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 patients, as it has been shown to be effective in preventing and managing TLS 1.

Key Components of TLS Treatment

• Aggressive hydration with intravenous fluids at 2-3 L/m²/day to maintain high urine output (100-200 mL/hour) is crucial in preventing urate crystal formation in the kidneys 1.
• For hyperuricemia, rasburicase 0.1-0.2 mg/kg IV is recommended for severe cases or when uric acid levels exceed 8 mg/dL, while allopurinol 100-300 mg orally every 8 hours can be used for less severe cases 1.
• Electrolyte abnormalities require specific interventions, such as:
  • Hyperkalemia: calcium gluconate (1 ampule IV), insulin with glucose (10 units regular insulin with 50 mL of 50% dextrose), or sodium polystyrene sulfonate (15-30 g orally) 1.
  • Hyperphosphatemia: phosphate binders like calcium acetate (667 mg, 2-3 tablets with meals) 1.
  • Hypocalcemia: treatment should only be initiated if symptomatic 1.

Prevention and Management

• Prevention is crucial in high-risk patients and includes starting hydration and allopurinol 24-48 hours before chemotherapy, or rasburicase in high-risk patients 1.
• Nephrological consultation should be considered before starting therapy in cases with previous episodes of clinical TLS 1.
• Rasburicase should be administered at a dose of 0.20 mg/kg/day, infused over 30 minutes, with the first dose given at least four hours before the start of tumor-specific therapy, and continued for at least 3-5 days 1.
• Allopurinol should be administered orally at a dose of 100 mg/m² thrice daily (maximum 800 mg/day) 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.

Of the subset of 61 patients whose plasma uric acid level was elevated at baseline (≥8 mg/dL), plasma uric acid concentration was maintained by 4 hours for 72% of patients (44/61), by 24 hours for 80% of patients (49/61), by 48 hours for 92% of patients (56/61), by 72 hours for 98% of patients (60/61), and by 96 hours for 100% (61/61).

The major endpoint of this 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.

The treatment of tumolytic syndrome (also known as tumor lysis syndrome (TLS)) involves the use of rasburicase (IV) to reduce plasma uric acid levels.

• Rasburicase (IV) is effective in maintaining plasma uric acid concentration within normal limits in a significant proportion of patients.
• The uric acid response rate is higher with rasburicase (IV) compared to allopurinol.
• Clinical TLS is defined by changes in laboratory parameters and the occurrence of certain events within 7 days of treatment.
• Rasburicase (IV) is administered at a dose of 0.15 mg/kg/day or 0.2 mg/kg/day as a 30-minute infusion once daily 2.
• Allopurinol (IV) is administered at a dose of 200 mg/m2/day to 400 mg/m2/day intravenously, with a maximum dose of 600 mg/day 3.

From the Research

Treatment of Tumolytic Syndrome

The treatment of tumolytic syndrome, also known as tumor lysis syndrome (TLS), involves several key strategies to prevent and manage this oncologic emergency.

• Aggressive hydration to help prevent kidney damage and reduce the risk of acute renal failure 4, 5, 6, 7, 8
• Control of hyperuricemia with allopurinol and rasburicase treatment to prevent uric acid nephropathy 4, 6
• Close monitoring of electrolyte abnormalities, including hyperkalemia, hyperphosphatemia, and hypocalcemia 4, 5, 6, 7, 8
• Use of hypouricemic agents, such as rasburicase, to prevent and treat hyperuricemia 6
• Treatment of hyperkalemia with sodium polystyrene sulfonate, hypertonic glucose and insulin, loop diuretics, and bicarbonate 6
• Treatment of hyperphosphatemia with dietary phosphate restriction and phosphate binders, such as aluminum hydroxide and aluminum carbonate 6
• Management of hypocalcemia with continuous intravenous infusion of calcium gluconate 6
• Consideration of hemodialysis for patients with excessively elevated uric acid, phosphate, and/or potassium, and those with acute renal failure 6

Prevention

Prevention is the most important aspect of TLS management, and involves:

• Risk assessment to identify patients at high risk of developing TLS 4, 5, 7, 8
• Prophylactic measures, such as aggressive hydration and use of hypouricemic agents, to prevent TLS in high-risk patients 4, 5, 7, 8
• Close monitoring of patients for signs and symptoms of TLS, including hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia 4, 5, 7, 8