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

What is known and objectiveTo perform a meta-analysis exploring the optimal single-dose regimen for managing tumour lysis syndrome (TLS) in children and adults with haematological malignancies. MethodsWe 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. ResultsFifteen 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 15, 3, 45, 6, 75 mg and weight-based single doses of 005 and 015 mg/kg were compared. The response rate for 6, 75 mg and 015 mg/kg single doses was 90% (95% CI: 0825-0974), 986% (95% CI: 0957-1015) and 936% (95% CI: 0864-1007), respectively, and higher than other dosing regimens tested. The single doses of 6 mg and 015 mg/kg rasburicase decreased uric acid levels more than the other regimens, and the mean uric acid reduction was 845 mg/dL (95% CI, 751-938) and 10 mg/dL (95% CI, 858-1142), respectively. What is new and conclusionOur 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 45-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 15 mg and 015 mg/kg single dose were sufficient to manage TLS in children.