What is the management approach for Tumor Lysis Syndrome (TLS)?

Management of Tumor Lysis Syndrome (TLS)

Aggressive hydration, rasburicase administration, and electrolyte management form the cornerstone of TLS management, with early nephrology consultation and potential dialysis for severe cases. 1

Risk Assessment and Prevention

Risk Stratification

• Host-related factors:

  • Dehydration
  • Pre-existing renal impairment
  • Obstructive uropathy
  • Hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults) 2

• Disease-related factors:

  • Bulky disease (especially SCLC or massive liver metastases)
  • High-grade lymphomas (particularly Burkitt's lymphoma)
  • Acute lymphoblastic leukemia
  • Elevated LDH (>2× upper normal limit) 2, 1

• Therapy-related factors:

  • Intensive polychemotherapy with cisplatin, cytarabine, etoposide, methotrexate 2

Pre-Treatment Evaluation

1. Assess creatinine clearance (or estimated GFR)
2. Measure serum LDH levels
3. Obtain renal ultrasound in patients undergoing chemotherapy 2

Management Protocol

1. Hydration

• Start hydration 48 hours before chemotherapy when possible 2
• Maintain urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 2, 1
• Use IV normal saline at 75-100 mL/hr 1
• Loop diuretics may be required to maintain urine output (avoid in obstructive uropathy or hypovolemia) 2

2. Hyperuricemia Management

• High-risk patients:

  • Administer rasburicase 0.20 mg/kg/day IV over 30 minutes
  • Start ≥4 hours before chemotherapy
  • Continue for 3-5 days 2, 3
  • Rasburicase reduces uric acid levels to ≤2 mg/dL in 96% of patients within 4 hours 3

• Low-risk patients:

  • Allopurinol 100 mg/m² three times daily (maximum 800 mg/day) 2
  • Do not administer allopurinol concurrently with rasburicase 2

• Contraindications to rasburicase:

  • G6PD deficiency
  • Metahemoglobinemia
  • Other metabolic disorders that can cause hemolytic anemia 2, 1

3. Electrolyte Management

• Hyperkalemia:

  • Mild (<6 mmol/L): Hydration, loop diuretics, sodium polystyrene (1 g/kg orally or by enema)
  • Severe: Insulin (0.1 units/kg) plus glucose (25% dextrose 2 mL/kg), calcium gluconate (100-200 mg/kg), sodium bicarbonate
  • Continuous ECG monitoring for hyperkalemic patients 2

• Hypocalcemia:

  • Asymptomatic: No treatment required
  • Symptomatic (tetany, seizures): Calcium gluconate 50-100 mg/kg 2

• Hyperphosphatemia:

  • Phosphate binders (e.g., aluminum hydroxide)
  • Obtain nephrology consultation for persistent elevation 1

4. Monitoring

• Monitor uric acid, phosphate, potassium, creatinine, calcium, and LDH every 12 hours for first 3 days, then every 24 hours 1
• Continuous evaluation of fluid input and urine output 1
• ECG monitoring in patients with electrolyte abnormalities 2

Indications for Renal Replacement Therapy

Immediate dialysis is indicated for:

• Persistent hyperkalemia unresponsive to medical management
• Severe metabolic acidosis
• Volume overload unresponsive to diuretic therapy
• Overt uremic symptoms (pericarditis, severe encephalopathy)
• Severe progressive hyperphosphatemia (>6 mg/dL)
• Severe symptomatic hypocalcemia 2

Dialysis considerations:

• Frequent (daily) dialysis is recommended due to continuous release of metabolites 2
• Hemodialysis reduces plasma uric acid by approximately 50% with each 6-hour treatment 2
• Continuous renal replacement therapies (CRRT) may be preferred in hemodynamically unstable patients 2

Special Considerations

• Avoid all nephrotoxic medications (NSAIDs, certain antibiotics) 1
• High-risk patients should only receive chemotherapy in facilities with ready access to dialysis 1
• Urine alkalinization is not recommended in patients receiving rasburicase 2
• Obtain immediate nephrology consultation for inadequate urine output or severe electrolyte abnormalities 1

Treatment Setting

• High-risk patients should be managed in an inpatient setting with access to dialysis 2, 1
• Low-risk patients can be managed with oral allopurinol, hydration, and urine alkalinization 2

TLS management requires vigilant monitoring and aggressive intervention to prevent life-threatening complications including acute renal failure, cardiac arrhythmias, and seizures.