Tumour Lysis Syndrome: Pathophysiology, Symptoms, and Interventions

Tumour Lysis Syndrome (TLS) is a potentially life-threatening condition that occurs when a large number of cancer cells are rapidly destroyed and release their contents into the bloodstream. This typically happens after the initiation of cancer treatment, such as chemotherapy, or spontaneously in some aggressive tumors. The release of intracellular components like potassium, phosphate, and nucleic acids can cause a range of metabolic disturbances, leading to complications such as kidney failure, arrhythmias, and seizures.

Causes of Tumour Lysis Syndrome

TLS is usually triggered by the treatment of certain types of cancers, particularly those that have a high cell turnover or are highly sensitive to chemotherapy. The main causes of TLS include:

  1. Cancer Treatments:
    • Chemotherapy: The rapid destruction of tumor cells due to chemotherapy drugs can overwhelm the body’s ability to clear the resulting byproducts. TLS is more common in cancers that have a large tumor burden or fast-growing characteristics.
    • Radiation Therapy: Radiation can also lead to rapid cell death in tumor tissues, contributing to TLS.
    • Immunotherapy: Some immune checkpoint inhibitors or targeted therapies can also cause TLS in highly responsive tumors.
  2. Tumor Characteristics:
    • High Tumor Burden: Cancers with large tumors or rapidly dividing cells (e.g., acute leukemia, high-grade lymphomas, Burkitt lymphoma) are more likely to cause TLS.
    • Aggressive Tumors: Tumors that grow quickly or have a high cell turnover, such as those in leukemia or lymphoma, are at higher risk for TLS.
  3. Spontaneous TLS:
    • Spontaneous tumor lysis may occur without treatment, particularly in lymphomas or leukemias that present with high cell proliferation rates.

Pathophysiology of Tumour Lysis Syndrome

When tumor cells die rapidly, they release their intracellular contents into the bloodstream, including:

  • Potassium: Potassium is released from the cells and can lead to hyperkalemia, a dangerous electrolyte imbalance that can cause arrhythmias or cardiac arrest.
  • Phosphate: Phosphate is released from the lysed cells, which can bind with calcium, leading to hypocalcemia (low calcium levels). The calcium-phosphate precipitates can damage the kidneys.
  • Nucleic Acids: The breakdown of nucleic acids releases uric acid, which can accumulate in the kidneys and cause uric acid nephropathy, a form of kidney damage.
  • Lactic Acid: The rapid cell death may also increase lactic acid production, leading to metabolic acidosis.

Symptoms of Tumour Lysis Syndrome

The signs and symptoms of TLS result from the metabolic disturbances caused by the rapid release of cellular contents. Symptoms can vary depending on the severity of the condition, but they may include:

  • Hyperkalemia (High Potassium Levels):
    • Cardiac arrhythmias (irregular heartbeats)
    • Weakness or fatigue
    • Nausea and vomiting
    • Cardiac arrest (in severe cases)
  • Hyperphosphatemia (High Phosphate Levels):
    • Nausea and vomiting
    • Itching (pruritus)
    • Muscle cramps
    • Risk of calcium-phosphate deposits in the kidneys leading to kidney damage
  • Hypocalcemia (Low Calcium Levels):
    • Tetany (muscle spasms)
    • Seizures
    • Tingling or numbness around the mouth and fingertips
    • Cardiac arrhythmias (particularly QT prolongation on ECG)
  • Hyperuricemia (High Uric Acid Levels):
    • Acute kidney injury due to uric acid deposition in the kidneys
    • Flank pain or hematuria (blood in urine)
    • Reduced urine output or anuria (complete cessation of urine production)
  • Metabolic Acidosis:
    • Fatigue
    • Tachypnea (rapid breathing)
    • Nausea
    • Confusion or lethargy

Diagnosis of Tumour Lysis Syndrome

The diagnosis of TLS is often based on clinical presentation, laboratory tests, and the patient’s underlying cancer diagnosis. Key diagnostic tests include:

