Treatment for Tumor Lysis Syndrome
Immediate Management Based on Risk Level
For moderate to high-risk patients, initiate aggressive IV hydration through central venous access combined with rasburicase 0.20 mg/kg/day infused over 30 minutes for 3-5 days—do not use allopurinol in this population. 1, 2, 3
Risk-Stratified Treatment Algorithm
High-Risk Patients
High-risk patients include those with bulky high-grade lymphomas, acute lymphoblastic leukemia, WBC >100×10⁹/L, elevated LDH >2 times upper normal limit, pre-existing renal impairment, or hyperuricemia >8 mg/dL. 2
Treatment protocol:
- Start aggressive IV hydration 48 hours before chemotherapy when possible, targeting urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg). 1, 2, 3
- Administer rasburicase 0.20 mg/kg/day IV over 30 minutes for 3-5 days—this is superior to allopurinol because it converts existing uric acid to allantoin (5-10 times more soluble), providing immediate reduction of pre-existing hyperuricemia. 4, 1, 5
- Use central venous access for reliable fluid administration in all high-risk cases. 1
- Add loop diuretics (furosemide) only if target urine output cannot be achieved, but avoid in patients with obstructive uropathy or hypovolemia. 1, 3
Moderate-Risk Patients
Treatment protocol:
- Initiate aggressive IV hydration at 3 L/m²/day. 2, 3
- Administer either rasburicase 0.20 mg/kg/day IV or allopurinol 300 mg orally once daily (100 mg/m² three times daily in children, maximum 800 mg/day). 2, 3
- The choice between rasburicase and allopurinol depends on baseline uric acid levels and renal function—if uric acid is already elevated or renal function is compromised, rasburicase is preferred. 1, 2
Low-Risk Patients
Critical Medication Considerations
Never administer rasburicase concurrently with allopurinol—this causes xanthine accumulation and eliminates the substrate rasburicase needs to function. 1, 2
Rasburicase is contraindicated in patients with G6PD deficiency due to risk of severe hemolysis and methemoglobinemia—screen patients of African or Mediterranean ancestry before administration. 5
Do not use urine alkalinization in patients receiving rasburicase—it increases calcium phosphate precipitation risk without improving outcomes. 1, 3
Management of Metabolic Abnormalities
Hyperkalemia
- Mild (<6 mmol/L, asymptomatic): Treat with hydration, loop diuretics, and sodium polystyrene 1 g/kg orally or by enema. 1, 3
- Severe (≥6 mmol/L): Administer rapid insulin 0.1 units/kg plus 25% dextrose 2 mL/kg, calcium carbonate 100-200 mg/kg/dose to stabilize myocardial membranes, and sodium bicarbonate to correct acidosis. 1, 3
- Continuous ECG monitoring is mandatory for severe hyperkalemia. 1, 2, 3
Hyperphosphatemia
- Mild (<1.62 mmol/L): No treatment required or aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric). 1
- Monitor closely as hyperphosphatemia drives secondary hypocalcemia. 2
Hypocalcemia
- Asymptomatic: No treatment required—avoid calcium supplementation as it increases tissue and renal precipitation of calcium phosphate. 1, 2
- Symptomatic (tetany, seizures): Calcium gluconate 50-100 mg/kg as single IV dose, cautiously repeated if necessary. 1, 3
Monitoring Protocol
High-Risk Patients
Monitor every 12 hours for the first 3 days, then every 24 hours, measuring: 1, 2, 3
- Vital signs
- Serum uric acid
- Electrolytes (potassium, phosphorus, calcium, sodium)
- Renal function (creatinine, BUN, calculated eGFR using MDRD or Cockcroft-Gault—do not rely on creatinine alone) 2
- LDH
- Urine output
Established TLS
Monitor every 6 hours for the first 24 hours, then daily for the same parameters. 1, 2
Indications for Renal Replacement Therapy
Initiate dialysis immediately for: 1, 2, 3
- 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 unresponsive to diuretics
- Symptomatic uremia
Hemodialysis reduces plasma uric acid by approximately 50% with each 6-hour treatment (clearance 70-100 mL/min). 2, 3
Critical Pitfalls to Avoid
- Do not delay treatment while waiting for laboratory confirmation—mortality reaches 83% in untreated clinical TLS versus 24% in those without TLS. 2, 3
- Do not use serum creatinine alone to assess renal function—always calculate eGFR using MDRD or Cockcroft-Gault equations, as creatinine is a delayed marker of acute kidney injury. 2
- Do not collect uric acid samples improperly—rasburicase enzymatically degrades uric acid in blood samples at room temperature; collect in pre-chilled heparin tubes and immediately immerse in ice water bath, assaying within 4 hours. 5
- Do not use rasburicase for more than one course of treatment—it is indicated only for a single course. 5