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: Raheel A Raja, Kjeld Schmiegelow, Birgitte K Albertsen, Kaie Prunsild, Bernward Zeller, Goda Vaitkeviciene, Jonas Abrahamsson, Mats Heyman, Mervi Taskinen, Arja Harila-Saari, Jukka Kanerva, Thomas L Frandsen, Nordic Society of Paediatric Haematology and Oncology (NOPHO) group
• Journal: British journal of haematology (Br J Haematol) Vol. 165 Issue 1 Pg. 126-33 (Apr 2014) ISSN: 1365-2141 [Electronic] England
• PMID: 24428625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents
• Polyethylene Glycols
• pegaspargase
• Asparaginase

Topics

• Adolescent
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Asparaginase (adverse effects, therapeutic use)
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Male
• Pancreatitis (chemically induced)
• Polyethylene Glycols (adverse effects, therapeutic use)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (complications, drug therapy)
• Treatment Outcome