What is tumor lysis syndrome?

Tumor Lysis Syndrome: Definition, Diagnosis, and Management

Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic disorder characterized by massive and abrupt release of cellular components into the blood after rapid lysis of malignant cells, resulting in hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and associated clinical complications. 1

Definition and Classification

• TLS is classified into laboratory TLS (LTLS) and clinical TLS (CTLS) 1
• Laboratory TLS is defined by the presence of two or more abnormal serum values (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia) within three days before or seven days after initiation of anticancer therapy 1
• Clinical TLS requires laboratory TLS plus one or more clinical complications such as renal insufficiency, cardiac arrhythmias, or seizures 2

Pathophysiology

• TLS occurs when tumor cells undergo rapid lysis, releasing intracellular contents including nucleic acids, proteins, phosphorus, and potassium into the bloodstream 2
• Released nucleic acids are catabolized to hypoxanthine, then xanthine, and finally to uric acid by xanthine oxidase 2
• Uric acid precipitation in renal tubules can lead to renal insufficiency or failure 2
• Hyperkalemia can produce cardiac irregularities including arrhythmias, ventricular tachycardia, fibrillation, or cardiac arrest 2

Risk Factors

Host-Related Factors

• Pre-existing elevated uric acid levels 2
• Pre-existing renal dysfunction 2
• Advanced age 2
• Dehydration 3
• Hyponatremia 3
• Obstructive uropathy 3

Disease-Related Factors

• High-grade hematologic malignancies with rapid proliferation rates (Burkitt's lymphoma, ALL, AML) 1
• Bulky disease with large tumor burden 2
• Extensive bone marrow involvement 2
• High tumor sensitivity to chemotherapy 2
• Elevated LDH levels 2

Treatment-Related Factors

• Intensive polychemotherapy including cisplatin, cytosine arabinoside, etoposide 3
• Highly active, cycle-specific drugs 2
• Corticosteroids (often used in highly proliferating lymphoid disorders) 2

Clinical Manifestations

• Common symptoms include nausea, vomiting, diarrhea, anorexia, lethargy, edema, fluid overload, and hematuria 1
• Severe manifestations may include congestive heart failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, and possible sudden death 1
• Renal failure is a common complication due to uric acid crystal formation in renal tubules 2

Diagnosis

• Diagnosis is based on laboratory findings and clinical manifestations 1
• Laboratory parameters to monitor include:
  • Uric acid (hyperuricemia)
  • Potassium (hyperkalemia)
  • Phosphorus (hyperphosphatemia)
  • Calcium (hypocalcemia)
  • Creatinine (elevated) 1

Prevention and Management

Risk Stratification

• High-risk patients: Those with bulky, rapidly proliferating tumors highly sensitive to chemotherapy 2
• Intermediate-risk patients: Less bulky disease or less sensitive to therapy 2
• Low-risk patients: Small tumor burden or less aggressive malignancies 2

Prevention Strategies

• High-risk patients should receive hydration and rasburicase 2
• Intermediate-risk patients should receive hydration plus either allopurinol or rasburicase 2
• Low-risk patients should receive hydration and oral allopurinol 2

Specific Interventions

Hydration

• Aggressive hydration should be started 48 hours before tumor-specific therapy when possible 3
• Goal: maintain urine output ≥100 mL/hour in adults 3
• Promotes excretion of uric acid and phosphate by improving intravascular volume, renal blood flow, and glomerular filtration 1

Hypouricemic Agents

• Allopurinol: Blocks xanthine oxidase activity, preventing conversion of hypoxanthine and xanthine to uric acid 2

  • Dosage: 300 mg orally once daily 2
  • Prevents formation of new uric acid but does not reduce existing uric acid 2

• Rasburicase: Recombinant urate-oxidase enzyme that converts existing uric acid to allantoin 2

  • Dosage: 0.20 mg/kg/day, infused over 30 minutes for 3-5 days 3
  • Allows for earlier administration of chemotherapy due to rapid degradation of uric acid 3
  • More effective than allopurinol in rapidly reducing uric acid levels 4

Management of Electrolyte Abnormalities

• Hyperphosphatemia: Treat with aluminum hydroxide 50-100 mg/kg/day divided in 4 doses 3
• Hypocalcemia: Only treat if symptomatic with calcium gluconate 50-100 mg/kg 3
• Hyperkalemia: Treat with hydration, loop diuretics, and sodium polystyrene; severe cases may require insulin and glucose, calcium carbonate, and sodium bicarbonate 3

Monitoring

• High-risk patients should be monitored every 12 hours for the first three days, then every 24 hours 3
• Patients with established TLS should be monitored every 6 hours for the first 24 hours, then daily 3
• Parameters to monitor include vital signs, serum uric acid, electrolytes, and renal function 3

Indications for Dialysis

• Severe oliguria or anuria 3
• Persistent hyperkalemia 3
• Hyperphosphatemia with symptomatic hypocalcemia 3
• Hyperuricemia not responding to rasburicase 3
• Severe volume overload 3

Important Considerations and Pitfalls

• Urine alkalinization is not recommended in patients receiving rasburicase 3
• Calcium gluconate should not be used to correct mild hypocalcemia as it may lead to increased tissue and renal precipitation of calcium phosphate 3
• Allopurinol should not be administered concurrently with rasburicase to avoid xanthine accumulation 3
• Rasburicase can cause severe hypersensitivity reactions including anaphylaxis in approximately 4.3% of patients 4
• Rasburicase is contraindicated in patients with G6PD deficiency due to risk of hemolysis 4
• Early recognition and intervention are critical to prevent life-threatening complications 1