Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma in Belgium
Corresponding Author
Veerle Mondelaers
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital and Cancer Research Institute Ghent, Ghent, Belgium
Correspondence: Veerle Mondelaers, Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, 10 Corneel Heymanslaan (Administratieve Pediatrie), B-9000 Ghent, Belgium.
E-mail: [email protected]
Search for more papers by this authorAlina Ferster
Pediatric Hematology-Oncology, Hôpital Universitaire des Enfants Reine Fabiola (HUDERF-UKZKF), Brussels, Belgium
Search for more papers by this authorAnne Uyttebroeck
Pediatric Hematology-Oncology, University Hospital Gasthuisberg, Leuven, Belgium
Search for more papers by this authorBénédicte Brichard
Pediatric Hematology-Oncology, Cliniques Universitaires Saint-Luc (UCL), Brussels, Belgium
Search for more papers by this authorJutte van der Werff ten Bosch
Pediatric Hematology-Oncology, UZ Brussel, Brussels, Belgium
Search for more papers by this authorKoenraad Norga
Pediatric Hematology-Oncology, University Hospital Antwerp, Antwerp, Belgium
Search for more papers by this authorNadine Francotte
Department of Pediatric Oncology, CHC- Hospital of Hope, Montegnée, Belgium
Search for more papers by this authorCaroline Piette
Department of Pediatric Oncology, CHR Citadelle, Liège, Belgium
Search for more papers by this authorKatrien Vandemeulebroecke
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorCharlotte Verbeke
Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
Search for more papers by this authorSusanne Schmidt
Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
Search for more papers by this authorYves Benoit
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital and Cancer Research Institute Ghent, Ghent, Belgium
Search for more papers by this authorTim Lammens
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital and Cancer Research Institute Ghent, Ghent, Belgium
These authors contributed equally to this study.Search for more papers by this authorBarbara De Moerloose
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital and Cancer Research Institute Ghent, Ghent, Belgium
These authors contributed equally to this study.Search for more papers by this authorCorresponding Author
Veerle Mondelaers
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital and Cancer Research Institute Ghent, Ghent, Belgium
Correspondence: Veerle Mondelaers, Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, 10 Corneel Heymanslaan (Administratieve Pediatrie), B-9000 Ghent, Belgium.
E-mail: [email protected]
Search for more papers by this authorAlina Ferster
Pediatric Hematology-Oncology, Hôpital Universitaire des Enfants Reine Fabiola (HUDERF-UKZKF), Brussels, Belgium
Search for more papers by this authorAnne Uyttebroeck
Pediatric Hematology-Oncology, University Hospital Gasthuisberg, Leuven, Belgium
Search for more papers by this authorBénédicte Brichard
Pediatric Hematology-Oncology, Cliniques Universitaires Saint-Luc (UCL), Brussels, Belgium
Search for more papers by this authorJutte van der Werff ten Bosch
Pediatric Hematology-Oncology, UZ Brussel, Brussels, Belgium
Search for more papers by this authorKoenraad Norga
Pediatric Hematology-Oncology, University Hospital Antwerp, Antwerp, Belgium
Search for more papers by this authorNadine Francotte
Department of Pediatric Oncology, CHC- Hospital of Hope, Montegnée, Belgium
Search for more papers by this authorCaroline Piette
Department of Pediatric Oncology, CHR Citadelle, Liège, Belgium
Search for more papers by this authorKatrien Vandemeulebroecke
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorCharlotte Verbeke
Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
Search for more papers by this authorSusanne Schmidt
Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
Search for more papers by this authorYves Benoit
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital and Cancer Research Institute Ghent, Ghent, Belgium
Search for more papers by this authorTim Lammens
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital and Cancer Research Institute Ghent, Ghent, Belgium
These authors contributed equally to this study.Search for more papers by this authorBarbara De Moerloose
Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital and Cancer Research Institute Ghent, Ghent, Belgium
These authors contributed equally to this study.Search for more papers by this authorSummary
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.
Conflict of interest
Veerle Mondelaershas participated in advisory boards for Jazz Pharmaceuticals and received travel expenses and speaker's fees from Jazz Pharmaceuticals and Shire. Tim Lammens and Barbara De Moerloose received travel expenses from Jazz Pharmaceuticals. The authors declare no competing financial interests.
Supporting Information
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Data S1. Supplementary methods. |
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