Tumor Lysis Syndrome Prophylaxis Regimen
High-risk patients should receive rasburicase (0.20 mg/kg/day IV) plus aggressive hydration as first-line prophylaxis, while low-risk patients should receive oral allopurinol, hydration, and urine alkalinization. 1, 2
Risk Stratification for TLS Prophylaxis
High-Risk Factors:
Host-related factors:
- Dehydration
- Hyponatremia (in solid tumors)
- Pre-existing renal impairment
- Obstructive uropathy
- Hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults)
Disease-related factors:
- Bulky disease (especially SCLC or massive liver metastases)
- Metastatic germ cell tumors
- High-grade lymphomas (particularly Burkitt's and T-cell lymphoblastic NHL)
- Acute lymphoblastic leukemia in adults and advanced T-cell ALL in children
- Elevated serum LDH (>2× upper normal limit)
Therapy-related factors:
- Intensive polychemotherapy including cisplatin, cytosine arabinoside, etoposide, methotrexate
Prophylaxis Protocol Based on Risk
High-Risk Patients:
- Rasburicase: 0.20 mg/kg/day IV, infused over 30 minutes
- Start at least 4 hours before chemotherapy
- Continue for 3-5 days
- Do NOT administer allopurinol concurrently with rasburicase
- Hydration: Maintain urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg)
- Setting: Inpatient management required
Low-Risk Patients:
- Allopurinol: 100 mg/m² three times daily (maximum 800 mg/day) orally
- Hydration: ≥2 L/m²/day
- Urine alkalinization: Consider for patients not receiving rasburicase
Special Considerations:
- Patients with G6PD deficiency, metahemoglobinemia, or other metabolic disorders that can cause hemolytic anemia should NOT receive rasburicase
- These patients should receive allopurinol, hydration, and urine alkalinization instead 1, 2
Timing and Duration
- Start prophylaxis at least 48 hours before tumor-specific therapy when possible
- After completing rasburicase course, transition to oral allopurinol
- Continue prophylaxis throughout chemotherapy until uric acid levels normalize 1, 2
Monitoring Protocol
- High-risk patients:
- Monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours for first 3 days
- Then monitor every 24 hours subsequently
- Monitor vital signs (heart rate, blood pressure, urine output, respiratory rate) regularly 1
Evidence of Efficacy
Rasburicase has demonstrated superior efficacy in preventing TLS compared to allopurinol alone. In clinical studies, rasburicase rapidly reduced uric acid levels within 4 hours of administration, with 96% of patients achieving uric acid levels ≤2 mg/dL by this timepoint 3. A comparative study showed only 2.6% of patients receiving urate oxidase required dialysis compared to 16% of those receiving allopurinol 1.
Common Pitfalls and Caveats
Avoid concurrent administration of allopurinol and rasburicase, as this reduces rasburicase efficacy by decreasing substrate availability 1, 2
Do not alkalinize urine in patients receiving rasburicase therapy 1
Screen for G6PD deficiency before administering rasburicase, especially in patients of African, Mediterranean, or Southeast Asian descent 2, 3
Do not delay chemotherapy unnecessarily - rasburicase allows for earlier administration of chemotherapy when needed due to rapid uric acid degradation 1
Consider nephrology consultation before restarting therapy in patients with previous episodes of clinical TLS 1
By following this structured approach to TLS prophylaxis based on patient risk stratification, clinicians can significantly reduce morbidity and mortality associated with this potentially life-threatening complication of cancer therapy.