What are the recommendations for preventing Tumor Lysis Syndrome (TLS) in patients undergoing chemotherapy?

Tumor Lysis Syndrome Prevention

All patients at high risk for tumor lysis syndrome should receive aggressive intravenous hydration starting 48 hours before chemotherapy combined with rasburicase (0.20 mg/kg/day IV over 30 minutes for 3-5 days), not allopurinol, as the primary prophylactic agent. 1, 2

Risk Stratification

Before initiating chemotherapy, assess for the following risk factors:

Host-related factors:

• Pre-existing renal impairment 1, 3
• Dehydration or hyponatremia 1
• Obstructive uropathy 1
• Baseline hyperuricemia 1

Disease-related factors:

• Bulky disease (tumor burden) 1, 3
• High-grade lymphomas or acute lymphoblastic leukemia 1, 4
• Elevated LDH levels 1
• Rapidly proliferating malignancies 4, 5

Therapy-related factors:

• Intensive polychemotherapy regimens including cisplatin, cytarabine, etoposide, or methotrexate 1

Prevention Algorithm for High-Risk Patients

Hydration Protocol

• Initiate aggressive IV hydration 48 hours before chemotherapy when possible 6, 2
• Use central venous access for reliable fluid administration 6, 1
• Target urine output: ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 6, 1, 2
• Administer approximately 3 L/m² of fluid daily 2
• Add loop diuretics or mannitol if target urine output cannot be achieved, except in patients with obstructive uropathy or hypovolemia 6, 1, 2

Rasburicase Administration (High-Risk Patients)

Rasburicase is superior to allopurinol in high-risk patients because it converts existing uric acid to allantoin (5-10 times more soluble), providing immediate reduction of pre-existing hyperuricemia, whereas allopurinol only prevents new uric acid formation. 3

Dosing regimen:

• 0.20 mg/kg/day IV over 30 minutes 1, 2, 3, 7
• Administer first dose at least 4 hours before starting chemotherapy 2, 3
• Continue for 3-5 days 1, 2, 3
• In the FDA trial, 96% of patients achieved uric acid levels ≤2 mg/dL within 4 hours of the first dose 7

Critical contraindications:

• G6PD deficiency (causes hemolytic anemia) 2, 3
• History of anaphylaxis to rasburicase 3
• Methemoglobinemia 2, 3
• Pregnancy and lactation 3

After completing rasburicase, transition to oral allopurinol—never administer these agents concurrently to avoid xanthine accumulation and lack of substrate for rasburicase. 2, 3

Allopurinol for Low-Risk Patients Only

Low-risk patients should receive oral allopurinol (not rasburicase) combined with vigorous hydration. 3

Dosing:

• 100 mg/m² every 8 hours orally (maximum 800 mg/day) OR 200-400 mg/m²/day IV in divided doses (maximum 600 mg/day) 3
• Start 1-2 days before chemotherapy and continue for 3-7 days afterward 3
• Reduce dose by 50% or more in renal insufficiency due to drug and metabolite accumulation 3

Important limitation: Allopurinol only prevents new uric acid formation; it does not reduce pre-existing hyperuricemia and increases xanthine/hypoxanthine levels, which can cause xanthine crystal deposition in renal tubules. 3

Monitoring Protocol

For high-risk patients before TLS develops:

• Monitor every 12 hours for the first 3 days, then every 24 hours 1, 2
• Parameters: LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, calcium 1, 2

For patients with established TLS:

• Monitor every 6 hours for the first 24 hours, then daily 1, 2
• Parameters: vital signs (heart rate, blood pressure, urine output, respiratory rate), serum uric acid, electrolytes (phosphate, calcium, potassium), renal function (creatinine, BUN, urine pH, osmolality, specific gravity) 1, 2
• Place blood samples immediately on ice to prevent continued ex vivo enzymatic degradation by rasburicase, which falsely lowers measured uric acid levels 3

Management of Metabolic Abnormalities During Prevention

Hyperphosphatemia

• Mild (<1.62 mmol/L): No treatment required or aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric) 6, 1

Hypocalcemia

• Asymptomatic: No treatment required 6, 1
• Symptomatic (tetany, seizures): Calcium gluconate 50-100 mg/kg IV as single dose, cautiously repeated if necessary 6, 1
• Do not correct mild hypocalcemia as it may increase tissue and renal precipitation of calcium phosphate 1, 2

Hyperkalemia

• Mild (<6 mmol/L): Hydration, loop diuretics, sodium polystyrene 1 g/kg orally or by enema 6, 1
• Severe (≥6 mmol/L): Rapid insulin 0.1 units/kg plus 25% dextrose 2 mL/kg, calcium carbonate 100-200 mg/kg/dose, sodium bicarbonate 6, 1
• Continuous ECG monitoring is mandatory for severe hyperkalemia 6, 1

Critical Pitfalls to Avoid

• Do not use urine alkalinization in patients receiving rasburicase therapy unless other clinical conditions require it 1, 2
• Never administer allopurinol concurrently with rasburicase 2, 3
• Do not use allopurinol as primary prophylaxis in high-risk patients—in a retrospective pediatric study, 16% of patients receiving allopurinol required dialysis compared to only 2.6% receiving rasburicase 3
• Avoid loop diuretics in patients with obstructive uropathy or hypovolemia 6, 1, 2

Indications for Renal Replacement Therapy

Initiate dialysis 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