What is the best approach for tumor lysis syndrome prophylaxis and monitoring of liver and renal function in a patient with a high white blood cell count, potential diagnosis of polycythemia vera, and mildly coarsened liver echotexture?

Tumor Lysis Syndrome Prophylaxis and Monitoring in High WBC with Liver Dysfunction

Given the high white blood cell count and potential polycythemia vera diagnosis, this patient requires rasburicase prophylaxis with aggressive hydration, and comprehensive metabolic monitoring every 12 hours for the first 3 days, with particular attention to renal function given the coexisting liver abnormality. 1

Risk Stratification

This patient falls into the high-risk category for tumor lysis syndrome (TLS) based on:

• WBC >100 × 10⁹/L is an established high-risk criterion requiring rasburicase prophylaxis 1
• Myeloproliferative disorders like polycythemia vera carry inherent risk for TLS when cytoreductive therapy is initiated 1
• The mildly coarsened liver echotexture suggests hepatic dysfunction, which may impair uric acid metabolism and increase TLS risk 1

TLS Prophylaxis Protocol

Rasburicase Administration

Rasburicase should be administered at 0.20 mg/kg/day as a 30-minute infusion, starting at least 4 hours before initiating cytoreductive therapy and continuing for 3-5 days. 1, 2

• Rasburicase is the preferred agent for high-risk patients (WBC >100,000/mcL) and achieves uric acid levels ≤2 mg/dL in 96% of patients within 4 hours 2
• Do not administer allopurinol concurrently with rasburicase to avoid xanthine accumulation and lack of substrate for rasburicase 1
• After completing rasburicase, transition to oral allopurinol 100 mg/m² three times daily (maximum 800 mg/day) 1

Contraindications to Screen For

Before administering rasburicase, verify the patient does not have:

• G6PD deficiency (causes hemolytic anemia) 1
• Methemoglobinemia 1
• History of severe hypersensitivity reactions 2

If contraindicated, use allopurinol with hydration and urine alkalinization instead 1

Hydration Strategy

Initiate aggressive intravenous hydration at 3 L/m² per day, targeting urine output ≥100 mL/hour in adults (3 mL/kg/hour if <10 kg). 1

• Hydration should ideally begin 48 hours before cytoreductive therapy 1
• Monitor urine osmolality and fractional excretion of sodium to assess hydration status 1
• Loop diuretics may be required to maintain urine output, but only after confirming adequate hydration and absence of obstructive uropathy 1
• Do not alkalinize urine when using rasburicase 1

Special Consideration for Liver Dysfunction

The mildly coarsened liver echotexture warrants caution:

• Monitor for fluid overload more closely, as hepatic dysfunction may impair fluid handling 1
• Intractable fluid overload is an indication for renal dialysis 1

Comprehensive Metabolic Monitoring

Initial 72 Hours (High-Risk Period)

Monitor every 12 hours: 1

• Uric acid
• Electrolytes: potassium, phosphorus, calcium, sodium
• Renal function: creatinine, BUN
• LDH
• Complete blood count

After 72 Hours

Monitor every 24 hours: 1

• All above parameters
• Continue until TLS risk has resolved (typically 5-7 days after initiating therapy)

Liver Function Monitoring

Given the coarsened liver echotexture, obtain baseline and serial monitoring of: 1

• Comprehensive metabolic panel including liver enzymes (AST, ALT, alkaline phosphatase, bilirubin)
• Albumin
• Coagulation parameters if thrombocytosis is present (>1000 × 10⁹/L) to monitor for acquired von Willebrand syndrome 3

A complete metabolic panel with uric acid and LDH must be performed before initiating ruxolitinib or other cytoreductive therapy, every 2-4 weeks until doses are stabilized, then as clinically indicated. 1

Renal Function Assessment

Use estimated glomerular filtration rate (eGFR) rather than serum creatinine alone to assess renal function, as creatinine is inadequate in this setting due to variability with age, hydration, and muscle mass. 1

Calculate eGFR using MDRD formula: 1

• eGFR (mL/min/1.73 m²) = 175 × (serum creatinine (mmol/L) × 0.0113)^-1.154 × age (years)^-0.203 × (0.742 if female)

Rasburicase should be considered as initial treatment in patients with rapidly increasing blast counts, high uric acid, and evidence of impaired renal function. 1

Indications for Renal Dialysis

Initiate dialysis for: 1

• Intractable fluid overload
• Hyperkalemia refractory to medical management
• Hyperuricemia refractory to rasburicase
• Hyperphosphatemia refractory to phosphate binders
• Symptomatic hypocalcemia

Additional Supportive Measures

Cytoreductive Therapy Considerations

• Consider hydroxyurea for immediate WBC reduction before definitive therapy if leukostasis symptoms develop (hypoxia, neurological symptoms, renal failure, cardiac ischemia) 1
• Leukapheresis may be used for symptomatic leukostasis but should not substitute for prompt initiation of definitive therapy 1

Infection Prophylaxis

Implement comprehensive antimicrobial prophylaxis: 1

• Antibacterial prophylaxis per institutional guidelines
• Antifungal prophylaxis (note: avoid azoles during anthracycline chemotherapy as they impair drug metabolism and increase toxicity) 1
• Antiviral prophylaxis
• Consider intrathecal prophylaxis if WBC count is very high (risk of CNS infiltration) 1

Common Pitfalls to Avoid

1. Do not delay rasburicase waiting for laboratory confirmation of hyperuricemia in high-risk patients—prophylaxis should begin before cytoreductive therapy 1, 4

2. Do not combine allopurinol with rasburicase during the initial treatment phase 1

3. Do not rely on serum creatinine alone for renal assessment—calculate eGFR 1

4. Do not alkalinize urine when using rasburicase (no longer recommended and contraindicated with rasburicase) 1

5. Do not overlook G6PD screening before rasburicase administration 1, 2

6. Monitor for hepatotoxicity given baseline liver abnormality, especially if using myelosuppressive agents 1