Tumour Lysis Syndrome: Prophylaxis and Management
For high-risk patients receiving cytotoxic therapy, administer aggressive IV hydration plus prophylactic rasburicase to prevent tumour lysis syndrome, as prevention is far superior to treatment and can prevent life-threatening complications including acute kidney injury, cardiac arrhythmias, and death. 1
Risk Stratification is Critical
Before initiating cytotoxic therapy, you must stratify patients into risk categories based on tumour type, burden, and patient factors:
High-risk patients include those with:
- Acute lymphoblastic leukemia (ALL) or Burkitt's lymphoma
- High tumour burden or proliferative rate
- Elevated baseline uric acid, LDH, or creatinine
- WBC count >200,000/μL with renal dysfunction 2
Intermediate-risk patients have moderate tumour burden or less aggressive malignancies.
Low-risk patients require only close monitoring.
Prophylaxis Strategy by Risk Level
High-Risk Patients
Initiate hydration at least 48 hours before chemotherapy when possible (though rasburicase allows earlier treatment if urgent). 1, 3
- IV hydration: Maintain urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg)
- Rasburicase: Prophylactic administration is the standard for high-risk patients 1
- Loop diuretics: Add if needed to maintain urine output (avoid in obstructive uropathy or hypovolemia) 3
Intermediate-Risk Patients
- IV hydration plus either allopurinol OR rasburicase 1
- Allopurinol dosing: 100 mg/m² three times daily (maximum 800 mg/day) 3
Low-Risk Patients
- Close monitoring only 1
Critical Caveats About Rasburicase
Do NOT use rasburicase in patients with:
- G6PD deficiency (causes hemolytic anemia)
- Methemoglobinemia
- Other metabolic disorders predisposing to hemolysis 3
For these patients, use allopurinol with hydration instead.
Never give allopurinol concurrently with rasburicase - this causes xanthine accumulation and eliminates rasburicase substrate. 3
Alkalinization: Abandoned Practice
Do NOT alkalinize urine, particularly in patients receiving rasburicase. 1, 3 While historically used to increase uric acid solubility, alkalinization:
- Increases calcium phosphate precipitation
- Reduces xanthine solubility
- Provides no advantage in correcting biochemical abnormalities
This represents an important shift from older practice patterns.
Monitoring Protocol
High-Risk Patients (Before TLS Develops)
Monitor every 12 hours for first 3 days, then every 24 hours: 3
- Uric acid, LDH
- Electrolytes (potassium, phosphorus, calcium, sodium)
- Renal function (creatinine, BUN)
Established TLS
Monitor every 6 hours for first 24 hours, then daily: 3
- Vital signs (heart rate, blood pressure, urine output, respiratory rate)
- Serum uric acid
- Electrolytes (phosphate, calcium, potassium)
- Renal function (creatinine, BUN, urine pH, osmolality, specific gravity)
- ECG monitoring for hyperkalemia
- Daily: CBC, LDH, albumin, blood gases, body weight
Management of Established TLS
Clinical TLS is an emergency requiring immediate aggressive intervention. 3
Core Treatment
- Central venous access for hydration
- Rasburicase (same contraindications as prophylaxis)
- Aggressive IV hydration targeting urine output ≥100 mL/hour
- Loop diuretics or mannitol if needed to maintain output 3
Electrolyte Management
Hyperkalemia:
- Mild (<6 mmol/L): Hydration, loop diuretics, sodium polystyrene 1 g/kg
- Severe: Insulin 0.1 units/kg + 25% dextrose 2 mL/kg, calcium carbonate 100-200 mg/kg, sodium bicarbonate for acidosis
- Continuous ECG monitoring mandatory 3
Hyperphosphatemia:
- Mild (<1.62 mmol/L): May not require treatment
- Moderate-severe: Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses 3
Hypocalcemia:
- Asymptomatic: Do NOT treat (increases calcium phosphate precipitation) 3
- Symptomatic (tetany, seizures): Calcium gluconate 50-100 mg/kg single dose, repeat cautiously if needed 3
When to Initiate Dialysis
Consider early renal replacement therapy (RRT) for: 4
- Severe hyperkalemia unresponsive to medical management
- Severe hyperphosphatemia
- Metabolic acidosis
- Fluid overload unresponsive to diuretics
The threshold for RRT in TLS is lower than other conditions because cell breakdown is ongoing and electrolyte levels can rise unpredictably. 4 High-risk patients should receive chemotherapy only in facilities with ready dialysis access and nephrology consultation. 4
Real-World Evidence
Despite optimal prophylaxis, breakthrough TLS can occur. Recent data shows that even with low-dose rasburicase prophylaxis achieving 92% urate normalization within 24 hours, 14% of prophylaxis patients still developed clinical TLS, with 64% having pre-existing kidney impairment. 5 This emphasizes that patients with baseline renal dysfunction require especially vigilant monitoring even with appropriate prophylaxis.
The evidence strongly supports that allopurinol alone is insufficient for high-risk patients, particularly those with WBC >200,000/μL and renal dysfunction at diagnosis. 2