What is the treatment for Tumor Lysis Syndrome (TLS)?

Treatment of Tumor Lysis Syndrome

The treatment of tumor lysis syndrome (TLS) requires aggressive hydration through a central venous access and administration of rasburicase to all patients with clinical TLS, along with management of specific electrolyte abnormalities and consideration of dialysis for severe cases. 1

Initial Management

• Aggressive hydration should be initiated, ideally 48 hours before tumor-specific therapy when possible, with a goal of maintaining urine output at ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 1, 2
• Rasburicase should be administered at 0.20 mg/kg/day, infused over 30 minutes, with the first dose given at least four hours before starting tumor-specific therapy 1
• Rasburicase treatment should continue for 3-5 days, as it rapidly and effectively reduces hyperuricemia 1, 2
• Loop diuretics (or mannitol) may be required to maintain adequate urine output, except in patients with obstructive uropathy or hypovolemia 1

Management of Specific Electrolyte Abnormalities

Hyperuricemia

• Rasburicase is superior to allopurinol for treating hyperuricemia in TLS, as demonstrated by significantly lower serum uric acid levels and area under the curve measurements 1
• Allopurinol (100 mg/m² thrice daily, maximum 800 mg/day) should be used in patients with contraindications to rasburicase, such as G6PD deficiency or metahemoglobinemia 1, 2

Hyperphosphatemia

• Mild hyperphosphatemia (<1.62 mmol/L) may not require treatment 1
• For higher levels, aluminum hydroxide at 50-100 mg/kg/day divided in 4 doses can be administered orally or by nasogastric tube 1

Hypocalcemia

• Asymptomatic hypocalcemia does not require treatment 1, 2
• For symptomatic hypocalcemia (tetany, seizures), administer calcium gluconate 50-100 mg/kg as a single dose, cautiously repeating if necessary 1
• Avoid calcium supplementation in asymptomatic patients as it may increase calcium phosphate precipitation in tissues 2

Hyperkalemia

• Mild (<6 mmol/L) asymptomatic hyperkalemia: treat with hydration, loop diuretics, and sodium polystyrene 1 g/kg orally or by enema 1
• Severe hyperkalemia: administer rapid insulin (0.1 units/kg) plus glucose (25% dextrose 2 mL/kg), calcium carbonate 100-200 mg/kg/dose, and sodium bicarbonate 1
• Perform careful ECG monitoring in all hyperkalemic patients 1

Indications for Dialysis

• Persistent hyperkalemia despite medical management 1
• Severe metabolic acidosis 1
• Volume overload unresponsive to diuretic therapy 1
• Overt uremic symptoms, including pericarditis and severe encephalopathy 1
• Severe, progressive hyperphosphatemia (>6 mg/dL) or symptomatic hypocalcemia 1
• Oliguria or anuria due to acute uric acid nephropathy 1, 2

Monitoring

• High-risk patients: monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours for the first three days, then every 24 hours 1, 2
• Patients with established TLS: monitor vital parameters, serum uric acid, electrolytes, and renal function every 6 hours for the first 24 hours, then daily 1, 2

Important Considerations and Pitfalls

• Do not administer allopurinol concurrently with rasburicase to avoid xanthine accumulation and lack of substrate for rasburicase 1, 2
• Urine alkalinization is not recommended in patients receiving rasburicase therapy 1, 2
• Rasburicase is contraindicated in patients with G6PD deficiency or other metabolic disorders that can cause hemolytic anemia 1
• Hemodialysis can reduce plasma uric acid levels by approximately 50% with each 6-hour treatment and should be considered early in patients with renal failure 1, 3
• Continuous renal replacement therapies (CRRT) may be preferred over intermittent hemodialysis in hemodynamically unstable patients 1

By following this comprehensive approach to TLS management, focusing on aggressive hydration, rasburicase administration, electrolyte correction, and timely initiation of dialysis when indicated, mortality and morbidity from this oncologic emergency can be significantly reduced.