What is the management of tumor lysis syndrome?

Management of Tumor Lysis Syndrome

Begin aggressive IV hydration 48 hours before chemotherapy when possible, targeting urine output ≥100 mL/hour in adults, and administer rasburicase 0.20 mg/kg/day as the primary prophylactic and treatment agent—not allopurinol—in all high-risk patients. 1

Risk Stratification

Identify high-risk patients by assessing three categories of factors:

Host-related factors: 1

• Dehydration
• Hyponatremia
• Pre-existing renal impairment
• Obstructive uropathy
• Baseline hyperuricemia

Disease-related factors: 1

• Bulky disease
• High-grade lymphomas
• Acute lymphoblastic leukemia
• Elevated LDH

Therapy-related factors: 1

• Intensive polychemotherapy regimens
• Cisplatin, cytosine arabinoside, etoposide, or methotrexate

Primary Treatment Algorithm

Hydration Protocol

Establish central venous access for reliable fluid administration in high-risk patients. 1 Start aggressive IV hydration 48 hours before tumor-specific therapy, maintaining urine output at ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg). 1 If target urine output cannot be achieved, add loop diuretics (furosemide 40-80 mg IV) or mannitol, except in patients with obstructive uropathy or hypovolemia. 1, 2

Rasburicase Administration

Rasburicase is superior to allopurinol because it converts existing uric acid to allantoin, providing immediate reduction of pre-existing hyperuricemia rather than merely preventing new uric acid formation. 1 Administer rasburicase at 0.20 mg/kg/day, infused over 30 minutes, and continue for 3-5 days. 1 In randomized trials, rasburicase achieved significantly lower mean uric acid area under the curve compared to allopurinol (p<0.001), with 96% of patients achieving uric acid levels ≤2 mg/dL within 4 hours of the first dose. 3

Critical caveat: Do not administer allopurinol concurrently with rasburicase, as this causes xanthine accumulation and eliminates the substrate rasburicase needs to function. 1 Do not use urine alkalinization in patients receiving rasburicase therapy. 1

Management of Metabolic Abnormalities

Hyperkalemia

For mild hyperkalemia (<6 mmol/L): 2

• Continue aggressive IV hydration
• Add loop diuretics (furosemide 40-80 mg IV) to enhance renal potassium excretion

For severe hyperkalemia (≥6 mmol/L or ECG changes): 1, 2

• Immediate: Calcium gluconate 10%: 50-100 mg/kg IV over 2-5 minutes to stabilize myocardial cell membrane (onset 1-3 minutes, duration 30-60 minutes)
• Concurrent: Rapid-acting insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg (onset 15-30 minutes, duration 4-6 hours)
• Additional: Calcium carbonate 100-200 mg/kg/dose and sodium bicarbonate
• Continuous ECG monitoring is mandatory 1, 2
• Recheck potassium every 2-4 hours after initial treatment 2

Hyperphosphatemia

For mild hyperphosphatemia (<1.62 mmol/L): No treatment required. 1

For hyperphosphatemia ≥1.62 mmol/L: Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses (oral or nasogastric). 1, 2

Hypocalcemia

For asymptomatic hypocalcemia: No treatment required. 1 Do not correct mild hypocalcemia with calcium gluconate, as this may lead to increased tissue and renal precipitation of calcium phosphate. 1

For symptomatic hypocalcemia (tetany, seizures): Calcium gluconate 50-100 mg/kg as single IV dose, cautiously repeated if necessary. 1

Hyperuricemia

Rasburicase remains the primary agent. 1, 3 In the subset of 61 patients with baseline uric acid ≥8 mg/dL, rasburicase maintained plasma uric acid control by 4 hours in 72%, by 24 hours in 80%, by 48 hours in 92%, and by 96 hours in 100% of patients. 3

Monitoring Protocol

High-risk patients (before TLS develops): 1

• Monitor every 12 hours for the first three days, then every 24 hours
• Measure: LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, calcium

Patients with established TLS: 1

• Monitor every 6 hours for the first 24 hours, then daily
• Measure: vital parameters, serum uric acid, electrolytes, renal function
• Continuous ECG monitoring for hyperkalemia 1, 2

Indications for Renal Replacement Therapy

Initiate hemodialysis for: 1

• Severe oliguria or anuria
• Persistent hyperkalemia despite medical management
• Hyperphosphatemia with symptomatic hypocalcemia
• Hyperuricemia not responding to rasburicase
• Severe volume overload

Hemodialysis reduces plasma uric acid levels by approximately 50% with each 6-hour treatment and is the most effective and reliable method for removing potassium from the body. 1, 2

Clinical TLS Definition

Clinical TLS is defined by changes in at least two or more laboratory parameters (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia) plus at least one of the following within 7 days of treatment: renal failure/injury, need for renal dialysis, serum creatinine increase >1.5 ULN, arrhythmia, or seizure. 3