What is the management of tumor lysis syndrome?

Management of Tumor Lysis Syndrome

Aggressive hydration, rasburicase administration, and electrolyte management are the cornerstones of tumor lysis syndrome (TLS) treatment, with renal replacement therapy indicated for severe cases not responding to medical management. 1

Risk Assessment

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

Treatment Algorithm

1. Hydration

• Begin aggressive hydration 48 hours before tumor-specific therapy when possible 1
• Target urine output ≥100 mL/hour in adults 1

2. Hyperuricemia Management

• Administer rasburicase at 0.20 mg/kg/day, infused over 30 minutes, for 3-5 days 1, 2
• Rasburicase rapidly decreases plasma uric acid levels by 86% within 4 hours of the first dose (compared to only 12% with allopurinol) 2, 3
• Chemotherapy can typically be started 4 hours after initiation of rasburicase treatment 2
• Important: Do not administer allopurinol concurrently with rasburicase to avoid xanthine accumulation 1, 2

3. Electrolyte Management

• Hyperphosphatemia: Administer aluminum hydroxide at 50-100 mg/kg/day divided in 4 doses 1
• Hypocalcemia: Treat only if symptomatic with calcium gluconate 50-100 mg/kg 1
• Hyperkalemia: Manage with hydration, loop diuretics, and sodium polystyrene; severe cases require insulin with glucose, calcium carbonate, and sodium bicarbonate 1, 4

4. Monitoring

• High-risk patients: Monitor every 12 hours for first three days, then every 24 hours 1
• Parameters to measure: LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium 1
• Patients with established TLS: Monitor every 6 hours for first 24 hours, then daily 1

5. Indications for Renal Replacement Therapy

• Severe oliguria or anuria 1
• Persistent hyperkalemia 1
• Hyperphosphatemia with symptomatic hypocalcemia 1
• Hyperuricemia not responding to rasburicase 1
• Severe volume overload 1
• Hemodialysis can reduce plasma uric acid levels by approximately 50% with each 6-hour treatment 1, 4

Important Considerations and Pitfalls

• Urine alkalinization is not recommended in patients receiving rasburicase therapy 1, 2
• Do not use calcium gluconate to correct mild hypocalcemia as it may lead to increased tissue and renal precipitation of calcium phosphate 1
• Screen for G6PD deficiency before administering rasburicase to avoid hemolysis 2
• Rasburicase is indicated only for a single course of treatment due to risk of hypersensitivity reactions 3
• Rasburicase degrades existing uric acid, while allopurinol only prevents new formation by inhibiting xanthine oxidase - this explains rasburicase's superior efficacy in acute management 2
• In ESRD patients with TLS, daily hemodialysis may be required rather than relying on hydration alone 5

FDA-Approved Indication

• Rasburicase (Elitek) is FDA-approved for the initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis 3
• Clinical trials show that 96% of patients treated with rasburicase achieved uric acid levels ≤2 mg/dL within 4 hours of the first dose 3