What are the diagnostic and management strategies for tumor lysis syndrome?

Diagnosis and 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), while hydration and rasburicase should also be administered to adults with laboratory TLS, children with high risk of TLS, or children with rapidly worsening biochemical parameters of TLS. 1

Diagnosis of TLS

TLS is diagnosed based on laboratory and clinical criteria:

Laboratory TLS

Requires at least 2 of the following biochemical abnormalities:

• Hyperuricemia (>8 mg/dL or 25% increase from baseline)
• Hyperkalemia (>6 mmol/L or 25% increase from baseline)
• Hyperphosphatemia (>4.5 mg/dL or 25% increase from baseline)
• Hypocalcemia (<7 mg/dL or 25% decrease from baseline)

Clinical TLS

Defined as laboratory TLS plus one or more of the following:

• Acute kidney injury
• Cardiac arrhythmias
• Seizures
• Death

Risk Stratification

High-risk patients:

• Hematologic malignancies with high proliferation rates (Burkitt's lymphoma, ALL)
• Bulky disease
• High sensitivity to cytotoxic therapy
• Pre-existing renal dysfunction
• Elevated baseline uric acid

Low-risk patients:

• Solid tumors with low proliferation rates
• Low tumor burden
• Normal renal function
• Normal baseline uric acid

Management Algorithm

1. Prophylaxis for High-Risk Patients:

• Hydration through central venous access
• Rasburicase 0.20 mg/kg/day IV infused over 30 minutes 1
• Begin at least 4 hours before starting tumor-specific therapy
• Continue for 3-5 days
• Maintain urine output at 100 mL/hour in adults (3 mL/kg/hour in children <10 kg)

2. Prophylaxis for Low-Risk Patients:

• Hydration
• Oral allopurinol 100 mg/m² three times daily (maximum 800 mg/day) 1, 2

3. Treatment of Established TLS:

For Hyperuricemia:

• Rasburicase 0.20 mg/kg/day IV 1
• Contraindicated in G6PD deficiency, metahemoglobinemia, or other metabolic disorders that can cause hemolytic anemia

For Hyperphosphatemia:

• Mild (<1.62 mmol/L): No treatment or aluminum hydroxide 50-100 mg/kg/day in 4 divided doses 1
• Severe: Phosphate binders and dietary phosphate restriction 3

For Hypocalcemia:

• Asymptomatic: No treatment
• Symptomatic (tetany, seizures): Calcium gluconate 50-100 mg/kg IV 1

For Hyperkalemia:

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

4. Indications for Hemodialysis:

• Severe oliguria or anuria
• Persistent hyperkalemia
• Severe hyperphosphatemia
• Symptomatic hypocalcemia
• Volume overload unresponsive to diuretics
• Uremic symptoms 1

Important Considerations

• Urine alkalinization is no longer recommended 1
• Do not administer allopurinol concurrently with rasburicase to avoid xanthine accumulation 1
• Monitor electrolytes, renal function, and uric acid levels every 4-6 hours in high-risk patients
• Hemodialysis can reduce uric acid levels by approximately 50% with each 6-hour treatment 1

Common Pitfalls to Avoid

1. Delaying prophylaxis in high-risk patients
2. Inadequate hydration
3. Simultaneous use of allopurinol and rasburicase
4. Failing to monitor for G6PD deficiency before rasburicase administration
5. Treating asymptomatic hypocalcemia (can worsen calcium phosphate precipitation)
6. Administering calcium in hyperphosphatemic patients without addressing the hyperphosphatemia first
7. Overlooking the need for cardiac monitoring in hyperkalemic patients

Early recognition of patients at risk and prompt initiation of appropriate prophylaxis and treatment are essential to prevent the life-threatening complications of TLS, including acute kidney injury, cardiac arrhythmias, seizures, and death.