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 (not allopurinol) in high-risk patients, targeting urine output ≥100 mL/hour in adults. 1

Risk Stratification

Identify high-risk patients before initiating cancer therapy:

Disease factors:

• Burkitt's lymphoma and B-cell acute lymphoblastic leukemia carry the highest risk 2
• High-grade lymphomas, bulky disease, and elevated LDH 1
• White blood cell count >50,000/mm³ or extensive bone marrow involvement 2

Host factors:

• Pre-existing renal impairment, obstructive uropathy, or dehydration 1
• Elevated baseline uric acid (≥8 mg/dL) or hyperuricemia 1, 2
• Advanced age 2

Therapy factors:

• Intensive polychemotherapy including cisplatin, cytosine arabinoside, etoposide, and methotrexate 1

Diagnostic Criteria

Use the Cairo-Bishop criteria to diagnose TLS:

Laboratory TLS requires ≥2 of these metabolic abnormalities within 3 days before or 7 days after chemotherapy:

• Hyperuricemia
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia 2

Clinical TLS requires laboratory TLS plus ≥1 clinical complication:

• Renal failure (eGFR ≤60 mL/min)
• Cardiac arrhythmia
• Seizure 2

Obtain comprehensive metabolic panel, LDH, complete blood count, and ECG immediately when TLS is suspected 2, 3

Prevention Protocol for High-Risk Patients

Hydration:

• Start aggressive IV hydration 48 hours before chemotherapy 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 1
• Add loop diuretics (furosemide 40-80 mg IV) or mannitol if target urine output not achieved, except in obstructive uropathy or hypovolemia 1, 4

Rasburicase (preferred over allopurinol):

• Administer 0.20 mg/kg/day IV over 30 minutes for 3-5 days 1
• Rasburicase converts existing uric acid to allantoin, providing immediate reduction of hyperuricemia 1
• In randomized trials, rasburicase achieved significantly lower uric acid levels compared to allopurinol (p<0.001) 1
• Rasburicase reduced uric acid to ≤2 mg/dL in 96% of patients within 4 hours 5
• Do not administer allopurinol concurrently with rasburicase to avoid xanthine accumulation and lack of substrate 1

Avoid urine alkalinization in patients receiving rasburicase 1

Treatment of Established TLS

Hyperkalemia Management

Mild hyperkalemia (<6 mmol/L):

• Continue aggressive IV hydration 4
• Add loop diuretics (furosemide 40-80 mg IV) to enhance renal potassium excretion 4
• Use sodium polystyrene 1

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

• Administer calcium gluconate 10%: 50-100 mg/kg IV over 2-5 minutes to stabilize myocardial membrane (onset 1-3 minutes, duration 30-60 minutes) 1, 4
• Give rapid-acting insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg (onset 15-30 minutes, duration 4-6 hours) 1, 4
• Add calcium carbonate 100-200 mg/kg/dose and sodium bicarbonate 1
• Continuous ECG monitoring is mandatory 1, 4
• Recheck potassium every 2-4 hours after initial treatment 4

Hyperphosphatemia Management

Mild hyperphosphatemia (<1.62 mmol/L):

• No treatment required 1

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

• Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric) 1, 4

Hypocalcemia Management

Asymptomatic hypocalcemia:

• No treatment required 1
• Do not correct mild hypocalcemia with calcium gluconate as it may increase tissue and renal precipitation of calcium phosphate 1

Symptomatic hypocalcemia (tetany, seizures):

• Calcium gluconate 50-100 mg/kg as single IV dose, cautiously repeated if necessary 1

Hyperuricemia Management

If hyperuricemia persists despite prophylaxis:

• Add or continue rasburicase at same dosing schedule 4
• Rasburicase allows for earlier administration of chemotherapy due to rapid uric acid degradation 1

Monitoring Protocol

High-risk patients (before TLS develops):

• Monitor every 12 hours for first 3 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 first 24 hours, then daily 1
• Measure vital signs, serum uric acid, electrolytes, and renal function 1
• Continuous ECG monitoring for hyperkalemia 1, 4

Indications for Renal Replacement Therapy

Initiate hemodialysis for:

• Severe oliguria or anuria 1
• Persistent hyperkalemia despite medical management 1
• Hyperphosphatemia with symptomatic hypocalcemia 1
• Hyperuricemia not responding to rasburicase 1
• Severe volume overload 1
• Hemodialysis reduces plasma uric acid by approximately 50% with each 6-hour treatment 1

Critical Pitfalls to Avoid

• Never alkalinize urine in patients receiving rasburicase as it is unnecessary and may worsen hyperphosphatemia 1
• Never give allopurinol with rasburicase concurrently 1
• Never correct asymptomatic hypocalcemia as calcium administration increases calcium-phosphate precipitation 1
• Never delay rasburicase in high-risk patients - it is superior to allopurinol for immediate uric acid reduction 1, 5
• Rasburicase is indicated only for a single course of treatment 5