  1. Laboratory Tests:
    • Serum Electrolytes: Testing for elevated potassium (hyperkalemia), phosphate (hyperphosphatemia), and uric acid (hyperuricemia). Low calcium (hypocalcemia) is also a hallmark of TLS.
    • Kidney Function Tests: Serum creatinine and blood urea nitrogen (BUN) levels to assess kidney function and potential renal failure.
    • Urinalysis: Presence of uric acid crystals in the urine can suggest kidney involvement.
  2. Diagnostic Criteria:
    • The Berlin definition for TLS includes:
      • Laboratory TLS: The presence of two or more of the following within 3 days before or 7 days after starting treatment:
        • Uric acid > 8 mg/dL or 25% increase from baseline
        • Potassium > 6 mmol/L or 25% increase from baseline
        • Phosphate > 4.5 mg/dL or 25% increase from baseline
        • Calcium < 7 mg/dL or 25% decrease from baseline
      • Clinical TLS: Evidence of renal failure, arrhythmias, seizures, or death due to TLS.

Treatment and Management of Tumour Lysis Syndrome

Early recognition and treatment of TLS are crucial to preventing severe complications, such as kidney failure or cardiac arrest. The main components of TLS management include:

1. Hydration:

  • Aggressive intravenous (IV) fluid administration is one of the most important steps to help prevent renal failure. Hydration helps dilute the levels of uric acid and phosphate, and it promotes renal excretion of these substances.
  • Alkalinization: In some cases, bicarbonate may be added to IV fluids to alkalinize the urine, making it less likely for uric acid to precipitate in the kidneys.

2. Medications:

  • Allopurinol: This medication inhibits the production of uric acid and is often used prophylactically to reduce the risk of hyperuricemia and uric acid nephropathy. However, it does not address existing uric acid crystals in the kidneys.
  • Rasburicase: A more effective option in acute TLS, rasburicase is an enzyme that converts uric acid into a more easily excretable compound, allantoin. It is particularly helpful in patients with very high uric acid levels.
  • Loop Diuretics (e.g., furosemide): After hydration, diuretics may be used to promote urine output and prevent fluid overload or worsening of kidney function.
  • Calcium Gluconate: If hypocalcemia is severe, calcium gluconate may be administered to stabilize the cardiac membrane and prevent arrhythmias.

3. Electrolyte Management:

  • Potassium and Phosphate: If hyperkalemia or hyperphosphatemia is severe, interventions such as calcium gluconate, insulin and glucose, or sodium bicarbonate may be used to temporarily reduce potassium levels. For phosphate, phosphate binders may be given.

4. Renal Support:

  • Dialysis may be required in cases where kidney function deteriorates rapidly or if conservative measures do not sufficiently manage electrolyte imbalances.

5. Monitoring:

  • Continuous monitoring of renal function, electrolytes, and vital signs is crucial, especially in the first 24-48 hours after initiating treatment, as TLS often manifests acutely.

Prevention of Tumour Lysis Syndrome

Preventing TLS is often more effective than treating it once it occurs, especially for patients at high risk. Key prevention strategies include:

  • Prophylactic Hydration: Administering IV fluids before starting cancer treatment can help prevent dehydration and the buildup of harmful substances.
  • Allopurinol: Starting allopurinol before chemotherapy in high-risk patients to reduce uric acid levels.
  • Close Monitoring: Regular monitoring of blood tests, particularly for high-risk patients, allows for early detection and intervention.
  • Use of Rasburicase: In certain high-risk patients (e.g., those with high tumor burden or rapid tumor lysis), rasburicase may be given preemptively to prevent TLS.

Prognosis

The prognosis of TLS depends on how quickly it is recognized and treated. In many cases, with timely interventions such as hydration, medications, and renal support, TLS can be managed successfully. However, if left untreated or if the condition becomes severe, TLS can lead to life-threatening complications, including acute renal failure, cardiac arrhythmias, and death.

Conclusion

Tumour Lysis Syndrome is a potentially fatal complication that occurs after the rapid breakdown of tumor cells, often as a result of cancer treatment. Early recognition and management of TLS, including hydration, medications, and electrolyte monitoring, are essential for preventing severe complications. With appropriate care, the outcome for patients with TLS can be significantly improved, underscoring the importance of preventive measures in high-risk cancer patients.