Tumor Lysis Syndrome Diagnosis and Management
Diagnostic Criteria
Tumor lysis syndrome is diagnosed based on laboratory abnormalities (laboratory TLS) or laboratory findings plus clinical complications (clinical TLS), requiring immediate recognition to prevent life-threatening complications. 1
Laboratory TLS (LTLS)
- Requires two or more of the following abnormal serum values within 3 days before or 7 days after initiating anticancer therapy: 1
Clinical TLS (CTLS)
- Requires laboratory TLS plus one or more of the following clinical complications: 1
Risk Stratification
Risk assessment must be performed before initiating chemotherapy to determine appropriate prophylactic measures, as high-risk patients have significantly higher mortality rates (83% vs 24% in those without TLS). 1
High-Risk Factors
Host-related factors: 2
- Pre-existing renal impairment (including renal infiltration by malignancy)
- Dehydration
- Obstructive uropathy
- Hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults)
- Hyponatremia (limited to solid tumors)
Disease-related factors: 2
- Burkitt's lymphoma and B-cell ALL (highest risk, 26.4% TLS rate) 1
- High-grade lymphomas, particularly T-cell lymphoblastic NHL 2
- Acute lymphoblastic leukemia in adults and advanced T-cell ALL in children 2
- AML with WBC >100 × 10⁹/L 1
- Bulky disease (especially bulky SCLC or massive liver metastases) 2
- Metastatic germ cell tumors (gonadal or extragonadal) 2
- Elevated serum LDH >2 times upper normal limit 2
Therapy-related factors: 2
- Intensive polychemotherapy including cisplatin, cytosine arabinoside, etoposide, methotrexate
Pre-Treatment Evaluation
Before starting any anticancer therapy in at-risk patients, the following evaluations are mandatory: 2
- Creatinine clearance or estimated GFR 2
- Serum LDH levels 2
- Renal ultrasound in all patients undergoing chemotherapy 2
- Baseline uric acid, potassium, phosphate, and calcium 2
Prophylaxis Strategy
Low-Risk Patients
Low-risk patients should receive oral allopurinol 100 mg/m² three times daily (maximum 800 mg/day), vigorous hydration (≥2 L/m²/day), and urine alkalinization. 2, 4
- Hydration should start at least 48 hours before tumor-specific therapy when possible 2
- Target urine output: ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 2, 5
- Loop diuretics may be required to maintain urine output, except in obstructive uropathy or hypovolemia 2, 5
High-Risk Patients
High-risk patients should receive rasburicase 0.20 mg/kg/day IV over 30 minutes plus aggressive hydration in an inpatient setting, NOT allopurinol. 2, 4, 6
Critical dosing and timing: 2, 4
- Administer first dose at least 4 hours before starting tumor-specific therapy
- Continue for 3-5 days
- After completing rasburicase, transition to oral allopurinol
- Never administer allopurinol and rasburicase concurrently to avoid xanthine accumulation and lack of substrate for rasburicase 2, 4
Rasburicase contraindications: 2, 4, 6
- G6PD deficiency (causes hemolytic anemia)
- Methemoglobinemia
- History of anaphylaxis to rasburicase
- Pregnancy and lactation
Evidence supporting rasburicase superiority: In a retrospective pediatric study comparing urate oxidase (rasburicase) versus allopurinol, only 2.6% of rasburicase-treated patients required dialysis compared to 16% receiving allopurinol. 2, 4
Monitoring Protocol
High-Risk Patients (Before TLS Develops)
Monitor every 12 hours for the first 3 days, then every 24 hours: 2, 1
- LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, calcium
Patients with Established TLS
Monitor every 6 hours for the first 24 hours, then daily: 2
- Vital signs (heart rate, blood pressure, urine output, respiratory rate)
- Uric acid, electrolytes (potassium, phosphate, calcium), creatinine, BUN
- Continuous ECG monitoring for hyperkalemic patients 2
Critical sample handling: Blood samples must be placed immediately on ice to prevent continued ex vivo enzymatic degradation by rasburicase, which falsely lowers measured uric acid levels. 4, 6
Treatment of Established TLS
All patients with clinical TLS or laboratory TLS with worsening parameters should receive hydration through central venous access and rasburicase immediately. 2, 5
Hydration Management
- Aggressive IV hydration: 3 L/m²/day to maintain urine output ≥100 mL/hour in adults 2, 5
- Loop diuretics (not thiazides) may be required except in obstructive uropathy or hypovolemia 2, 5
- Measure urine osmolality and fractional excretion of sodium to assess hydration status 2
Rasburicase Administration
- Dose: 0.20 mg/kg/day IV over 30 minutes for 3-5 days 2, 5, 6
- In Study 4,87% of rasburicase-treated patients achieved uric acid response (≤7.5 mg/dL) compared to 66% with allopurinol alone 6
- Uric acid levels reached ≤2 mg/dL in 96% of patients within 4 hours of first dose 6
Electrolyte Management
Hyperphosphatemia: 2
- Mild (<1.62 mmol/L): aluminum hydroxide 50-100 mg/kg/day divided in 4 doses orally or by nasogastric tube
Hypocalcemia: 2
- Asymptomatic: no treatment required
- Symptomatic (tetany, seizures): calcium gluconate 50-100 mg/kg IV, cautiously repeated if necessary
Hyperkalemia: 2
- Mild (<6 mmol/L) asymptomatic: hydration, loop diuretics, sodium polystyrene 1 g/kg orally or by enema
- Severe: rapid insulin 0.1 units/kg plus 25% dextrose 2 mL/kg; calcium carbonate 100-200 mg/kg/dose; sodium bicarbonate to stabilize myocardial membrane and correct acidosis
- Continuous ECG monitoring mandatory
Urine Alkalinization
Do NOT alkalinize urine in patients receiving rasburicase therapy unless other clinical conditions specifically require it. 2
Indications for Dialysis
Renal replacement therapy should be initiated for: 2, 1
- Severe oliguria or anuria unresponsive to medical management
- Persistent hyperkalemia despite medical therapy
- Hyperphosphatemia with symptomatic hypocalcemia
- Hyperuricemia not responding to rasburicase
- Severe volume overload
- Symptomatic uremia
Hemodialysis effectively removes uric acid (clearance 70-100 mL/min) and phosphate, with plasma uric acid falling approximately 50% with each 6-hour treatment. 2
Common Pitfalls to Avoid
- Never give allopurinol and rasburicase concurrently – causes xanthine accumulation and removes rasburicase substrate 2, 4
- Always place blood samples on ice immediately when rasburicase has been administered to prevent falsely low uric acid readings 4, 6
- Reduce allopurinol dose by 50% in renal impairment due to drug and metabolite accumulation 2, 4
- Screen for G6PD deficiency before rasburicase to prevent life-threatening hemolysis 2, 6
- Do not delay chemotherapy without addressing TLS risk first – mortality is 83% for clinical TLS in AML versus 24% without TLS 1
- Avoid urine alkalinization with rasburicase – not indicated and may complicate management 2
- Do not use thiazide diuretics – use loop diuretics only 5