What are the diagnostic criteria and treatment options for tumor lysis syndrome?

Diagnosis of Tumor Lysis Syndrome

Tumor lysis syndrome is diagnosed using the Cairo-Bishop criteria, which define laboratory TLS as at least 2 of 4 metabolic abnormalities (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia) occurring within 3 days before or 7 days after chemotherapy initiation, while clinical TLS requires laboratory TLS plus at least one clinical complication (renal failure with eGFR ≤60 mL/min, cardiac arrhythmia, or seizure). 1

Diagnostic Criteria

Laboratory TLS

Laboratory TLS requires at least 2 of the following 4 biochemical abnormalities occurring within the specified timeframe: 1

• Hyperuricemia (elevated uric acid)
• Hyperkalemia (elevated potassium)
• Hyperphosphatemia (elevated phosphate)
• Hypocalcemia (decreased calcium)

These metabolic derangements result from rapid tumor cell lysis releasing intracellular contents into the bloodstream. 2, 3

Clinical TLS

Clinical TLS is diagnosed when laboratory TLS is present plus at least one of the following clinical complications: 1

• Acute kidney injury with eGFR ≤60 mL/min/1.73 m²
• Cardiac arrhythmia (typically from hyperkalemia)
• Seizure (from hypocalcemia or metabolic derangements)

The Cairo-Bishop criteria specifically define the temporal relationship: these abnormalities must occur within 3 days before or 7 days after initiating chemotherapy. 1

Essential Diagnostic Workup

When TLS is suspected, immediately obtain: 1

• Comprehensive metabolic panel (includes electrolytes, calcium, phosphate, creatinine)
• Lactate dehydrogenase (LDH) level
• Complete blood count
• Calculate eGFR using the MDRD formula: eGFR (mL/min/1.73 m²) = 175 × (serum creatinine in mmol/L × 0.0113)^-1.154 × age^-0.203 × (0.742 if female) 1

Risk Stratification

Highest risk malignancies include: 1

• Burkitt's lymphoma (highest risk)
• B-cell acute lymphoblastic leukemia (B-ALL)
• Other rapidly proliferating hematologic malignancies

Clinical risk factors that predict TLS development: 1

• Elevated serum LDH level
• White blood cell count >50,000/mm³
• Extensive bone marrow involvement
• Large tumor size or bulky disease
• Elevated pre-treatment serum uric acid level
• Pre-existing renal damage
• Tumor infiltration in the kidney
• Obstructive uropathy
• Advanced age

Treatment of Tumor Lysis Syndrome

Immediate Management for Clinical TLS

All patients with clinical TLS require aggressive intravenous hydration through central venous access plus rasburicase immediately to prevent life-threatening complications including acute renal failure, cardiac arrhythmias, seizures, and death. 4

Hydration protocol: 4

• Start IV hydration at least 48 hours before chemotherapy when possible (though rasburicase allows earlier chemotherapy if needed)
• Maintain urine output at minimum 100 mL/hour (or 3 mL/kg/hour in children <10 kg)
• Use loop diuretics (furosemide) or mannitol to achieve target urine output if needed, except in patients with obstructive uropathy or hypovolemia 4

Rasburicase administration: 5

• Dose: 0.2 mg/kg IV over 30 minutes once daily
• Continue for 3-5 days as needed
• Give first dose at least 4 hours before chemotherapy when possible 4
• Do not give allopurinol concurrently with rasburicase, as this causes xanthine accumulation and removes substrate for rasburicase 4

Management of Specific Electrolyte Abnormalities

Hyperkalemia management (stratified by severity): 4

Mild hyperkalemia (<6 mmol/L):

• Aggressive IV hydration plus loop diuretics (furosemide 40-80 mg IV)
• Sodium polystyrene 1 g/kg orally or by enema 6

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

• Calcium gluconate 50-100 mg/kg IV over 2-5 minutes to stabilize myocardial membrane 4
• Rapid insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg IV (onset 15-30 minutes, duration 4-6 hours) 4
• Sodium bicarbonate to correct acidosis 6
• Continuous ECG monitoring is mandatory 6

Hyperphosphatemia management: 6

• Mild hyperphosphatemia (<1.62 mmol/L) does not require treatment or can be treated with aluminum hydroxide 50-100 mg/kg/day divided in 4 doses orally or by nasogastric tube

Hypocalcemia management: 6

• Asymptomatic hypocalcemia does not require treatment
• For symptomatic hypocalcemia (tetany, seizures): calcium gluconate 50-100 mg/kg IV infused cautiously and repeated if necessary

Treatment for Laboratory TLS

The same aggressive treatment as clinical TLS is recommended for: 4

• All adults with laboratory TLS
• Children at high risk for TLS
• Children with rapid worsening of biochemical parameters

This means hydration plus rasburicase should be administered even before clinical complications develop in these populations. 6

Indications for Urgent Hemodialysis

Initiate hemodialysis urgently when: 4

• Oliguria or anuria develops despite aggressive hydration
• Severe, refractory hyperkalemia (≥6 mmol/L unresponsive to medical management)
• Symptomatic hypocalcemia refractory to treatment
• Severe hyperphosphatemia with calcium-phosphate precipitation

Hemodialysis effectively removes uric acid (clearance 70-100 mL/min) and phosphate, with plasma uric acid falling approximately 50% with each 6-hour treatment. 6 Oliguria from acute uric acid nephropathy typically responds rapidly to hemodialysis, often restarting diuresis as plasma uric acid falls to 10 mg/dL. 6

Laboratory Monitoring

Monitoring frequency: 4

• Recheck potassium every 2-4 hours after initial treatment
• Monitor uric acid, electrolytes, phosphate, calcium every 6 hours for the first 24 hours
• Measure hourly urine output
• Continuous ECG monitoring to detect hyperkalemia-induced arrhythmias

Critical Pitfalls to Avoid

Do not use loop diuretics in patients with anuria or established oliguria despite adequate hydration—these patients require urgent hemodialysis instead. 4

Do not treat asymptomatic hypocalcemia, as calcium administration in the setting of hyperphosphatemia can precipitate calcium-phosphate crystals in tissues and worsen renal injury. 6

Do not combine allopurinol with rasburicase, as this interferes with rasburicase activity and causes xanthine accumulation. 4

Recognize spontaneous TLS can occur in solid tumors (though rare), particularly in rapidly growing metastatic disease, even before chemotherapy initiation. 2, 7 Early recognition is critical as delayed treatment significantly increases mortality.