Successful management of severe L-asparaginase-associated pancreatitis by continuous regional arterial infusion of protease inhibitor and antibiotic

BACKGROUND. L-asparaginase is a key drug in the treatment of childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). However, L-asparaginase can cause a fatal complication of pancreatitis, and an effective treatment for L-asparaginase-associated pancreatitis (AAP) has not been developed to date. The authors investigated whether rapidly treating children with AAP by continuous regional arterial infusion (CRAI) of protease inhibitor and antibiotic would quickly resolve AAP. METHODS. Between 2000 and 2007, 104 pediatric patients with ALL or LBL were treated at the authors' affiliated hospitals with intensive regimens that included Escherichia coli-derived L-asparaginase. Six of 104 patients developed severe AAP One patient was treated with intravenous infusion of protease inhibitor, and (he remaining 5 patients received CRAI of protease inhibitor and antibiotic within 48 hours of the onset of AAP. RESULTS. The patient who received intravenous protease inhibitor had pseudocyst formation and developed a subsequent leukemic recurrence after the interruption of chemotherapy for 4.5 months. In the other patients, AAP subsided within 2 to 6 days after the start of CRAI, and serious complications did not emerge. Significantly, chemotherapy could be resumed within 4 weeks (range, 12-23 days) after the onset of AAP and the patients were in complete remission from 4 months to 44 months with further chemotherapy that excluded L-asparaginase. CONCLUSIONS. The current results indicated that early introduction of CRAI of protease inhibitor and antibiotic is suitable for treating severe AAP.