Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol

作者：Raja Raheel A; Schmiegelow Kjeld; Albertsen Birgitte K; Prunsild Kaie; Zeller Bernward; Vaitkeviciene Goda; Abrahamsson Jonas; Heyman Mats; Taskinen Mervi; Harila Saari Arja; Kanerva Jukka; Frandsen Thomas L^*

来源：British Journal of Haematology, 2014, 165(1): 126-133.

DOI：10.1111/bjh.12733

• leukaemia
• toxicity
• L-asparaginase
• risk factors
• pancreatitis

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 (1-17years) 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) 1000iu/m(2)/dose at 2-6weeks intervals, with a total of 30weeks 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 center dot 9%. AAP occurred after a median of five doses (range 1-13), and 11d (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.

• 出版日期2014-4