Latent onset of clinical pancreatitis in children receiving l-asparaginase therapy

The pancreatic toxicity of L-asparaginase manifested in 43 children (48 trials of therapy) is presented. Seven of the 43 children (16.2%) developed evidence of pancreatitis. Five of the 43 children developed transient hyperglycemia or diabetes mellitus (11.6%). Pancreatitis secondary to L-asparaginase therapy has been reported to occur during administration of the drug. In contrast, 4 of our 7 patients with acute pancreatitis secondary to L-asparaginase developed their disease 4 days to 10 weeks after therapy was stopped. Five of these 7 patients who developed pancreatitis were females greater than 9 years of age. Since estrogens potentiate activity of L-asparaginase in vivo in animal studies, these data raise the question that pubertal females may be at greater risk of acquiring pancreatic toxicity from L-asparaginase than their male counterparts.