Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma in Belgium

Veerle Mondelaers, Alina Ferster, Anne Uyttebroeck, Bénédicte Brichard, Jutte van der Werff Ten Bosch, Koenraad Norga, Nadine Francotte, Caroline Piette, Katrien Vandemeulebroecke, Charlotte Verbeke, Susanne Schmidt, Yves Benoit, Tim Lammens, Barbara De Moerloose

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Asparaginase (ASNase) is an important anti-leukaemic drug in the treatment of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL). A substantial proportion of patients develop hypersensitivity reactions with anti-ASNase neutralising antibodies, resulting in allergic reactions or silent inactivation (SI), and characterised by inactivation and rapid clearance of ASNase. We report results of a prospective, real-time therapeutic drug monitoring of pegylated Escherichia coli (PEG-)ASNase and Erwinia ASNase in children treated for ALL and NHL in Belgium. Erwinia ASNase was given as second-line after hypersensitivity to PEG-ASNase. In total, 286 children were enrolled in the PEG-ASNase cohort. Allergy was seen in 11·2% and SI in 5·2% of patients. Of the 42 patients treated with Erwinia ASNase, 7·1% experienced allergy and 2·4% SI. The median trough PEG-ASNase activity was high in all patients without hypersensitivity. After Erwinia administration significantly more day 3 samples had activities <100 IU/l (62·5% vs. 10% at day 2 (D2)). The median D2 activity was significantly higher for intramuscular (IM; 347 IU/l) than for intravenous Erwinia administrations (159 IU/l). This prospective, multicentre study shows that monitoring of ASNase activity during treatment of children with ALL and NHL is feasible and informative. Treatment with Erwinia ASNase warrants close monitoring and optimally adherence to a 2-day interval of IM administrations.

Original languageEnglish
Pages (from-to)105-114
Number of pages10
JournalBritish Journal of Haematology
Volume190
Issue number1
DOIs
Publication statusPublished - Jul 2020

Bibliographical note

© 2020 British Society for Haematology and John Wiley & Sons Ltd.

Keywords

  • acute lymphoblastic leukaemia
  • allergy
  • asparaginase
  • childhood
  • silent inactivation
  • therapeutic drug monitoring

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