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. Pediatr Blood Cancer 2007;49:634-639. 0 2006 Wiley-Liss, Inc.