What is the management of tumor lysis syndrome?

Management of Tumor Lysis Syndrome

Initiate aggressive IV hydration 48 hours before chemotherapy with rasburicase 0.20 mg/kg/day as the primary prophylactic agent in high-risk patients, targeting urine output ≥100 mL/hour in adults. 1

Risk Stratification

Identify high-risk patients before initiating cancer therapy by assessing three categories of risk factors:

Host-related factors: 1

• Dehydration
• Hyponatremia
• Pre-existing renal impairment (eGFR ≤60 mL/min) 2
• Obstructive uropathy
• Baseline hyperuricemia (>7.5 mg/dL) 2

Disease-related factors: 1, 2

• Bulky disease or large tumor size
• High-grade lymphomas (especially Burkitt's lymphoma)
• Acute lymphoblastic leukemia (B-ALL)
• Elevated LDH
• White blood cell count >50,000/mm³ 2
• Extensive bone marrow involvement 2

Therapy-related factors: 1

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

Diagnostic Criteria

Use the Cairo-Bishop criteria to diagnose TLS: 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 Prevention and Treatment Algorithm

Hydration Protocol

Start aggressive 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) 1
• 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 1, 3
• Critical caveat: Do not use diuretics in patients with obstructive uropathy or hypovolemia 1, 3

Rasburicase Administration

Rasburicase is superior to allopurinol in high-risk patients 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
• Efficacy: In adults, 96% of patients achieved uric acid levels ≤2 mg/dL within 4 hours of the first dose 4
• Response rate: 87% of patients maintained uric acid ≤7.5 mg/dL from day 3 to day 7 4

Critical contraindication: Never administer allopurinol concurrently with rasburicase, as this causes xanthine accumulation and eliminates substrate for rasburicase 1

Do not use urine alkalinization in patients receiving rasburicase therapy 1

Management of Electrolyte Abnormalities

Hyperkalemia

Mild hyperkalemia (<6 mmol/L): 3

• Continue aggressive IV hydration
• Add loop diuretics (furosemide 40-80 mg IV) to enhance renal potassium excretion 3
• Sodium polystyrene sulfonate 1

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

• Immediate: Calcium gluconate 10%: 50-100 mg/kg IV over 2-5 minutes to stabilize myocardial membrane (onset 1-3 minutes, duration 30-60 minutes) 3
• Shift potassium intracellularly: Rapid insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg (onset 15-30 minutes, duration 4-6 hours) 1, 3
• Additional measures: Calcium carbonate 100-200 mg/kg/dose and sodium bicarbonate 1
• Mandatory: Continuous ECG monitoring 1, 3

Hyperphosphatemia

Mild hyperphosphatemia (<1.62 mmol/L): No treatment required 1

Moderate to severe hyperphosphatemia (≥1.62 mmol/L): 1, 3

• Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric)

Hypocalcemia

Asymptomatic hypocalcemia: No treatment required 1

Critical principle: Do not correct mild hypocalcemia with calcium gluconate, as this increases tissue and renal precipitation of calcium phosphate 1

Symptomatic hypocalcemia (tetany, seizures): 1

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

Monitoring Protocol

High-risk patients (before TLS develops): 1

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

Patients with established TLS: 1

• Monitor every 6 hours for first 24 hours, then daily
• Measurements: vital signs, serum uric acid, complete electrolyte panel, renal function
• Continuous ECG monitoring for hyperkalemia 3

After initial hyperkalemia treatment: 3

• Recheck potassium every 2-4 hours

Indications for Renal Replacement Therapy

Initiate hemodialysis for: 1

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

Efficacy: Hemodialysis reduces plasma uric acid levels by approximately 50% with each 6-hour treatment 1

Critical Pitfalls to Avoid

• Never delay rasburicase in high-risk patients – it allows for earlier administration of chemotherapy due to rapid uric acid degradation 1
• Never alkalinize urine with rasburicase – this is unnecessary and potentially harmful 1
• Never treat asymptomatic hypocalcemia – calcium administration risks calcium phosphate precipitation 1
• Never combine allopurinol with rasburicase – this eliminates rasburicase efficacy 1
• Never use diuretics in obstructive uropathy – this worsens renal injury 1, 3