The Efficacy of Single Dose Rasburicase in Prevention or Treatment of Tumor Lysis Syndrome in Children

Background: Tumor lysis syndrome (TLS) is a major metabolic complication in patients with malignancy after initiation of chemotherapy or spontaneously without treatment. The role of Rasburicase (a recombinant urate-oxidase enzyme) in prevention and treatment of TLS has been demonstrated in recent years. We aimed to investigate the efficacy of a single dose of rasburicase in reducing the risk of TLS in children at high risk.  Methods: we conducted a retrospective analysis of 560 children with various malignancies in a single referral center. On the basis of the reference values previously established in our center hyperuricemia and TLS were defined. Tumor lysis syndrome development was the primary outcome. 48 children with a mean age of 7.1 years (range: 3 months to 15.8 years) developed tumor lysis syndrome. The most common malignancies were B-precursor acute lymphoblastic leukemia (ALL) (45%) followed by non-Hodgkin lymphoma (NHL) and Wilms’ tumor (each 10.4%), respectively. They received normal saline intravenously at a rate of 4-5 L/m2/day in 24-48 hours prior to initiating chemotherapy. Plasma samples were drawn to detect uric acid, calcium, phosphate, potassium, creatinine and blood urea nitrogen (BUN) 4 hours before administering a single dose of IV rasburicase (0.2 mg/kg over 30 minute). Laboratory markers were evaluated again 4 and 24 hours after administering rasburicase. Results: All patients with diagnosis of TLS had significantly decreased uric acid levels following single dose of rasburicase except 1 patient (2.1%) (P<0.001). Mean plasma uric acid concentration before treatment was 10.0±4.2 mg/dL and 4 hours after treatment declined to 2.2±5.5 (P<0.001). Hyperphosphatemia was also detected in 43.7% of these 48 cases which significantly decreased to 16.7% (P=0.012). Plasma uric acid levels remained low one day after treatment. No side effects were detected.  Conclusion: Rasburicase is a safe and highly effective drug in children with hyperuricemia in the setting of malignancy at risk of developing TLS.