cancer, 65,
Pediatric blood & cancer, 65(8):e27083. Wiley-Liss Inc.
Pediatric Blood & Cancer, 65, 8, pp.
van der Sluis, I M, de Groot-Kruseman, H, te Loo, M, Tissing, W J E, van den Bos, C, Kaspers, G J L, Bierings, M, Kollen, W J W, König, T, Pichlmeier, U, Kühnel, H-J R & Pieters, R 2018, ' Efficacy and safety of recombinant E. coli asparaginase in children with previously untreated acute lymphoblastic leukemia: A randomized multicenter study of the Dutch Childhood Oncology Group ', Pediatric Blood and Cancer, vol. 65, no. 8, e27083 . https://doi.org/10.1002/pbc.27083
Pediatric Blood and Cancer, 65(8):e27083. Wiley-Liss Inc.
Pediatric Blood & Cancer, 65(8):e27083. Wiley-Liss Inc.
Pediatric Blood and Cancer, 65. Wiley-Liss Inc.
ISSN: 1545-5017
1545-5009
DOI: 10.1002/pbc.27083
Popis: Background: The efficacy and safety of recombinant Escherichia coli–asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac). Methods: One hundred and ninety-nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5,000 U/m² during induction (eight doses) and 10,000 U/m² during the postinduction phase (only high-risk patients; standard- and medium-risk patients received pegaspargase). Results: Median trough serum asparaginase activity levels were comparable between both groups; they ranged from 143 to 182 U/l during induction and were above the target value of 100 U/l. Complete asparagine depletion in serum was achieved in 97.9% of patients, with no significant differences between both groups. On day 33 (end of induction), only two (2%) evaluable patients in each group had measurable asparagine serum levels, and complete asparagine depletion in the cerebrospinal fluid was achieved in 98.8% and 93.6% of the patients with rASNase and Asparaginase medac, respectively. During induction, 2.1% and 5% of patients developed an allergic reaction to rASNase or Asparaginase medac, respectively. Approximately 41% of the patients in both groups had a clinical allergy or enzyme inactivation to the first dose of any asparaginase preparation in postinduction. A comparable proportion of patients in both groups developed anti-asparaginase antibodies (57%) during repeated administration of asparaginase. Minimal residual disease levels at the end of induction, 5-year event-free survival, and 5-year cumulative incidence of relapse did not differ between both groups. Conclusion: The efficacy, safety, and immunogenicity of both asparaginase preparations are comparable. This trial was registered at www.clinicaltrials.gov as #NCT00784017; EudraCT number 2006-003180-31.
Databáze: OpenAIRE
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