In an older, underweight patient with advanced Hodgkin lymphoma about to receive cytotoxic chemotherapy who has a uric acid level of 8 mg/dL and possible renal impairment, what tumor‑lysis‑syndrome prophylaxis should be initiated?

Tumor Lysis Syndrome Prophylaxis in Advanced Hodgkin Lymphoma with Hyperuricemia

Immediate Recommendation

This patient requires rasburicase 0.20 mg/kg IV over 30 minutes, starting at least 4 hours before chemotherapy, combined with aggressive IV hydration targeting urine output ≥100 mL/hour. 1

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Risk Stratification Justifies High-Risk Management

Your patient meets multiple high-risk criteria for tumor lysis syndrome:

• Pre-existing hyperuricemia (8 mg/dL exceeds the pediatric threshold of >8 mg/dL that defines critical hyperuricemia) 2
• Possible renal impairment (a host factor placing patients at high TLS risk) 1
• Advanced Hodgkin lymphoma (bulky disease is a recognized risk factor) 1
• Underweight status (suggests poor physiologic reserve and potential volume depletion) 3
• Older age (an independent comorbidity predisposing to TLS) 3

The European Hematology Association explicitly states that adult patients with uric acid >10 mg/dL require rasburicase, but your patient's 8 mg/dL level combined with renal impairment and advanced disease elevates the risk profile to warrant rasburicase rather than allopurinol alone. 2

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Why Rasburicase Over Allopurinol

Allopurinol Cannot Lower Existing Hyperuricemia

• Allopurinol only prevents new uric acid formation by blocking xanthine oxidase; it cannot reduce the 8 mg/dL already present in the bloodstream. 1, 4
• Your patient needs immediate reduction of pre-existing uric acid before chemotherapy-induced tumor lysis adds to the burden. 1

Superior Efficacy Data

• In the pivotal randomized trial, rasburicase achieved 86% reduction in plasma uric acid within 4 hours, versus only 12% with allopurinol (p<0.0001). 1
• Mean uric acid area-under-curve was 128±70 mg·dL⁻¹·hour with rasburicase versus 329±129 mg·dL⁻¹·hour with allopurinol (p<0.001). 1
• In a retrospective pediatric cohort, only 2.6% of rasburicase patients required dialysis versus 16% of allopurinol patients. 1

Renal Impairment Complicates Allopurinol Use

• Allopurinol and its active metabolite oxipurinol are renally excreted and accumulate in renal insufficiency, requiring ≥50% dose reduction. 1, 4
• Your patient's possible renal impairment makes allopurinol both less effective (impaired clearance of uric acid) and more toxic (drug accumulation). 1

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Rasburicase Dosing Protocol

Pre-Treatment Screening (Mandatory)

• Screen for G6PD deficiency before the first dose; rasburicase causes life-threatening hemolysis and methemoglobinemia in G6PD-deficient patients. 1, 5
• Confirm no history of severe hypersensitivity to rasburicase. 1
• Verify the patient is not pregnant or lactating. 1

Standard Regimen

• Dose: 0.20 mg/kg IV over 30 minutes once daily 1, 5
• Timing: First dose ≥4 hours before starting chemotherapy 1
• Duration: 3–5 days, then transition to oral allopurinol 1

Critical Sequencing Rule

• Never give allopurinol concurrently with rasburicase; simultaneous use causes xanthine accumulation and crystal-induced obstructive uropathy. 1
• After rasburicase is completed, start allopurinol 100 mg/m² PO every 8 hours (maximum 800 mg/day) for 3–7 days. 1
• In renal impairment, reduce allopurinol dose by ≥50%. 1

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Aggressive Hydration (Essential Adjunct)

• Initiate ≥48 hours before chemotherapy when feasible. 2
• Target ≥2–3 L/m²/day IV hydration (use quarter-normal saline/5% dextrose). 1, 2
• Goal urine output: ≥100 mL/hour in adults. 1, 2
• Exclude potassium, calcium, and phosphate from initial fluids to avoid exacerbating electrolyte derangements. 1
• Add loop diuretics (not thiazides) if urine output targets are not met, provided no obstructive uropathy or hypovolemia. 1, 2

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Monitoring Protocol

During Rasburicase Therapy

• Measure uric acid, potassium, phosphorus, calcium, creatinine, and LDH every 6 hours for the first 24 hours, then every 12 hours for 3 days. 2
• Place blood samples immediately on ice to prevent ex vivo uric acid degradation by residual rasburicase, which falsely lowers measured levels. 1

Redosing Criteria

• Continue rasburicase only if uric acid remains >4 mg/dL at 12–24 hours after the initial dose; treatment is unnecessary when uric acid becomes undetectable. 1

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Common Pitfalls to Avoid

Starting Allopurinol Instead of Rasburicase

• Allopurinol monotherapy in a patient with existing hyperuricemia (8 mg/dL) and renal impairment leaves the patient vulnerable to acute uric acid nephropathy when chemotherapy triggers massive tumor lysis. 1, 2

Inadequate Hydration

• Failing to achieve target urine output ≥100 mL/hour compromises rasburicase effectiveness and increases crystal deposition risk. 1

Delaying Rasburicase Until After Chemotherapy

• The first rasburicase dose must be given ≥4 hours before tumor-specific therapy to preemptively lower uric acid before the lysis surge. 1, 2

Correcting Mild Hypocalcemia

• Do not give calcium gluconate for asymptomatic hypocalcemia; it promotes calcium-phosphate precipitation in kidneys and tissues. 1, 2

Concurrent Allopurinol and Rasburicase

• This combination causes xanthine crystal deposition in renal tubules, leading to obstructive uropathy. 1

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Inpatient Setting Required

• High-risk TLS prophylaxis should be delivered in a hospital with immediate dialysis access and a pre-arranged nephrology consultation. 1
• Continuous ECG monitoring is essential if hyperkalemia develops. 2

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Transition to Allopurinol After Rasburicase

Once rasburicase is completed (typically after 3–5 days and uric acid is controlled):

• Start allopurinol 100 mg/m² PO every 8 hours (maximum 800 mg/day). 1
• In renal impairment, reduce dose by ≥50%. 1
• Continue for 3–7 days based on ongoing TLS risk. 1
• Monitor uric acid daily until stable. 1

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Dialysis Indications

Initiate renal replacement therapy if any of the following develop despite medical management: 2

• Persistent hyperkalemia unresponsive to insulin/glucose and sodium polystyrene
• Severe metabolic acidosis
• Volume overload unresponsive to diuretics
• Overt uremic symptoms
• Severe progressive hyperphosphatemia (>6 mg/dL)
• Severe symptomatic hypocalcemia

Intermittent hemodialysis removes uric acid effectively (≈50% reduction per 6-hour session), but daily dialysis is often required due to continuous metabolite release from lysed tumor cells. 2