What is the treatment and prevention for tumor lysis syndrome in patients with leukemia or lymphoma undergoing chemotherapy?

Tumor Lysis Syndrome: Treatment and Prevention

Immediate Risk Stratification and Management Algorithm

For patients with leukemia or lymphoma undergoing chemotherapy, high-risk patients must receive aggressive hydration plus rasburicase, while low-risk patients should receive hydration plus oral allopurinol. 1

Risk Classification

High-risk patients include those with: 1, 2

• Burkitt's lymphoma or B-cell acute lymphoblastic leukemia
• Acute myeloid leukemia with WBC >100 × 10⁹/L
• Bulky disease (lymph nodes >5 cm)
• Elevated LDH >2 times upper normal limit
• Pre-existing renal impairment or hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults)
• High tumor burden with extensive bone marrow involvement

Low-risk patients include those with: 1

• Chronic lymphocytic leukemia (TLS rate only 0.42%)
• Small tumor burden
• Normal baseline renal function and uric acid levels
• Indolent lymphomas without bulky disease

Prevention Protocol by Risk Level

High-Risk Patients (Inpatient Setting Required)

Initiate aggressive hydration 48 hours before chemotherapy when possible: 1, 2

• Target urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg)
• Administer 3 L/m²/day IV hydration through central venous access
• Loop diuretics may be required to maintain urine output (contraindicated in hypovolemia or obstructive uropathy)

Administer rasburicase as primary prophylaxis: 1, 3

• Dose: 0.20 mg/kg/day IV over 30 minutes for 3-5 days
• Give first dose at least 4 hours before starting chemotherapy
• Critical contraindications: G6PD deficiency (screen patients of African or Mediterranean ancestry), history of anaphylaxis to rasburicase, pregnancy
• Never administer rasburicase concurrently with allopurinol to avoid xanthine accumulation and substrate depletion 4

Low-Risk Patients (May Be Outpatient)

Administer oral allopurinol: 1, 2

• Dose: 100 mg/m² three times daily (maximum 800 mg/day orally)
• Start 1-2 days before chemotherapy, continue 3-7 days after
• Reduce dose by 50% in renal insufficiency due to drug accumulation 4

Provide vigorous hydration: 1

• Target ≥2 L/m²/day
• Maintain urine output >100 mL/hour

Critical Management Caveat: Urinary Alkalinization

Urinary alkalinization with sodium bicarbonate is NOT recommended. 1 While historically used with allopurinol, alkalinization increases risk of calcium phosphate precipitation and metabolic alkalosis without substantially improving xanthine solubility. Increasing urine flow rate is far more effective than pH manipulation for preventing uric acid crystallization.

Treatment of Established Tumor Lysis Syndrome

Immediate Interventions

All patients with clinical TLS or worsening laboratory TLS require: 1, 2

• Immediate rasburicase 0.20 mg/kg/day IV (even if previously on allopurinol)
• Aggressive IV hydration at 3 L/m²/day
• Transfer to intensive care unit for high-risk patients
• Continuous cardiac monitoring for hyperkalemia

Monitoring Protocol

High-risk patients: 2, 5

• Monitor every 12 hours for first 3 days: uric acid, potassium, phosphate, calcium, creatinine, BUN, LDH
• Then every 24 hours until resolution
• Continuous ECG monitoring if hyperkalemic

Patients with established TLS: 2

• Monitor every 6 hours for first 24 hours
• Critical specimen handling: Place blood samples immediately on ice in prechilled heparin tubes; assay within 4 hours to prevent ex vivo uric acid degradation by rasburicase 3

Management of Specific Electrolyte Abnormalities

Hyperkalemia (most immediately life-threatening): 1

• Verify with second sample to rule out pseudohyperkalemia from hemolysis
• Continuous ECG monitoring
• Calcium gluconate 100-200 mg/kg IV slowly with ECG monitoring for life-threatening arrhythmias
• Do not administer sodium bicarbonate and calcium through same IV line

Hyperphosphatemia: 1

• Avoid phosphate-containing foods and medications
• Phosphate binders if persistent elevation
• Monitor for symptomatic hypocalcemia

Hypocalcemia: 1

• Treat only if symptomatic (tetany, seizures, arrhythmias)
• Calcium gluconate 50-100 mg/kg IV slowly with ECG monitoring
• Caution: Calcium administration with elevated phosphate increases calcium phosphate precipitation risk

Indications for Dialysis

Initiate renal replacement therapy for: 1, 2

• 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
• Symptomatic uremia

Hemodialysis effectively removes uric acid (clearance 70-100 mL/min) and phosphate, with plasma uric acid falling approximately 50% with each 6-hour treatment. 2 A nephrology consultation should be obtained immediately for high-risk patients before starting chemotherapy.

Common Pitfalls to Avoid

Never use rasburicase in G6PD-deficient patients - causes life-threatening hemolysis and methemoglobinemia. 3 Screen high-risk populations (African, Mediterranean ancestry) before administration.

Never give allopurinol and rasburicase concurrently - allopurinol blocks xanthine oxidase, causing xanthine accumulation while rasburicase depletes its substrate (uric acid). 4 If transitioning from rasburicase to allopurinol, wait until rasburicase course is complete.

Never delay chemotherapy to "wait and see" in high-risk patients - mortality rate is 83% with clinical TLS versus 24% without TLS in acute leukemia. 2, 5 Aggressive prophylaxis must begin before chemotherapy initiation.

Never forget to adjust allopurinol dose in renal impairment - failure to reduce by 50% leads to drug and metabolite accumulation with increased toxicity. 4

Never use thiazide diuretics - only loop diuretics are appropriate for maintaining urine output in TLS. 4

Evidence Quality Note

The recommendations prioritize the 2008 consensus guidelines from the Journal of Clinical Oncology 1 and Haematologica 1, which represent the highest-quality evidence-based reviews endorsed by major oncology societies (ASCO, European Society for Medical Oncology, Italian Society of Hematology). The FDA label for rasburicase 3 provides critical safety information that supersedes other recommendations regarding contraindications and monitoring. While these guidelines are from 2008, they remain the definitive standard as no higher-quality guidelines have superseded them, and the fundamental management principles (hydration, rasburicase for high-risk, allopurinol for low-risk) remain unchanged in clinical practice.