Comparative evaluation of single fixed dosing and weight-based dosing of rasburicase for tumor lysis syndrome.

STUDY OBJECTIVE: To evaluate single fixed dosing versus weight-based dosing strategies for rasburicase to determine the minimum dose required to mitigate hyperuricemia in the treatment or prevention of tumor lysis syndrome. DESIGN: Retrospective medical record review SETTING: Academic medical center PATIENTS: A total of 373 patients with a diagnosis of a hematologic malignancy or solid tumor and who received at least one dose of rasburicase over a 6-year period between January 1, 2005, and February 18, 2011; 180 patients received single doses of 3 mg (38 patients), 6 mg (99 patients), or 7.5 mg (43 patients), and 193 patients received weight-based dosing. MEASUREMENTS AND MAIN RESULTS: Tumor lysis syndrome laboratory data were recorded at baseline and monitored up to 72 hours after initial rasburicase administration. Median baseline plasma uric acid levels were 6.85 mg/dl, 8.80 mg/dl, 8.00 mg/dl, and 9.20 mg/dl, respectively, in the 3-mg, 6-mg, 7.5-mg, and weight-based dosing groups. Treatment success was defined as a normalized plasma uric acid level (< 7.5 mg/dl) within 24 hours after receiving rasburicase. The mean weight-based dose was 0.16 mg/kg. Six rasburicase treatment failures occurred; two were in the 3-mg group, one was in the 6-mg group, and three were in the weight-based dosing group. At 24 hours after rasburicase administration, no statistically significant differences in treatment success were noted among groups (92.9% vs 97.6% vs 100.0% vs 98.0% in the 3-mg, 6-mg, 7.5-mg, and weight-based dosing groups, respectively, p=0.1238). CONCLUSION: The efficacy of all single fixed doses and weight-based dosing strategies evaluated in this study appear to be comparable in normalizing plasma uric acid levels within 24 hours of rasburicase administration. Although use of a 3-mg rasburicase dose may be the most cost-effective treatment strategy in managing hyperuricemia secondary to tumor lysis syndrome, the 6-mg dose resulted in lower sustained uric acid levels after rasburicase administration. Further analysis of patient specific factors contributing to the need for repeat rasburicase administration should be conducted in larger, prospective clinical trials.

Higher urinary excretion of inorganic phosphate during early induction chemotherapy predicts a good prognosis in childhood acute leukemia.

The rapidity of response to induction therapy is emerging as an important prognostic factor in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Urine inorganic phosphate (IP) and uric acid (UA) may increase in patients with acute leukemia who undergo their induction chemotherapy, owing to the breakdown of tumor cells. The crystallization of UA or calcium phosphate in renal tubules can result in acute tumor lysis syndrome (ATLS). Some reports indicate that patients who experience ATLS have a better prognosis than those who do not. We investigated the relationship between urinary IP and UA excretion and treatment outcome in children with acute leukemia. Participants included 93 patients with ALL and 31 patients with AML. Urine samples were collected and measured for the first 3 days of induction chemotherapy. Among patients with ALL, urinary IP excretion was significantly higher in patients without relapse than in those with relapse and correlated with long-term outcome. Among patients with AML, urinary IP excretion was significantly higher in patients without induction failure (IF) than those with IF. We propose that higher urinary IP excretion could be a useful prognostic marker for determining favorable outcomes in patients with acute leukemia.

Treatment of tumor lysis syndrome with the highest known uric acid level.

Tumor lysis syndrome (TLS) is a disease with high mortality that develops in conditions characterized by rapid cell proliferation or after the cytotoxic treatment of malignant diseases. Extraction of intracellular ions and metabolites into the extracellular milieu following cell destruction causes hyperuricemia, hyperphosphatemia, hypocalcemia, hyperkalemia, and uremia. The prophylaxis and treatment of TLS includes intensive hydration, diuretics, alkalinization of the urine, allopurinol, and rasburicase. Close electrolyte monitoring of the patients is required. In the patients with acute renal failure (ARF), dialysis can be used either as the first treatment of choice or together with the above-mentioned prophylactic and therapeutic agents. Herein we report the effective treatment of a patient with anuric ARF by means of sequential hemodialysis sessions, in whom TLS developed after chemotherapy; the uric acid level was 71.3 mg/dL, which was considerably greater than the values reported in the literature.

