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.
Knoderer
Holly M
HM
Department of Pediatric Hematology-Oncology, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA. htalley@iupui.edu
Robarge
Jason
J
Flockhart
David A
DA
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001215:Asparaginase / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D003907:Dexamethasone; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin