Predicting asparaginase-associated pancreatitis.

Background: Pancreatitis is a well-known, but little-understood complication of asparaginase. There is no predictor of who will develop asparaginase-associated pancreatitis (AAP). To better define this population, we present a retrospective analysis regarding AAP and provide a review of the relevant literature.

Methods: We systematically reviewed medical records of 254 asparaginase recipients during a 5-year period. Pancreatitis was defined and graded according to CTCAE v3.0.

Results: Pancreatitis was diagnosed in 48 (19%) patients. Thirty-three (13%) patients were identified as having AAP. Twelve cases occurred after Escherichia coli asparaginase and 20 followed PEG-asparaginase. Pancreatitis was independent of the individual or cumulative asparaginase dose. The interval to pancreatitis diagnosis was longer for PEG-asparaginase than E. coli asparaginase (P = 0.02). AAP was seen more frequently in patients receiving prednisone (P = 0.02) and daunomycin (P = 0.006) while less frequent with dexamethasone (P = 0.04). Other chemotherapy agents appeared to have no association with AAP. As observed by others, those with pancreatitis were older (P = 0.001), but the significance of this remains uncertain.

Conclusions: This study emphasizes our inability to predict who will develop pancreatic toxicity from asparaginase and suggests that those at risk might have an unidentified genetic predisposition.