Tumor Lysis Syndrome

Overview

Tumor lysis syndrome (TLS) is a potentially life-threatening medical emergency that occurs when large numbers of cancer cells die rapidly, releasing their contents into the bloodstream. This sudden release overwhelms the body’s ability to eliminate the cellular debris, leading to severe metabolic imbalances. TLS is most commonly associated with the treatment of high-grade hematologic malignancies, such as leukemia and lymphoma, particularly when they are highly sensitive to chemotherapy. However, TLS can also occur spontaneously, without treatment, in tumors with a high cell turnover. If not promptly recognized and managed, TLS can lead to acute kidney injury, cardiac arrhythmias, seizures, and death.

Causes

The underlying cause of tumor lysis syndrome is the rapid destruction of malignant cells, which releases intracellular ions and metabolic byproducts into the bloodstream. These include potassium, phosphate, and nucleic acids that are metabolized into uric acid. Key contributing factors include:

• Cancer types:

  • Acute lymphoblastic leukemia (ALL)

  • Acute myeloid leukemia (AML)

  • High-grade non-Hodgkin lymphomas, especially Burkitt lymphoma

• Cancer treatment:

  • Initiation of cytotoxic chemotherapy

  • Radiation therapy

  • Targeted therapies or immunotherapy (e.g., CAR-T cells)

• Spontaneous TLS: In rare cases, TLS can occur prior to treatment due to natural tumor breakdown.

• Risk factors:

  • Large tumor burden

  • High cell proliferation rate

  • High sensitivity to therapy

  • Pre-existing kidney dysfunction

  • Dehydration or hypotension

Symptoms

Symptoms of tumor lysis syndrome are due to the rapid metabolic disturbances caused by the release of intracellular contents. These symptoms may develop within 12 to 72 hours of starting cancer treatment or even occur spontaneously in rare cases. Common clinical features include:

Electrolyte and Metabolic Abnormalities:

• Hyperkalemia: Can cause muscle weakness, paresthesia, and life-threatening cardiac arrhythmias

• Hyperphosphatemia: Can lead to calcium-phosphate precipitation, causing tissue damage and renal dysfunction

• Hypocalcemia: Results from phosphate binding calcium; symptoms include muscle cramps, tetany, confusion, and seizures

• Hyperuricemia: Uric acid can precipitate in the renal tubules, causing acute kidney injury

Systemic Manifestations:

• Nausea and vomiting

• Diarrhea

• Lethargy or confusion

• Seizures

• Decreased urine output or dark-colored urine

• Cardiac arrhythmias or cardiac arrest

Diagnosis

Tumor lysis syndrome is diagnosed based on laboratory findings and clinical symptoms. The Cairo-Bishop criteria are commonly used to define laboratory and clinical TLS:

Laboratory TLS (two or more of the following within 3 days before or 7 days after cancer treatment):

• Uric acid > 8 mg/dL (or 25% increase)

• Potassium > 6.0 mEq/L (or 25% increase)

• Phosphorus > 4.5 mg/dL in adults (or 25% increase)

• Calcium < 7.0 mg/dL (or 25% decrease)

Clinical TLS (laboratory TLS plus one or more of the following):

• Increased serum creatinine (>1.5 times upper limit of normal)

• Cardiac arrhythmia or sudden death

• Seizure

Other diagnostic steps include:

• Electrocardiogram (ECG): To assess for arrhythmias related to electrolyte imbalances

• Renal function tests: Monitoring BUN and creatinine for signs of kidney injury

• Urinalysis: To evaluate uric acid crystals or signs of renal tubular obstruction

Treatment

The management of tumor lysis syndrome involves prevention, early recognition, and aggressive treatment of metabolic abnormalities. Key treatment strategies include:

1. Prevention (for high-risk patients):

• Aggressive hydration: Intravenous fluids started before chemotherapy to promote renal clearance of uric acid and electrolytes

• Allopurinol: Xanthine oxidase inhibitor that reduces the formation of uric acid

• Rasburicase: Enzyme that rapidly breaks down existing uric acid; used in high-risk or established TLS

• Monitoring: Frequent lab assessments (every 4–6 hours) of electrolytes, uric acid, and renal function

2. Treatment of Established TLS:

• Continued hydration: To maintain high urine output (2–3 liters/day)

• Electrolyte management:

  • Calcium gluconate for symptomatic hypocalcemia (with caution)

  • Insulin and glucose, sodium bicarbonate, or beta-agonists for hyperkalemia

  • Phosphate binders for hyperphosphatemia

• Dialysis: Required for severe renal failure, refractory hyperkalemia, or fluid overload

Prognosis

The prognosis of tumor lysis syndrome depends on the speed of diagnosis, severity of metabolic disturbances, and timeliness of treatment. Key considerations include:

• Excellent prognosis: In patients who receive preventive therapy and close monitoring, particularly in controlled hospital settings

• Increased morbidity and mortality: In cases of delayed recognition, especially in spontaneous TLS or when complicated by acute kidney injury and cardiac events

• Survivability: With early and aggressive management, most patients recover fully from the metabolic complications

• Long-term outcomes: Dependent on the underlying malignancy and overall treatment response

Proactive identification and management of high-risk patients remain the cornerstone of improving outcomes in tumor lysis syndrome.