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) management, with renal replacement therapy indicated for severe cases not responding to conservative measures. 1

Risk Assessment and Prevention

• TLS is a potentially life-threatening complication occurring in patients with rapidly proliferating, bulky, or highly chemo-radiosensitive cancers, particularly high-grade lymphomas and acute lymphoblastic leukemia 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 tumor burden, elevated LDH 1
  • Therapy-related factors: 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 reduces plasma uric acid levels, with 96% of patients achieving levels ≤2 mg/dL within 4 hours of the first dose 2
• Do not administer allopurinol concurrently with rasburicase to avoid xanthine accumulation 1
• Rasburicase is indicated for the initial management of plasma uric acid levels in patients receiving anticancer therapy expected to result in tumor lysis 2

3. Electrolyte Management

• Hyperphosphatemia: Administer 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: Treat with hydration, loop diuretics, and sodium polystyrene sulfonate; severe cases may require insulin and glucose, calcium carbonate, and sodium bicarbonate 1

Monitoring

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

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, 3

Important Considerations and Pitfalls

• Do not alkalinize urine in patients receiving rasburicase therapy 1
• Avoid calcium gluconate for mild hypocalcemia as it may lead to increased tissue and renal precipitation of calcium phosphate 1
• Avoid NSAIDs due to the risk of worsening renal function in patients already at risk for acute kidney injury 4
• Monitor for drug interactions with CYP3A4 inhibitors if pain management is needed, as they may increase fentanyl plasma concentrations 4
• Rasburicase contraindications: Patients with G6PD deficiency are at risk for hemolysis and methemoglobinemia when receiving rasburicase 2
• Coordinate timing of medications with dialysis sessions if the patient requires renal replacement therapy 4

Clinical Manifestations Requiring Urgent Intervention

• Acute kidney injury with rising creatinine 5
• Cardiac arrhythmias due to hyperkalemia 5
• Seizures or altered mental status from electrolyte abnormalities 5
• Respiratory failure 5

By following this comprehensive management approach, clinicians can effectively prevent and treat tumor lysis syndrome, reducing the associated morbidity and mortality in high-risk patients.