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Tumor Lysis Syndrome: Causes, Symptoms & Treatment

Tumor lysis syndrome is a life-threatening metabolic complication of cancer treatment, caused by the rapid release of intracellular contents from dying tumor cells.

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Things worth knowing about "Tumor Lysis Syndrome"

Tumor lysis syndrome is a life-threatening metabolic complication of cancer treatment, caused by the rapid release of intracellular contents from dying tumor cells.

What Is Tumor Lysis Syndrome?

Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic emergency that occurs when large numbers of cancer cells are rapidly destroyed, releasing their intracellular contents into the bloodstream. This leads to dangerous elevations in potassium, phosphate, and uric acid, as well as a drop in calcium levels. These imbalances can cause severe organ damage, particularly to the kidneys, heart, and nervous system. TLS most commonly occurs as a complication of chemotherapy, immunotherapy, or radiation therapy, but may also arise spontaneously in rare cases.

Causes

TLS results from the massive breakdown of cancer cells. The most common triggers include:

Chemotherapy: The most frequently associated cause, especially in aggressive hematologic malignancies.
Immunotherapy and targeted therapy: Newer treatment modalities that can also provoke rapid tumor cell death.
Radiation therapy: Particularly in tumors with high radiosensitivity.
Spontaneous TLS: Rare, but possible in fast-growing tumors with a high rate of spontaneous cell death.

Patients at the highest risk include those with non-Hodgkin lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and other malignancies with a large tumor burden and high proliferation rate.

Symptoms

The symptoms of tumor lysis syndrome reflect the underlying electrolyte and metabolic disturbances:

Hyperkalemia (elevated potassium): Cardiac arrhythmias, muscle weakness, paralysis
Hyperphosphatemia (elevated phosphate): Renal impairment, calcium precipitation in tissues
Hypocalcemia (low calcium): Muscle cramps, tetany, cardiac arrhythmias
Hyperuricemia (elevated uric acid): Kidney stones, acute renal failure
Acute kidney injury: Due to uric acid and calcium phosphate crystal deposits in the renal tubules
General symptoms: nausea, vomiting, fatigue, altered consciousness, and seizures

Diagnosis

TLS is diagnosed using clinical and laboratory criteria. The widely used Cairo-Bishop classification distinguishes between laboratory TLS and clinical TLS:

Laboratory TLS: At least two of the following abnormalities within 3 days before to 7 days after the start of therapy: hyperuricemia, hyperkalemia, hyperphosphatemia, or hypocalcemia.
Clinical TLS: Laboratory TLS plus at least one clinical complication such as renal failure, cardiac arrhythmia, seizure, or death.

Diagnostic workup includes frequent blood tests to monitor electrolytes, uric acid, creatinine, and urea, as well as ECG monitoring for cardiac rhythm assessment.

Treatment

Management of TLS includes both preventive and therapeutic interventions:

Prevention

Hyperhydration: Aggressive intravenous fluid administration to promote renal excretion of uric acid and phosphate.
Allopurinol: Inhibits uric acid production; used prophylactically in patients at intermediate risk.
Rasburicase: An enzyme that directly degrades uric acid; recommended for high-risk patients or established TLS.
Close laboratory and vital sign monitoring before and during cancer therapy.

Therapeutic Interventions

Treatment of hyperkalemia: Sodium bicarbonate, calcium gluconate, insulin/glucose infusion, dialysis in severe cases.
Treatment of hyperphosphatemia: Phosphate binders, dialysis.
Treatment of hypocalcemia: Calcium gluconate in symptomatic patients.
Hemodialysis: For severe acute kidney injury or uncontrollable electrolyte disturbances.

Risk Stratification

Before initiating cancer therapy, patients are stratified into risk groups (low, intermediate, or high risk) to guide the intensity of prophylactic measures. Factors considered include tumor type, tumor burden, baseline renal function, and the planned treatment regimen.

References

Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. British Journal of Haematology. 2004;127(1):3-11.
Howard SC, Jones DP, Pui CH. The Tumor Lysis Syndrome. New England Journal of Medicine. 2011;364(19):1844-1854.
National Cancer Institute (NCI). Tumor Lysis Syndrome (PDQ) - Health Professional Version. U.S. National Institutes of Health, 2023.

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