title: Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol.
abstract: 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/m(2) /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.
authors.affiliation: Department of Paediatric and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Raheel A
authors.initials: RA
authors.lastname: Raja
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
authors.forename: Birgitte K
authors.initials: BK
authors.lastname: Albertsen
authors.forename: Kaie
authors.initials: K
authors.lastname: Prunsild
authors.forename: Bernward
authors.initials: B
authors.lastname: Zeller
authors.forename: Goda
authors.initials: G
authors.lastname: Vaitkeviciene
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
authors.forename: Mervi
authors.initials: M
authors.lastname: Taskinen
authors.forename: Arja
authors.initials: A
authors.lastname: Harila-Saari
authors.forename: Jukka
authors.initials: J
authors.lastname: Kanerva
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Frandsen
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced*; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase
keywords: L-asparaginase; leukaemia; pancreatitis; risk factors; toxicity