The optimal single-dose regimen of rasburicase for management of tumour lysis syndrome in children and adults: a systematic review and meta-analysis.

Abstract

To perform a meta-analysis exploring the optimal single-dose regimen for managing tumour lysis syndrome (TLS) in children and adults with haematological malignancies. We systematically searched PubMed, MEDLINE, Web of Science, the Cochrane Library and the ClinicalTrials.gov website for studies regarding single-dose rasburicase in paediatric and adult patients with TLS. Data were analysed using Open MetaAnalyst statistical software. Fifteen adult studies (fourteen retrospective studies and one randomized controlled trial) and four observational studies using children were extracted, with a total of 906 and 92 subjects, respectively. Single doses of 1·5, 3, 4·5, 6, 7·5 mg and weight-based single doses of 0·05 and 0·15 mg/kg were compared. The response rate for 6, 7·5 mg and 0·15 mg/kg single doses was 90% (95% CI: 0·825-0·974), 98·6% (95% CI: 0·957-1·015) and 93·6% (95% CI: 0·864-1·007), respectively, and higher than other dosing regimens tested. The single doses of 6 mg and 0·15 mg/kg rasburicase decreased uric acid levels more than the other regimens, and the mean uric acid reduction was 8·45 mg/dL (95% CI, 7·51-9·38) and 10 mg/dL (95% CI, 8·58-11·42), respectively. Our meta-analysis revealed that, for adult patients, a single 6 mg rasburicase dose is sufficient to normalize and sustain lower uric acid and creatinine levels in adults with TLS. This dose, therefore, balances cost and efficacy of treatment. The 3- and 4·5-mg single dose can be considered if the baseline uric acid level <12 mg/dL, with close monitoring of clinical and biochemical parameters, and repeat dosing if required. The 1·5 mg and 0·15 mg/kg single dose were sufficient to manage TLS in children.