Serum amylase and lipase levels were unchanged during the present study, though serum trypsin levels increased after the ASNase injection. Serum PSTI levels increased after the ASNase injection as well. Acute pancreatitis develops with unregulated trypsin activity after breakdown

of critical protective mechanisms and copious secretion of pancreatic enzymes such as amylase and lipase.[21,22] The present results indicate that inhibitors of trypsin could potentially prevent development of pancreatitis, and suggest the presence of subclinical pancreatitis in cases who do not develop pancreatitis during administration of ASNase. Not only ASNase but also prednisolone has been implicated as an agent capable of inducing pancreatitis.[23] Previous reports suggest that ASNase is the more likely source of pancreatitis on the basis of histologic examination of the pancreas, the relative infrequency of prednisolone-induced check details pancreatitis, and a negative result after rechallenge with prednisolone.[14,18,24] In the present study, one of 29 patients (3%) developed ASNase-induced pancreatitis, similar to the morbidity rates in previous reports.[4,6,9,16,25] Since the patient developed severe pancreatitis, ASNase was contraindicated during the rest of her treatment for ALL. The results of her blood tests were similar to the results from those patients

who did not develop EGFR inhibitor acute pancreatitis, so there was no parameter that could be used to predict acute pancreatitis. When ASNase-induced pancreatitis

occurs, treatment with Erwinia chrysanthemi asparaginase is an option. As it can also lead to pancreatitis, Erwinia asparaginase is a second-line therapy for ALL after hypersensitivity to Escherichia coli asparaginase.[26] Furthermore, there are no widely accepted guidelines for use of Erwinia asparaginase, and such treatment is not covered by health insurance providers in Japan. Previous reports have shown that there is a mean of almost 10 days from the last administration of ASNase to diagnosis of pancreatitis.[5,9,16] Similarly, Japanese case reports of ASNase-induced pancreatitis have shown that 50 of 56 patients (89%) who developed Selleckchem Gemcitabine ASNase-induced pancreatitis did so within 10 days (median 2 days, range 0–23 days) after administration of ASNase.[27] This period is similar to the time period in the present study when the levels of plasma amino acids, serum trypsin, and serum PSTI changed. In the rat model, it has been proposed that ASNase-induced pancreatic injury can involve disruption of the plasma amino acid balance that is caused by ASNase. Disruption of protein synthesis in acinar cells then causes inhibition of exocytosis following the histologic morphologic changes.[28] The present results imply that the plasma amino acid level imbalance could also be a factor in ASNase-induced pancreatitis in humans.