Inability to alkalinize urine in a patient at risk for tumor lysis syndrome: a case report.

This report provides a description and discussion of a 19-year-old, 65-kg male, with a large mediastinal mass, right pleural effusion, and pericardial effusion, requiring urine alkalinization during a propofol infusion. The patient required NaHCO3 boluses, urine pH, electrolyte, arterial blood gas and lactate monitoring, and discontinuation of the propofol. The authors suggest that caution be used when prescribing a propofol infusion for patients who are at risk of tumor lysis syndrome and the need for urine alkalinization.

Avoiding dialysis in tumour lysis syndrome: is urate oxidase effective? - a case report and review of literature.

INTRODUCTION: Hyperuricaemia in tumour lysis syndrome (TLS) can cause acute renal failure (ARF), necessitating dialysis. Recombinant urate oxidase (rasburicase) converts uric acid to soluble allantoin, which is excreted easily. CASE REPORT: An 8-year-old boy with stage 3 Burkitt's lymphoma, TLS was successfully treated with hyper-hydration, diuretics and rasburicase, without dialysis. This is the first paediatric case in Kandang Kerbau Women's & Children's Hospital (KKH) in which rasburicase was used. We review the literature on the effectiveness of urate oxidase in avoiding dialysis in TLS. TREATMENT AND OUTCOME: Our patient developed rapidly rising serum uric acid (SUA) and progressive renal impairment. Hyper-hydration and rasburicase (0.2mg/kg) were administered. SUA rapidly decreased from 1308 to 437 mmol/L within 12 hours. Urate oxidase has shown better results than allopurinol. There was a need for dialysis in 0.4% to 1.7% of patients with haematological malignancies given rasburicase, compared to 20% in patients given allopurinol. CONCLUSIONS: Rasburicase can reverse renal insufficiency. Though expensive, it may be cost-effective by lowering incidence of dialysis, shortening the duration of intensive care and hospitalisation, allowing early chemotherapy.

Recurrent chemotherapy-induced tumor lysis syndrome (TLS) with renal failure in a patient with chronic lymphocytic leukemia - successful treatment and prevention of TLS with low-dose rasburicase.

INTRODUCTION: Rasburicase is a recombinant urate oxidase that is produced by a genetically modified Saccharomyces cerevisiae and has been approved for prophylaxis and treatment of tumor lysis syndrome in 2001. In several studies, rasburicase, given at a dose of 0.15-0.2 mg/kg for up to 7 d, proved to be highly effective in lowering urate levels. CASE REPORT: We report the case of a patient with chronic lymphatic leukemia (CLL) who experienced tumor lysis syndrome (TLS) with acute renal failure after fludarabine/cyclophosphamide chemotherapy and after bendamustine treatment. During the first episode of TLS, after fludarabine/cyclophosphamide (creatinine 3.3 mg/dL, urate 24.6 mg/dL), the patient received rasburicase 0.2 mg/kg for 3 d. Urate levels decreased below the lower limit of normal and renal function recovered. After bendamustine therapy, given for disease progression 8 months later, TLS with acute oliguric renal failure re-occurred (creatinine 3.1 mg/dL, urate 20.8 mg/dL). The patient was treated with hyperhydration and two doses of rasburicase (0.056 mg/kg), resulting in a prompt decrease of the urate level and recovery of renal function. Both episodes of TLS were successfully treated with rasburicase in a lower dose than recommended by the manufacturer. During a second bendamustine course, TLS was successfully treated by low doses of rasburicase (0.056 mg/kg for 2 d). CONCLUSION: This is the first report of TLS in CLL after bendamustine chemotherapy reported in the literature. Treatment and prevention of TLS by low doses of rasburicase is possible and cost-effective.

A tumor lysis-like syndrome during therapy of visceral leishmaniasis.

Reported herein for the first time in the literature is the case of a 41-yr-old woman who developed a tumor lysis-like syndrome, consisting of hyperkalemia, hyperphosphatemia, hyperuricemia, and acute renal insufficiency, soon after the initiation of chemotherapy for severe visceral leishmaniasis with liposomal amphotericin B. Allopurinol therapy, together with iv fluid administration and urine alkalization, resulted in full recovery of the metabolic abnormalities. Awareness of this condition can lead to prophylactic treatment as well as the early recognition and management of susceptible patients.