What is the management of tumor lysis syndrome?

Management of Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) management requires aggressive hydration starting 48 hours before tumor-specific therapy, rasburicase administration at 0.20 mg/kg/day for 3-5 days, and close electrolyte monitoring with appropriate correction of abnormalities. 1

Risk Assessment and Prevention

• TLS is a potentially life-threatening complication occurring in rapidly proliferating, bulky, or highly chemo-radiosensitive cancers 1
• High-risk patients include those with:
  • Host-related factors: dehydration, hyponatremia, pre-existing renal impairment, obstructive uropathy, and hyperuricemia 1
  • Disease-related factors: bulky disease, high-grade lymphomas, acute lymphoblastic leukemia, and elevated LDH 1, 2
  • Therapy-related factors: intensive polychemotherapy including cisplatin, cytosine arabinoside, etoposide, and methotrexate 1

Treatment Algorithm

Initial Management

• Aggressive hydration should be initiated 48 hours before tumor-specific therapy when possible 1
  • Goal: maintain urine output ≥100 mL/hour in adults 1
• Rasburicase administration:
  • Dose: 0.20 mg/kg/day, infused over 30 minutes 1
  • Duration: 3-5 days 1
  • Efficacy: 96% of patients achieve uric acid levels ≤2 mg/dL within 4 hours of the first dose 3
  • Indication: initial management of plasma uric acid levels in patients receiving anticancer therapy expected to result in tumor lysis 3

Electrolyte Management

• Hyperphosphatemia:
  • Treatment: aluminum hydroxide at 50-100 mg/kg/day divided in 4 doses 1
  • Dietary phosphate restriction may also be implemented 4
• Hypocalcemia:
  • Only treat if symptomatic with calcium gluconate 50-100 mg/kg 1
  • For recurrent hypocalcemia, consider continuous intravenous calcium gluconate infusion 4
  • Caution: avoid calcium gluconate for mild hypocalcemia as it may lead to increased tissue and renal precipitation of calcium phosphate 1
• Hyperkalemia:
  • Treatment options: hydration, loop diuretics, and sodium polystyrene sulfonate 1
  • For severe cases: insulin with glucose, calcium carbonate, and sodium bicarbonate 1, 4

Monitoring Protocol

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

Indications for Dialysis

• Severe oliguria or anuria 1
• Persistent hyperkalemia 1
• Hyperphosphatemia with symptomatic hypocalcemia 1
• Hyperuricemia not responding to rasburicase 1
• Severe volume overload 1
• Acute kidney injury with worsening renal function 5
• Hemodialysis can reduce plasma uric acid levels by approximately 50% with each 6-hour treatment 1

Important Considerations and Pitfalls

• Urine alkalinization is not recommended in patients receiving rasburicase therapy 1
• Allopurinol should not be administered concurrently with rasburicase to avoid xanthine accumulation and lack of substrate for rasburicase 1
• NSAIDs should be avoided due to the risk of worsening renal function 6
• Rasburicase allows for earlier administration of chemotherapy due to rapid degradation of uric acid 1
• Monitor for hypersensitivity reactions to rasburicase, which can include allergic reactions, bronchospasm, chest pain, dyspnea, hypoxia, hypotension, shock, or urticaria 3
• Rasburicase is indicated only for a single course of treatment 3
• Early recognition and intervention are essential to prevent life-threatening complications such as cardiac arrhythmias, seizures, and sudden death 7