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

Treatment of Tumor Lysis Syndrome

For established clinical TLS, immediately initiate aggressive IV hydration through central venous access at ≥2 L/m²/day targeting urine output ≥100 mL/hour (3 mL/kg/hour in children <10 kg), combined with rasburicase 0.20 mg/kg/day IV over 30 minutes for 3-5 days, followed by transition to oral allopurinol—never administer these agents concurrently. 1, 2, 3

Immediate Fluid Resuscitation

• Aggressive hydration is the cornerstone of TLS treatment, requiring at least 2 L/m²/day through central venous access to enhance renal blood flow, improve glomerular filtration, and promote urinary excretion of uric acid and phosphate 1
• Target urine output must be maintained at ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 1, 3
• Loop diuretics (or mannitol) may be required to maintain adequate urine output, except in patients with obstructive uropathy or hypovolemia 1, 3
• Hydration should ideally begin 48 hours before chemotherapy when possible, though rasburicase allows earlier treatment initiation if clinically necessary 1, 3

Pharmacologic Management of Hyperuricemia

Rasburicase as First-Line for Clinical TLS

• Rasburicase is mandatory for all patients with clinical TLS and should be administered at 0.20 mg/kg/day IV over 30 minutes for 3-5 days 1, 2, 4
• Rasburicase converts existing uric acid to allantoin, which is 5-10 times more soluble than uric acid, providing immediate reduction of pre-existing hyperuricemia 2
• In FDA trials, 96% of patients achieved uric acid levels ≤2 mg/dL within 4 hours of the first rasburicase dose 4
• Critical contraindications include G6PD deficiency, history of anaphylaxis to rasburicase, methemoglobinemia, hemolytic reactions, pregnancy, and lactation 2, 4

Transition to Allopurinol

• After completing 3-5 days of rasburicase, transition to oral allopurinol at 100 mg/m² every 8 hours (maximum 800 mg/day) or 200-400 mg/m²/day IV in divided doses (maximum 600 mg/day) 2
• Never administer rasburicase and allopurinol concurrently—this causes xanthine accumulation and potential xanthine crystal deposition in renal tubules 2
• Reduce allopurinol dose by 50% or more in patients with renal insufficiency due to drug and metabolite accumulation 2

Electrolyte Management

Hyperkalemia

• Mild asymptomatic hyperkalemia (<6 mmol/L): Correct with hydration, loop diuretics, and sodium polystyrene 1 g/kg orally or by enema 1, 3
• Severe hyperkalemia (≥6 mmol/L): Administer rapid insulin 0.1 units/kg plus glucose (25% dextrose 2 mL/kg), calcium carbonate 100-200 mg/kg/dose, and sodium bicarbonate to stabilize myocardial membranes and correct acidosis 1, 3
• Continuous ECG monitoring is mandatory in all hyperkalemic patients 1, 3

Hyperphosphatemia

• Mild hyperphosphatemia (<1.62 mmol/L): Treat with aluminum hydroxide 50-100 mg/kg/day divided in 4 doses, administered orally or via nasogastric tube 1, 3
• Severe hyperphosphatemia (>6 mg/dL) may require dialysis 3

Hypocalcemia

• Asymptomatic hypocalcemia requires no treatment 1, 3
• Symptomatic hypocalcemia (tetany, seizures): Administer calcium gluconate 50-100 mg/kg as a single IV dose, cautiously repeating if necessary 1, 3
• Avoid calcium administration in the presence of severe hyperphosphatemia due to risk of calcium-phosphate precipitation 1

Renal Replacement Therapy Indications

Initiate dialysis for any of the following absolute indications:

• Persistent hyperkalemia unresponsive to medical management 3
• Severe metabolic acidosis 3
• Volume overload unresponsive to diuretic therapy 3
• Overt uremic symptoms 3
• Severe progressive hyperphosphatemia (>6 mg/dL) 3
• Severe symptomatic hypocalcemia 3

Dialysis Modality Selection

• Intermittent hemodialysis (IHD) provides uric acid clearance of 70-100 mL/min, reducing plasma uric acid by approximately 50% with each 6-hour treatment 1, 3
• Daily hemodialysis is recommended due to continuous release of metabolites from lysed tumor cells 1, 3
• Continuous renal replacement therapy (CRRT) is preferred for hemodynamically unstable patients, providing better control of fluid overload and azotemia 3
• Peritoneal dialysis is rarely used due to lower efficiency compared to IHD and CRRT 3

Monitoring Requirements

High-Risk Patients

• Monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours for the first 3 days, then every 24 hours 3

Established TLS Patients

• Monitor vital signs, serum uric acid, electrolytes, and renal function every 6 hours for the first 24 hours, then daily 3
• Blood samples must be placed immediately on ice to prevent continued ex vivo enzymatic degradation by rasburicase, which falsely lowers measured uric acid levels 2, 4

Critical Pitfalls to Avoid

• Never delay rasburicase administration—the first dose must be given at least 4 hours before tumor-specific chemotherapy 2, 3
• Never co-administer rasburicase and allopurinol—this causes dangerous xanthine accumulation 2
• Never administer calcium in the presence of severe hyperphosphatemia—this precipitates calcium-phosphate crystals 1
• Never use loop diuretics in patients with obstructive uropathy or hypovolemia 1, 3
• Never fail to screen for G6PD deficiency before rasburicase administration—this causes life-threatening hemolysis 2, 4
• Inadequate hydration that fails to maintain target urine output of ≥100 mL/hour prevents effective crystallization prevention 3