What is the management of tumor lysis syndrome?

Management of Tumor Lysis Syndrome

Hydration through a central venous access and rasburicase should be administered to all patients with clinical tumor lysis syndrome (TLS). 1

Risk Assessment and Prevention

• TLS is a potentially life-threatening complication of massive cellular lysis in rapidly proliferating, bulky, or highly chemo-radiosensitive cancers 1
• High-risk patients include those with:
  • Host-related factors: dehydration, hyponatremia (in solid tumors), pre-existing renal impairment, obstructive uropathy, hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults) 1
  • Disease-related factors: bulky disease, high-grade lymphomas (particularly Burkitt's lymphoma), acute lymphoblastic leukemia, elevated LDH (>2 upper normal limit) 1
  • Therapy-related factors: intensive polychemotherapy including cisplatin, cytosine arabinoside, etoposide, methotrexate 1

Treatment Algorithm

For Clinical TLS

1. Aggressive hydration:

   • Start hydration 48 hours before tumor-specific therapy when possible 1
   • Maintain urine output at ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 1
   • Loop diuretics may be required except in patients with obstructive uropathy or hypovolemia 1

2. Rasburicase administration:

   • Administer at 0.20 mg/kg/day, infused over 30 minutes 1
   • First dose should be given at least four hours before starting tumor-specific therapy 1
   • Continue for 3-5 days 1
   • Contraindicated in patients with G6PDH deficiency or other metabolic disorders that can cause hemolytic anemia 1

3. Management of electrolyte abnormalities:

   • Hyperphosphatemia (<1.62 mmol/L): Treat with aluminum hydroxide at 50-100 mg/kg/day divided in 4 doses 1
   • Hypocalcemia: Only treat if symptomatic with calcium gluconate 50-100 mg/kg 1
   • Hyperkalemia:
     • Mild (<6 mmol/L): Hydration, loop diuretics, sodium polystyrene 1 g/kg 1
     • Severe: Insulin (0.1 units/kg) plus glucose (25% dextrose 2 mL/kg), calcium carbonate 100-200 mg/kg/dose, sodium bicarbonate 1
     • Continuous ECG monitoring for hyperkalemic patients 1

For Laboratory TLS

• Same approach as clinical TLS for adults 1
• For children, rasburicase is indicated if they are high-risk or show rapid worsening of biochemical parameters 1

For TLS Prevention

• High-risk patients: Rasburicase and hydration 1
• Low-risk patients: Oral allopurinol (100 mg/m² thrice daily, maximum 800 mg/day), hydration 1

Monitoring

• High-risk patients (pre-treatment): Monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours for the first three days, then every 24 hours 1
• Patients with TLS: Monitor every 6 hours for the first 24 hours, then daily:
  • Vital parameters (heart rate, blood pressure, urine output, respiratory rate)
  • Serum uric acid, electrolytes (phosphate, calcium, potassium)
  • Renal function (creatinine, BUN, urine pH and osmolality, urine specific gravity) 1
  • Daily monitoring of blood cell count, serum LDH, albumin, serum osmolality, blood gases, acid-base equilibrium, ECG, and body weight 1

Dialysis Indications

• Indications for renal replacement therapy include:
  • Severe oliguria or anuria
  • Persistent hyperkalemia
  • Hyperphosphatemia with symptomatic hypocalcemia
  • Hyperuricemia not responding to rasburicase
  • Severe volume overload 1
• Hemodialysis can reduce plasma uric acid levels by approximately 50% with each 6-hour treatment 1

Important Considerations

• Urine alkalinization is not recommended in patients receiving rasburicase therapy 1
• Calcium gluconate should not be used to correct mild hypocalcemia as it may lead to increased tissue and renal precipitation of calcium phosphate 1
• Rasburicase allows for earlier administration of chemotherapy due to rapid degradation of uric acid 1, 2
• Do not administer allopurinol concurrently with rasburicase to avoid xanthine accumulation and lack of substrate for rasburicase 1