What is tumor lysis syndrome, its diagnosis and management?

Tumor Lysis Syndrome: Diagnosis and Management

Tumor lysis syndrome (TLS) is a potentially life-threatening complication of massive cellular lysis in rapidly proliferating, bulky, or highly chemo-radiosensitive cancers that requires prompt recognition and treatment to prevent mortality. 1, 2

Definition and Classification

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

Risk Factors

• High-risk malignancies: Burkitt's lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and other high-grade hematologic malignancies 2
• Disease-related factors: bulky disease, high tumor burden, elevated LDH, and rapid proliferation rate 1
• Host-related factors: dehydration, hyponatremia, pre-existing renal impairment, obstructive uropathy, and hyperuricemia 1
• Therapy-related factors: intensive polychemotherapy including cisplatin, cytosine arabinoside, etoposide, and methotrexate 1

Clinical Manifestations

• Common symptoms: nausea, vomiting, diarrhea, anorexia, lethargy, edema, fluid overload, and hematuria 2
• Severe manifestations: congestive heart failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, and possible sudden death 2
• Metabolic abnormalities: hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia 3
• End-organ damage: renal failure, cardiac arrhythmias, and seizures 3

Diagnosis

• Laboratory findings: 2
  • Hyperuricemia (≥8 mg/dL)
  • Hyperkalemia (≥6 mEq/L)
  • Hyperphosphatemia (≥4.5 mg/dL)
  • Hypocalcemia (≤7 mg/dL)
• Clinical manifestations: 2
  • Renal insufficiency (creatinine ≥1.5 times upper limit of normal)
  • Cardiac arrhythmias
  • Seizures

Management Algorithm

Prevention in High-Risk Patients

1. Risk Assessment: Evaluate patient for risk factors before initiating anticancer therapy 1

2. Aggressive Hydration: 1, 2

   • Start 48 hours before tumor-specific therapy when possible
   • Maintain urine output at ≥100 mL/hour in adults
   • Target 3 L/m²/day of IV fluids

3. Prophylactic Therapy Based on Risk: 3, 1

   • High-risk patients: Hydration + rasburicase (0.20 mg/kg/day)
   • Intermediate-risk patients: Hydration + either allopurinol or rasburicase
   • Low-risk patients: Hydration + oral allopurinol

Management of Established TLS

1. Hyperuricemia Management: 1, 4

   • Rasburicase: 0.20 mg/kg/day, infused over 30 minutes for 3-5 days
   • Rapidly decreases plasma uric acid levels (86% reduction within 4 hours vs. 12% with allopurinol)
   • Allopurinol: For low-risk patients, 300 mg/day orally
   • Important: Do not administer allopurinol concurrently with rasburicase

2. Electrolyte Management: 1

   • Hyperkalemia: Hydration, loop diuretics, sodium polystyrene; for severe cases: insulin with glucose, calcium carbonate, sodium bicarbonate
   • Hyperphosphatemia: Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses
   • Hypocalcemia: Treat only if symptomatic with calcium gluconate 50-100 mg/kg

3. Renal Support: 1

   • Indications for renal replacement therapy:
     • Severe oliguria or anuria
     • Persistent hyperkalemia
     • Hyperphosphatemia with symptomatic hypocalcemia
     • Hyperuricemia not responding to rasburicase
     • Severe volume overload

Monitoring

• High-risk patients: Monitor every 12 hours for the first three days, then every 24 hours 1
• Patients with TLS: Monitor every 6 hours for the first 24 hours, then daily 1
• Parameters to monitor: LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, calcium, and vital signs 1, 2

Important Considerations and Pitfalls

• Do not alkalinize urine in patients receiving rasburicase therapy 1, 4
• Do not correct mild hypocalcemia with calcium gluconate as it may lead to increased tissue and renal precipitation of calcium phosphate 1
• Screen for G6PD deficiency before administering rasburicase to prevent hemolysis 4
• Rasburicase allows for earlier administration of chemotherapy due to rapid degradation of uric acid 4
• Spontaneous TLS can occur before treatment initiation, especially in highly proliferative malignancies 5
• Hemodialysis can reduce plasma uric acid levels by approximately 50% with each 6-hour treatment 1

By following this structured approach to diagnosis and management, the potentially fatal complications of TLS can be effectively prevented or treated, significantly improving patient outcomes.