Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol
Raheel A. Raja
Department of Paediatric and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorKjeld Schmiegelow
Department of Paediatric and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark
Faculty of Medicine, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorBirgitte K. Albertsen
Department of Paediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark
Search for more papers by this authorKaie Prunsild
Department of Oncohaematology, Tallinn Children's Hospital, Tallinn, Estonia
Search for more papers by this authorBernward Zeller
Department of Paediatrics, Oslo University Hospital, Oslo, Norway
Search for more papers by this authorGoda Vaitkeviciene
Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
Search for more papers by this authorJonas Abrahamsson
Department of Clinical Sciences, Queen Silvia's Children's Hospital, Gothenburg, Sweden
Search for more papers by this authorMats Heyman
Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorMervi Taskinen
Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
Search for more papers by this authorArja Harila-Saari
Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorJukka Kanerva
Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
Search for more papers by this authorCorresponding Author
Thomas L. Frandsen
Department of Paediatric and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark
Correspondence: Thomas L. Frandsen,
Department of Paediatrics, Department 5054,
the University Hospital Rigshospitalet,
Blegdamsvej 9, 2100 Copenhagen, Denmark.
E-mail: [email protected]
Search for more papers by this authorthe Nordic Society of Paediatric Haematology and Oncology (NOPHO) group
Search for more papers by this authorRaheel A. Raja
Department of Paediatric and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorKjeld Schmiegelow
Department of Paediatric and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark
Faculty of Medicine, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorBirgitte K. Albertsen
Department of Paediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark
Search for more papers by this authorKaie Prunsild
Department of Oncohaematology, Tallinn Children's Hospital, Tallinn, Estonia
Search for more papers by this authorBernward Zeller
Department of Paediatrics, Oslo University Hospital, Oslo, Norway
Search for more papers by this authorGoda Vaitkeviciene
Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
Search for more papers by this authorJonas Abrahamsson
Department of Clinical Sciences, Queen Silvia's Children's Hospital, Gothenburg, Sweden
Search for more papers by this authorMats Heyman
Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorMervi Taskinen
Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
Search for more papers by this authorArja Harila-Saari
Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorJukka Kanerva
Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
Search for more papers by this authorCorresponding Author
Thomas L. Frandsen
Department of Paediatric and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark
Correspondence: Thomas L. Frandsen,
Department of Paediatrics, Department 5054,
the University Hospital Rigshospitalet,
Blegdamsvej 9, 2100 Copenhagen, Denmark.
E-mail: [email protected]
Search for more papers by this authorthe Nordic Society of Paediatric Haematology and Oncology (NOPHO) group
Search for more papers by this authorSummary
L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase-intensive protocol has been poorly reported. Children (1–17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L-asparginase (PEG-asparaginase) 1000 iu/m2/dose at 2–6 weeks intervals, with a total of 30 weeks of exposure to PEG-asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1–13), and 11 d (median) from the latest administration of PEG-Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re-exposed to L-asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re-exposure to PEG-asparaginase in ALL patients with mild AAP seems safe.
Supporting Information
| Filename | Description |
|---|---|
| bjh12733-sup-0001-TableS1.docxWord document, 12.5 KB | Table S1. Univariate and multivariate hazard ratios for asparaginase associated pancreatitis. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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