Successful Treatment of Tumor Lysis Syndrome (TLS) with Low Doses of Rasburicase in Patients with Impaired Renal Function (IRF).
Authors: Hummel Margit , Buchheidt Dieter , Ulm Silke , Reiter Sebastian , Hehlmann Rudiger 
Published: April 2020

Abstract
Background: TLS commonly occurs in patients with hematologic malignancies and is characterized by elevation of uric acid, potassium and phosphate and by hypocalcemia. A major complication is renal failure caused by precipitation of uric acid and / or calcium phosphate crystals. Standard treatment consists of hydration, correction of electrolyte disturbances and lowering of uric acid. Rasburicase, a recombinant urate oxidase, has proven to be highly effective in lowering serum uric acid levels, and its application is not restricted in patients with renal failure. Costs for a full seven-day course of rasburicase in the dosage recommended are high and amount to approximately 4800 €.
Our question was whether patients with TLS and IRF can be treated cost-effectively with low doses of rasburicase.
Patients and Methods: 26 patients (16 male, median age 65 yrs, range 16–76) with TLS and IRF were treated with 1–5 doses of rasburicase. Median number of rasburicase doses was 1, the median total dose given was 3 mg (range 1–15 mg) (0,038 mg/kg, range 0,016–0,19 mg/kg). 5 patients had acute leukemia, 13 had lymphoma, 5 had myeloproliferative disease and 3 had solid tumors. In 17 patients TLS was chemotherapy-induced, whereas 9 patients had spontaneous TLS. 10/26 patients had pre-existing chronic renal failure.
TLS was classified and graded according to Cairo and Bishop. Laboratory TLS was diagnosed in 3 patients, 23 patients had clinical TLS (grade 1: n = 2, grade 2: n = 12, grade 3: n = 8, grade 4: n = 1).
Results: The mean uric acid level before rasburicase administration was 15,35 mg/dl (range 10–22,2 mg/dl), the mean creatinine level was 3,29 mg/dl (range 1,41–8,61 mg/dl). The median rasburicase dose applied was 3,2 % of the dose recommended by the manufacturer (0,2 mg/kg for 5–7 days). Rasburicase was well tolerated by all patients without side effects. The mean serum uric acid level after rasburicase was 3,45 mg/dl (range 0,1–13 mg/dl). In 5 patients uric acid was above the upper limit of normal after rasburicase treatment; 3 of these patients had progressive malignant disease and died of disease progression, 2 of these patients had pre-existing chronic renal failure. Serum creatinine was within the normal range after rasburicase treatment in 16/26 patients. Of those patients without normalization of creatinine, 4 had progressive malignant disease and 5 had pre-existing chronic renal failure. No patient required renal replacement therapy.
Conclusion: Treatment with low doses of rasburicase is effective in patients with TLS and IRF. Serum uric acid levels can be lowered effectively and renal function is improved in the majority of patients. Treatment costs can be reduced considerably (from 4800 € to approximately 160 €) by administering low doses of rasburicase. The effectiveness of low dose rasburicase was limited in patients with progressive malignant disease and ongoing tumor lysis and in patients with pre-existing chronic renal failure. Prospective studies with a standardized protocol for rasburicase administration are required to establish specific dosage regimens for subgroups of patients and to optimize cost-effective treatment.