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

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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 center dot 2% of patients. Of the 42 patients treated with Erwinia ASNase, 7 center dot 1% experienced allergy and 2 center dot 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 center dot 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.
Keywords
PEG-ASPARAGINASE, CHILDREN, TRIAL, HYPERSENSITIVITY, RECOMMENDATIONS, DEXAMETHASONE, ADOLESCENTS, CONSENSUS, PROTOCOL, ALLERGY, acute lymphoblastic leukaemia, childhood, asparaginase, allergy, silent, inactivation, therapeutic drug monitoring

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MLA
Mondelaers, Veerle, et al. “Prospective, Real-Time Monitoring of Pegylated Escherichia Coli and Erwinia Asparaginase Therapy in Childhood Acute Lymphoblastic Leukaemia and Non-Hodgkin Lymphoma in Belgium.” BRITISH JOURNAL OF HAEMATOLOGY, 2020.
APA
Mondelaers, V., Ferster, A., Uyttebroeck, A., Brichard, B., ten Bosch, J. der W., Norga, K., … De Moerloose, B. (2020). Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma in Belgium. BRITISH JOURNAL OF HAEMATOLOGY.
Chicago author-date
Mondelaers, Veerle, Alina Ferster, Anne Uyttebroeck, Benedicte Brichard, Juttevan der Werff ten Bosch, Koenraad Norga, Nadine Francotte, et al. 2020. “Prospective, Real-Time Monitoring of Pegylated Escherichia Coli and Erwinia Asparaginase Therapy in Childhood Acute Lymphoblastic Leukaemia and Non-Hodgkin Lymphoma in Belgium.” BRITISH JOURNAL OF HAEMATOLOGY.
Chicago author-date (all authors)
Mondelaers, Veerle, Alina Ferster, Anne Uyttebroeck, Benedicte Brichard, Juttevan der Werff ten Bosch, Koenraad Norga, Nadine Francotte, Caroline Piette, Katrien Vandemeulebroecke, Charlotte Verbeke, Susanne Schmidt, Yves Benoit, Tim Lammens, and Barbara De Moerloose. 2020. “Prospective, Real-Time Monitoring of Pegylated Escherichia Coli and Erwinia Asparaginase Therapy in Childhood Acute Lymphoblastic Leukaemia and Non-Hodgkin Lymphoma in Belgium.” BRITISH JOURNAL OF HAEMATOLOGY.
Vancouver
1.
Mondelaers V, Ferster A, Uyttebroeck A, Brichard B, ten Bosch J der W, Norga K, et al. Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma in Belgium. BRITISH JOURNAL OF HAEMATOLOGY. 2020;
IEEE
[1]
V. Mondelaers et al., “Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma in Belgium,” BRITISH JOURNAL OF HAEMATOLOGY, 2020.
@article{8651282,
  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 center dot 2% of patients. Of the 42 patients treated with Erwinia ASNase, 7 center dot 1% experienced allergy and 2 center dot 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 center dot 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.},
  author       = {Mondelaers, Veerle and Ferster, Alina and Uyttebroeck, Anne and Brichard, Benedicte and ten Bosch, Juttevan der Werff and Norga, Koenraad and Francotte, Nadine and Piette, Caroline and Vandemeulebroecke, Katrien and Verbeke, Charlotte and Schmidt, Susanne and Benoit, Yves and Lammens, Tim and De Moerloose, Barbara},
  issn         = {0007-1048},
  journal      = {BRITISH JOURNAL OF HAEMATOLOGY},
  keywords     = {PEG-ASPARAGINASE,CHILDREN,TRIAL,HYPERSENSITIVITY,RECOMMENDATIONS,DEXAMETHASONE,ADOLESCENTS,CONSENSUS,PROTOCOL,ALLERGY,acute lymphoblastic leukaemia,childhood,asparaginase,allergy,silent,inactivation,therapeutic drug monitoring},
  language     = {eng},
  pages        = {10},
  title        = {Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma in Belgium},
  url          = {http://dx.doi.org/10.1111/bjh.16495},
  year         = {2020},
}

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