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Asparaginase, a critical component of current pediatric acute leukemia treatment protocols, is associated with a number of serious side effects, one of which is pancreatitis. Pancreatitis can result in significant morbidity and mortality from necrosis, pseudocyst formation, hemorrhage, systemic inflammation, intestinal perforation, and sepsis. Another rare complication of pancreatitis is posterior reversible encephalopathy syndrome, likely mediated by systemic inflammation secondary to pancreatic autodigestion and proinflammatory cytokine-mediated vascular endothelial damage. Here, we review this association in the literature and report 2 pediatric patients with leukemia who developed posterior reversible encephalopathy syndrome in the setting of asparaginase-associated pancreatitis.

Imatinib, a tyrosine kinase inhibitor has improved survival in pediatric patients with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. There are no formal drug interactions listed between methotrexate and tyrosine kinase inhibitors. Four pediatric patients with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia had delayed methotrexate clearance during their first cycle of high-dose methotrexate while receiving imatinib, resulting in acute kidney injury. For subsequent high-dose methotrexate cycles, imatinib was withheld resulting in decreased acute kidney injury, shorter time to methotrexate clearance, less toxicity, and shorter hospitalizations. For pediatric patients with acute lymphoblastic leukemia receiving imatinib, we recommend escalated supportive care measures including increased hyperhydration and leucovoruin frequency. For patients with toxicities secondary to delayed clearance or need for glucarpidase, we recommend holding imatinib with subsequent high-dose methotrexate courses.