What are the symptoms and treatment options for a patient with tumor lysis syndrome, particularly those with bulky disease or high white blood cell counts?

Symptoms of Tumor Lysis Syndrome

Tumor lysis syndrome presents with metabolic derangements (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia) that can rapidly progress to life-threatening complications including cardiac arrhythmias, acute kidney injury, seizures, and death—particularly dangerous in patients with bulky disease or high white blood cell counts who face mortality rates approaching 35% in solid tumors. 1, 2

Clinical Manifestations

Metabolic Abnormalities

Laboratory TLS requires at least 2 of the following 4 metabolic derangements occurring within 3 days before or 7 days after chemotherapy initiation: 3

• Hyperuricemia (>8 mg/dL in adults) results from massive nucleic acid breakdown and can cause uric acid crystallization in renal collecting ducts, leading to acute oliguric renal failure 2, 3
• Hyperkalemia (≥6 mmol/L is life-threatening) occurs from rapid release of intracellular potassium, exacerbated by concurrent renal failure that impairs potassium excretion 4, 3
• Hyperphosphatemia develops from tumor cell lysis and can precipitate with calcium, worsening renal injury 1, 3
• Hypocalcemia results from calcium-phosphate precipitation in tissues 3

Cardiovascular Symptoms

• Cardiac arrhythmias including ventricular tachycardia and fibrillation manifest as palpitations and represent the most immediately life-threatening complication 4, 3
• In Burkitt's lymphoma cohorts, 2 of 4 deaths were directly attributable to hyperkalemia-induced cardiac complications 4
• Clinical TLS with significant hyperkalemia carries an 83% mortality rate compared to 24% without clinical TLS 4

Renal Manifestations

• Acute kidney injury (creatinine ≥1.5 times upper normal limit or eGFR ≤60 mL/min) develops from uric acid crystallization and calcium-phosphate deposition in renal tubules 2, 3
• Oliguria or anuria occurs when uric acid crystals obstruct collecting ducts and deep cortical vessels 1, 3

Neuromuscular Symptoms

• Muscle cramps and paresthesias result from hyperkalemia-induced neuromuscular effects 4
• Seizures occur from severe hypocalcemia or metabolic encephalopathy 3
• Tetany manifests with symptomatic hypocalcemia 1, 3
• Uremic encephalopathy develops in severe cases with advanced renal failure 3

Gastrointestinal Symptoms

• Nausea and vomiting occur as part of the general metabolic derangement, particularly when combined with hyperkalemia 4

High-Risk Features Requiring Vigilance

Patients with the following characteristics face substantially elevated TLS risk and warrant aggressive prophylaxis: 1, 2

• Bulky disease with tumor burden, especially with massive liver metastases 1, 2
• Elevated LDH >2 times upper normal limit, reflecting high tumor burden 1, 2
• High white blood cell counts >50,000/mm³ 3
• Pre-existing renal impairment or obstructive uropathy 1, 2
• Baseline hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults) 2
• Highly chemosensitive malignancies including Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (26.4% TLS incidence) 2, 3

Immediate Management Priorities

For Clinical TLS (Laboratory TLS + Organ Dysfunction)

Hydration and rasburicase should be administered immediately to all patients with clinical TLS. 1, 3

• Aggressive IV hydration at 3 L/m²/day (minimum 2 L/m²/day) to maintain urine output ≥100 mL/hour 1, 2
• Rasburicase 0.20 mg/kg/day IV over 30 minutes rapidly converts uric acid to allantoin (5-10 times more soluble), achieving uric acid ≤2 mg/dL in 96% of patients within 4 hours 1, 5

For Severe Hyperkalemia (≥6 mmol/L)

Immediate interventions to prevent fatal arrhythmias: 1, 4, 3

• Calcium carbonate 100-200 mg/kg/dose IV to stabilize myocardial cell membranes 1, 4
• Rapid insulin 0.1 units/kg IV plus 25% dextrose 2 mL/kg IV to shift potassium intracellularly 1, 3
• Continuous ECG monitoring is mandatory for all hyperkalemic patients 1
• Sodium polystyrene 1 g/kg orally or by enema for mild hyperkalemia (<6 mmol/L) 1, 3

For Symptomatic Hypocalcemia

• Calcium gluconate 50-100 mg/kg IV over 2-5 minutes for tetany or seizures, repeated cautiously if necessary 1, 3
• Critical caveat: Never treat asymptomatic hypocalcemia, as calcium administration precipitates calcium-phosphate crystals in tissues and worsens renal injury 1, 3

For Hyperphosphatemia

• Mild hyperphosphatemia (<1.62 mmol/L) requires no treatment 1, 3
• Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses for more severe elevations 1

Indications for Emergency Hemodialysis

Initiate hemodialysis urgently when: 1, 3

• Oliguria or anuria persists despite aggressive hydration 1, 3
• Severe refractory hyperkalemia unresponsive to medical management 1, 4
• Symptomatic hypocalcemia refractory to treatment 3
• Severe hyperphosphatemia with calcium-phosphate precipitation 3
• Hyperuricemia unresponsive to rasburicase 2

Hemodialysis achieves uric acid clearance of 70-100 mL/min, reducing plasma uric acid by approximately 50% with each 6-hour treatment, often restarting diuresis when levels fall to 10 mg/dL 1

Monitoring Requirements

Intensive laboratory monitoring is essential: 3

• Potassium every 2-4 hours after initial treatment 3
• Uric acid, electrolytes, phosphate, calcium every 6 hours for the first 24 hours 3
• Continuous ECG monitoring for all patients with hyperkalemia 1

Critical Pitfalls to Avoid

• Never use loop diuretics in patients with anuria or established oliguria despite adequate hydration 3
• Never treat asymptomatic hypocalcemia, as this precipitates calcium-phosphate crystals and worsens renal injury 1, 3
• Never delay rasburicase in high-risk patients—the mortality rate in solid tumors approaches 35%, likely due to delayed recognition and less aggressive prophylactic measures compared to hematologic malignancies 1, 2