Is Rasburicase Effective In Reversing Acute Renal Failure In Patients with Tumor Lyses Syndrome?

Abstract 4939

Tumor lysis syndrome (TLS) is a potentially life-threatening complication that can occur spontaneously or following treatment of malignant neoplasms, particularly leukemias and lymphomas. TLS can cause acute renal failure (ARF) by precipitation of uric acid (UA) and phosphate crystals in renal tubules. Rasburicase, a recombinant urate oxidase, was proven to be effective in the treatment of TLS and is known to cause an improvement in renal function in a subset of patients with TLS. For the purposes of our analysis ARF was defined as more than 50% increase in creatinine from baseline value or presenting with creatinine more or equal to 2 mg/dl with no previous history of chronic renal failure. To assess the efficacy of Rasburicase in adult patients with documented TLS and ARF in improving or normalizing the creatinine clearance (CrCl), we conducted a retrospective analysis of 53 patients that received Rasburicase for documented TLS. 41 patients fit the inclusion criteria. The median age was 54 yr (26-90), 13 were female. The majority of patients had hematological malignancies (acute leukemia, 11; chronic leukemia, 5; myeloproliferative/myelodysplastic syndromes, 4; lymphoma or myeloma, 10; solid tumor; 11).

Results: On the first day of rasburicase infusion (day 0), median UA, creatinine and CrCl were 11.5 mg/dl (5.1 - 23.7mg/dl), 3.26 mg/dl and 32.5 ml/min (8.0 - 97.8 ml/min) calculated using Cockcroft-Gault equation, respectively. Patients received an average total dose of 0.17 mg/kg (0.06-0.51 mg/kg) of rasburicase in one or two doses. UA levels normalized in 97.3% and 100% of patients by day 2 and 7 respectively. Creatinine levels normalized in 19% and 59.4% by day 2 and 7 respectively. CrCl improved form a median of 32.5 ml/min to 40.5 ml/min and 58 ml/min by day 2 and 7 respectively. A sub analysis for patients with baseline CrCl <30 ml/min (n=17) on day 0 of Rasburicase infusion revealed a similar benefit to those with baseline CrCl >30 ml/min. CrCl improved in this subset of patients from a median of 17 ml/min (8-28.2 ml/min) to 24.5 and 47.4 ml/min on days 2 and 7 respectively. Patients who received a total dose of <0.1mg/kg of rasburicase (n=8) derived similar benefits to those who received 0.2mg/kg or more (n=11).

Conclusion: Rasburicase infusion is effective in improving the creatinine clearance even in patients with advanced renal failure (CrCl<30 ml). Lower doses of Rasburicase are as effective as higher doses, even in patients with advanced renal failure, making the lower dose advisable and cost effective.