What is the management of tumor lysis syndrome?

Management of Tumor Lysis Syndrome

Initiate aggressive IV hydration 48 hours before chemotherapy targeting urine output ≥100 mL/hour in adults, and administer rasburicase 0.20 mg/kg/day (not allopurinol) as the primary prophylactic and therapeutic agent in high-risk patients. 1

Risk Stratification

Before initiating treatment, identify patients at high risk for TLS based on three categories:

Host-related factors: 1

• Dehydration
• Hyponatremia
• Pre-existing renal impairment
• Obstructive uropathy
• Baseline hyperuricemia

Disease-related factors: 1, 2

• Bulky disease or large tumor size
• High-grade lymphomas (especially Burkitt's lymphoma)
• Acute lymphoblastic leukemia (particularly B-ALL)
• Elevated LDH
• White blood cell count >50,000/mm³
• Extensive bone marrow involvement

Therapy-related factors: 1

• Intensive polychemotherapy regimens
• Cisplatin, cytosine arabinoside, etoposide, or methotrexate

Diagnostic Criteria

Use the Cairo-Bishop criteria to establish the diagnosis: 2

Laboratory TLS requires at least 2 of 4 metabolic abnormalities within 3 days before or 7 days after chemotherapy: 2

• Hyperuricemia
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia

Clinical TLS requires laboratory TLS plus at least one clinical complication: 2

• Renal failure (eGFR ≤60 mL/min)
• Cardiac arrhythmia
• Seizure

Primary Treatment Algorithm

Aggressive Hydration

Start IV hydration 48 hours before tumor-specific therapy when possible: 1

• Target urine output: ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg)
• Use central venous access for reliable fluid administration in high-risk patients 1
• Add loop diuretics (furosemide 40-80 mg IV) or mannitol if target urine output cannot be achieved, except in obstructive uropathy or hypovolemia 1, 3

Rasburicase Administration

Rasburicase is superior to allopurinol because it immediately converts existing uric acid to allantoin, providing rapid reduction of pre-existing hyperuricemia: 1, 4

• Dose: 0.20 mg/kg/day IV infused over 30 minutes 1
• Duration: 3-5 days 1
• In randomized trials, rasburicase achieved significantly lower mean uric acid area under the curve compared to allopurinol (p<0.001) 1
• Uric acid levels reach ≤2 mg/dL in 96% of patients within 4 hours of the first dose 4
• Response rate (uric acid ≤7.5 mg/dL): 87% with rasburicase vs 66% with allopurinol (p=0.0009) 4

Critical caveat: Do not administer allopurinol concurrently with rasburicase, as this causes xanthine accumulation and eliminates substrate for rasburicase 1

Critical caveat: Do not alkalinize urine in patients receiving rasburicase 1

Management of Metabolic Abnormalities

Hyperphosphatemia

Mild hyperphosphatemia (<1.62 mmol/L): 1

• No treatment required, or
• Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric)

Severe hyperphosphatemia (≥1.62 mmol/L): 3

• Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses

Hypocalcemia

Asymptomatic hypocalcemia: 1

• No treatment required

Symptomatic hypocalcemia (tetany, seizures): 1

• Calcium gluconate 50-100 mg/kg as single IV dose
• Repeat cautiously if necessary

Critical pitfall: Do not correct mild asymptomatic hypocalcemia, as calcium gluconate may lead to increased tissue and renal precipitation of calcium phosphate 1

Hyperkalemia

Mild hyperkalemia (<6 mmol/L): 3

• Aggressive IV hydration to maintain urine output ≥100 mL/hour
• Loop diuretics (furosemide 40-80 mg IV) to enhance renal potassium excretion
• Sodium polystyrene 1

Severe hyperkalemia (≥6 mmol/L or ECG changes): 1, 3

• Immediate: Calcium gluconate 10%: 50-100 mg/kg (100-200 mg/kg/dose) IV over 2-5 minutes to stabilize myocardial membrane (onset 1-3 minutes, duration 30-60 minutes; does not lower potassium) 3
• Rapid-acting: Insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg (onset 15-30 minutes, duration 4-6 hours) 1, 3
• Additional: Sodium bicarbonate 1
• Continuous ECG monitoring is mandatory 1, 3

Monitoring Protocol

High-risk patients (before TLS develops): 1

• Every 12 hours for first 3 days, then every 24 hours
• Measure: LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, calcium

Patients with established TLS: 1

• Every 6 hours for first 24 hours, then daily
• Measure: vital signs, serum uric acid, electrolytes, renal function
• Obtain immediate ECG to assess for peaked T waves, flattened P waves, prolonged PR interval, widened QRS complex 3
• Recheck potassium every 2-4 hours after initial treatment for hyperkalemia 3

Indications for Renal Replacement Therapy

Initiate hemodialysis for: 1, 3

• Severe oliguria or anuria
• Persistent hyperkalemia despite medical management
• Hyperphosphatemia with symptomatic hypocalcemia
• Hyperuricemia not responding to rasburicase
• Severe volume overload
• Refractory renal failure

Hemodialysis reduces plasma uric acid levels by approximately 50% with each 6-hour treatment and is the most effective method for removing potassium 1, 3

Special Considerations

Rasburicase allows for earlier administration of chemotherapy due to rapid degradation of uric acid 1

TLS can occur in solid tumors, though rare compared to hematologic malignancies 3

Rasburicase is indicated only for a single course of treatment 4