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Lookup NU author(s): Professor Anthony MoormanORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. In successive UK clinical trials (UKALL 2003, UKALL 2011) for paediatric acute lymphoblastic leukaemia (ALL), polyethylene glycol-conjugated E. coli L-asparaginase (PEG-EcASNase) 1000 iu/m2 was administered intramuscularly with risk-stratified treatment. In induction, patients received two PEG-EcASNase doses, 14 days apart. Post-induction, non-high-risk patients (Regimens A, B) received 1–2 doses in delayed intensification (DI) while high-risk Regimen C patients received 6–10 PEG-EcASNase doses, including two in DI. Trial substudies monitored asparaginase (ASNase) activity, ASNase-related toxicity and ASNase-associated antibodies (total, 1112 patients). Median (interquartile range) trough plasma ASNase activity (14 ± 2 days post dose) following first and second induction doses and first DI dose was respectively 217 iu/l (144–307 iu/l), 265 iu/l (165–401 iu/l) and 292 iu/l (194–386 iu/l); 15% (138/910) samples showed subthreshold ASNase activity (<100 iu/l) at any trough time point. Older age was associated with lower (regression coefficient −9.5; p < 0.0001) and DI time point with higher ASNase activity (regression coefficient 29.9; p < 0.0001). Clinical hypersensitivity was observed in 3.8% (UKALL 2003) and 6% (UKALL 2011) of patients, and in 90% or more in Regimen C. A 7% (10/149) silent inactivation rate was observed in UKALL 2003. PEG-EcASNase schedule in UKALL paediatric trials is associated with low toxicity but wide interpatient variability. Therapeutic drug monitoring potentially permits optimisation through individualised asparaginase dosing.
Author(s): Sidhu J, Masurekar AN, Gogoi MP, Fong C, Ioannou T, Lodhi T, Parker C, Liu J, Kirkwood AA, Moorman AV, Das K, Goulden NJ, Vora A, Saha V, Krishnan S
Publication type: Article
Publication status: Published
Journal: British Journal of Haematology
Year: 2022
Volume: 198
Issue: 1
Pages: 142-150
Print publication date: 01/07/2022
Online publication date: 29/03/2022
Acceptance date: 11/03/2022
Date deposited: 26/04/2022
ISSN (print): 0007-1048
ISSN (electronic): 1365-2141
Publisher: Wiley-Blackwell Publishing Ltd.
URL: https://doi.org/10.1111/bjh.18158
DOI: 10.1111/bjh.18158
PubMed id: 35348200
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