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

Before initiating treatment, identify high-risk patients based on three categories:

Host-related factors: 1

• Dehydration
• Pre-existing renal impairment (eGFR ≤60 mL/min)
• Obstructive uropathy
• Hyperuricemia (≥8 mg/dL)

Disease-related factors: 1, 2

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

Therapy-related factors: 1

• Intensive polychemotherapy (cisplatin, cytarabine, etoposide, methotrexate)

Immediate Diagnostic Workup

Obtain the following labs when TLS is suspected: 2

• Comprehensive metabolic panel (potassium, phosphorus, calcium, creatinine, BUN)
• Uric acid
• LDH
• Complete blood count
• ECG (mandatory to assess for hyperkalemia-induced cardiac changes) 3

Diagnostic criteria (Cairo-Bishop): Laboratory TLS requires ≥2 of 4 metabolic abnormalities (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia) within 3 days before or 7 days after chemotherapy; clinical TLS adds renal failure (eGFR ≤60 mL/min), cardiac arrhythmia, or seizure. 2

Primary Treatment Algorithm

Aggressive Hydration

• Start 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 administration 1
• Add loop diuretics (furosemide 40-80 mg IV) or mannitol if target output not achieved, except in 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, whereas allopurinol only prevents new uric acid formation. 1 In randomized trials, rasburicase achieved significantly lower uric acid levels (p<0.001) and maintained uric acid ≤2 mg/dL in 96% of patients at 4 hours. 4

• Dose: 0.20 mg/kg/day IV over 30 minutes 1
• Duration: 3-5 days 1
• Do not administer allopurinol concurrently (causes xanthine accumulation and removes rasburicase substrate) 1
• Do not alkalinize urine in patients receiving rasburicase 1
• Contraindicated in G6PD deficiency 4

Management of Electrolyte Abnormalities

Hyperkalemia:

• Mild (<6 mmol/L): Aggressive hydration + loop diuretics + sodium polystyrene 1, 3
• Severe (≥6 mmol/L or ECG changes): 1, 3
  • Calcium gluconate 10%: 50-100 mg/kg IV over 2-5 minutes (stabilizes myocardium, onset 1-3 minutes, does not lower potassium)
  • Rapid-acting insulin 0.1 units/kg IV + 25% dextrose 2 mL/kg (onset 15-30 minutes, duration 4-6 hours)
  • Sodium bicarbonate
  • Continuous ECG monitoring mandatory

Hyperphosphatemia:

• Mild (<1.62 mmol/L): No treatment required 1
• Elevated (≥1.62 mmol/L): Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric) 1, 3

Hypocalcemia:

• Asymptomatic: No treatment 1
• Symptomatic (tetany, seizures): Calcium gluconate 50-100 mg/kg as single IV dose, cautiously repeated if necessary 1
• Critical pitfall: Do not correct mild hypocalcemia—increases tissue and renal calcium phosphate precipitation 1

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

Established TLS: 1, 3

• Every 6 hours for first 24 hours, then daily
• Measure: Vital signs, serum uric acid, electrolytes, renal function
• Continuous ECG monitoring for hyperkalemia

Indications for Hemodialysis

Initiate renal replacement therapy for: 1, 3

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

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

Critical Pitfalls to Avoid

• Never use allopurinol instead of rasburicase in high-risk patients—allopurinol cannot reduce pre-existing hyperuricemia 1
• Never alkalinize urine with rasburicase therapy—no benefit and may worsen hyperphosphatemia 1
• Never treat asymptomatic hypocalcemia—worsens calcium phosphate precipitation 1
• Never delay dialysis in refractory cases—it is the most effective method for removing potassium and correcting metabolic abnormalities 3
• Never administer rasburicase and allopurinol together 1