What measures can be taken to prevent tumor lysis syndrome in high-risk patients with bulky disease or high white blood cell counts?

Prevention of Tumor Lysis Syndrome

Tumor lysis syndrome is prevented through risk-stratified prophylaxis: high-risk patients (bulky disease, high WBC, elevated LDH) require aggressive IV hydration plus rasburicase 0.20 mg/kg/day, while low-risk patients receive hydration plus oral allopurinol. 1, 2

Risk Stratification

Before initiating prophylaxis, identify high-risk features that mandate intensive prevention:

Disease-related factors:

• Bulky disease (especially bulky SCLC or massive liver metastases) 1
• High-grade lymphomas (Burkitt's lymphoma, T-cell lymphoblastic NHL) 1
• Acute lymphoblastic leukemia in adults or advanced T-cell ALL in children 1
• Elevated LDH >2 times upper normal limit 1
• High white blood cell counts 2

Host-related factors:

• Pre-existing renal impairment 1
• Hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults) 1
• Dehydration or obstructive uropathy 1

Therapy-related factors:

• Intensive polychemotherapy (cisplatin, cytarabine, etoposide, methotrexate) 1

Prevention Protocol for High-Risk Patients

Rasburicase is the cornerstone for high-risk prophylaxis:

• Administer 0.20 mg/kg/day IV over 30 minutes 1, 3
• Give first dose at least 4 hours before starting chemotherapy 1
• Continue for 3-5 days 1
• Rasburicase converts existing uric acid to allantoin, which is 5-10 times more soluble than uric acid 1, 2
• After completing rasburicase, transition to oral allopurinol 1

Critical: Do NOT give allopurinol concurrently with rasburicase - this causes xanthine accumulation and eliminates substrate for rasburicase activity 1, 2

Aggressive hydration protocol:

• Start IV hydration 48 hours before chemotherapy when possible 1
• Administer at least 2-3 L/m²/day 1, 4
• Target urine output ≥100 mL/hour in adults or 3 mL/kg/hour in children <10 kg 1, 4
• Loop diuretics may be needed to maintain urine output, but only after confirming adequate hydration and ruling out obstructive uropathy or hypovolemia 1, 4

Prevention Protocol for Low-Risk Patients

Low-risk patients require less intensive prophylaxis:

• Oral allopurinol 100 mg/m² three times daily (maximum 800 mg/day) 1, 4
• Vigorous hydration (≥2 L/m²/day) 1
• Urine alkalinization may be considered in low-risk patients 1

Allopurinol blocks xanthine oxidase, preventing conversion of hypoxanthine and xanthine to uric acid, but does not reduce existing elevated uric acid levels 1, 2

Critical Pitfalls to Avoid

Do NOT alkalinize urine in patients receiving rasburicase - this increases calcium-phosphate precipitation risk and reduces xanthine solubility 1, 2, 4

Rasburicase is absolutely contraindicated in:

• G6PD deficiency (causes severe hemolytic anemia) 1, 3
• Methemoglobinemia 3
• Pregnancy 3

These patients must receive allopurinol, hydration, and urine alkalinization instead 1

Special sample handling required: Rasburicase causes enzymatic degradation of uric acid in blood samples at room temperature, leading to falsely low readings - samples must be immediately placed on ice and analyzed within 4 hours 3

Pre-Treatment Evaluation

Obtain baseline assessments before starting prophylaxis:

• Creatinine clearance or estimated GFR 1
• Serum LDH 1
• Renal ultrasound in all patients undergoing chemotherapy 1
• Baseline electrolytes (uric acid, potassium, phosphorus, calcium, BUN) 5

Monitoring During Prophylaxis

For high-risk patients receiving prophylaxis:

• Monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours for first 3 days, then every 24 hours 1, 5

For established TLS:

• Monitor vital signs and all laboratory parameters every 6 hours for first 24 hours, then daily 1, 5

Evidence Supporting Rasburicase Superiority

A retrospective analysis comparing French children (who received urate oxidase) versus UK children (who received allopurinol) for B-cell non-Hodgkin's lymphoma demonstrated that only 2.6% of French patients required dialysis compared to 16% of UK patients 1. In adult studies, 87% of patients receiving rasburicase achieved uric acid control versus 66% with allopurinol alone, with 96% of rasburicase-treated patients achieving uric acid ≤2 mg/dL within 4 hours 3

Nephrology Consultation

Obtain nephrology consultation before starting therapy in patients with:

• Previous episodes of clinical TLS 1
• Significant pre-existing renal impairment 6
• High-risk features requiring potential dialysis access 6

Patients with successful tumor debulking and no end-organ dysfunction from previous TLS do not require prophylaxis once the offending condition has resolved 1