What is the treatment for tumor lysis syndrome (TLS)?

From the Guidelines

The treatment of tumor lysis syndrome (TLS) should focus on aggressive hydration, electrolyte management, and uric acid reduction, with rasburicase being the preferred agent for high-risk cases due to its rapid reduction of uric acid levels 1.

Overview of TLS Treatment

The management of TLS involves several key components, including:

• Aggressive hydration to maintain high urine output and clear uric acid and phosphate
• Electrolyte management to address abnormalities such as hyperkalemia, hyperphosphatemia, and hypocalcemia
• Uric acid reduction using agents like allopurinol or rasburicase

Hydration and Electrolyte Management

Intravenous fluids should be administered at 2-3 L/m²/day to maintain high urine output (100-200 mL/hour), which helps clear uric acid and phosphate. Electrolyte abnormalities require specific management:

• Hyperkalemia may need insulin with glucose, calcium gluconate, sodium bicarbonate, or potassium binders
• Hyperphosphatemia requires phosphate binders like aluminum hydroxide (300-600 mg orally with meals)
• Hypocalcemia should only be treated if symptomatic

Uric Acid Reduction

For established TLS or high-risk cases, rasburicase (0.1-0.2 mg/kg IV as a single dose) is preferred due to its rapid reduction of uric acid levels by converting it to allantoin 1. Allopurinol (100-300 mg orally every 8 hours, or 200-400 mg/m²/day in children) can be used for prophylaxis, started 24-48 hours before chemotherapy to prevent uric acid formation.

Severe Cases and Hemodialysis

Severe cases with acute kidney injury may require hemodialysis, particularly with potassium >6 mEq/L, phosphorus >10 mg/dL, or symptomatic hypocalcemia. The decision to initiate hemodialysis should be made on a case-by-case basis, considering the patient's overall clinical condition and the severity of the metabolic abnormalities.

Prevention and Risk Stratification

Prevention of TLS is crucial, and risk stratification can help identify patients who require aggressive prophylaxis. Hydration and rasburicase should be administered to adult cancer patients who are candidates for tumor-specific therapy and who carry a high risk of TLS 1. Cancer patients with a low-risk of TLS should receive hydration along with oral allopurinol.

Clinical Guidelines and Recommendations

The management of TLS should be guided by clinical guidelines and recommendations, which emphasize the importance of aggressive hydration, electrolyte management, and uric acid reduction. The best management of TLS is prevention, and prophylaxis should be tailored to the individual patient's risk level 1.

From the FDA Drug Label

Tumor Lysis Syndrome (TLS) Clinical TLS was defined by changes in at least two or more laboratory parameters for hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia and at least one of the following events occurring within 7 days of treatment: renal failure/injury, need for renal dialysis, and/or serum creatinine increase >1.5 ULN, arrhythmia or seizure. Clinical TLS occurred in 3% of Elitek-treated patients, 3% of Elitek/allopurinol-treated patients, and 4% of allopurinol-treated patients.

Treatment of Tumor Lysis Syndrome (TLS): Rasburicase (Elitek) is used to treat TLS. The response rate in patients treated with Elitek was significantly greater than in those treated with allopurinol.

• Key findings:
  • Clinical TLS occurred in 3% of Elitek-treated patients.
  • The response rate in arm A (Elitek) was significantly greater than in arm C (allopurinol) (p=0.0009).
• Dosing: Elitek was administered at a dose of 0.2 mg/kg/day as a 30-minute infusion once daily.
• Efficacy: The major endpoint of the study was the uric acid response rate, defined as the proportion of patients with plasma uric acid levels ≤7.5 mg/dL from day 3 to day 7, after initiation of antihyperuricemic treatment. 2

From the Research

Treatment of Tumor Lysis Syndrome

The treatment of tumor lysis syndrome (TLS) involves several key components, including:

• Aggressive intravenous hydration to help clear high plasma levels of potassium, uric acid, and phosphorus 3, 4, 5, 6, 7
• Electrolyte management, such as the use of sodium polystyrene sulfonate, hypertonic glucose and insulin, loop diuretics, and bicarbonate to treat hyperkalemia 4, 5, 6
• The use of hypouricemic agents, such as allopurinol or rasburicase, to lower uric acid levels and prevent uric acid nephropathy 4, 5, 6, 7
• Phosphate binders, such as aluminum hydroxide and aluminum carbonate, to reduce dietary phosphate intake and treat hyperphosphatemia 4, 5, 6
• Continuous intravenous infusion of calcium gluconate to treat recurrent hypocalcemia 4, 5
• Hemodialysis or renal replacement therapy (RRT) in severe cases, such as excessively elevated uric acid, phosphate and/or potassium, or acute renal failure 4, 5, 6

Prevention of Tumor Lysis Syndrome

Prevention of TLS is critical, and involves:

• Identifying patients with risk factors for TLS development and implementing adequate preventive measures 3, 6, 7
• Vigilant laboratory and clinical monitoring 3, 6, 7
• Vigorous IV hydration 3, 6, 7
• Urate-lowering therapy 3, 6, 7
• Avoidance of exogenous potassium 6
• Use of phosphate binders 6
• Considering cytoreduction before the start of aggressive agent or a gradual escalation of its dose in high-risk cases 6