Tumor Lysis Syndrome

What is Tumor Lysis Syndrome?

Tumor lysis syndrome is a collection of metabolic abnormalities due to the tumor cell lysis in patients with treatment for malignancies.

Treatment of the cancer causes lysis of tumor cells which results in the release of the intracellular contents like electrolytes, nucleic acids and proteins. It leads to an increase in the levels of potassium, phosphate, uric acid and decrease in the calcium levels in the blood.

What are the Risk factors for Tumor Lysis Syndrome?

Tumor lysis syndrome is a complication in patients with treatment for cancer. The manifestation of the tumor lysis syndrome depends on various factors like the size of the tumor, the potential for tumor cell lysis, tumor chemosensitivity, supportive care and the patient health condition.

The cancers where the potential for cell lysis is more are

• High-grade lymphomas
• Acute leukemia

• Rapidly proliferating tumors

The patients with high risk to develop the tumor lysis syndrome are those with

• Pre-existing renal insufficiency
• Dehydration
• Oliguria
• Hypotension
• Acidic urine

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What are the Symptoms and Signs of Tumor Lysis Syndrome?

The signs and symptoms of tumor lysis syndrome are due to the release of intracellular contents.

• Hyperkalemia: It can cause cardiac arrhythmias and severe muscle weakness.
• Hyperphosphatemia: It causes renal failure due to deposition of calcium phosphate crystals.
• Hypocalcemia: Hypocalcemia can manifest with tetany, myopathy, dysrhythmias and seizures.
• Hyperuricemia: The cell lysis causes the release of the nucleic acids which are later converted to uric acid. The uric acid can cause acute renal failure due to acute uric acid nephropathy.
• Cytokines: The cytokines released during tumor lysis cause systemic inflammatory response syndrome and multi-organ failure.

How do you Diagnose Tumor Lysis Syndrome?

Acute renal failure with increased serum uric acid and phosphorus in patients with cancer treatment suggests tumor lysis syndrome. Tumor lysis syndrome is classified based on laboratory findings and its clinical presentation.

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Cairo-Bishop definition

Laboratory tumor lysis syndrome:

• Uric acid greater than 8mg/dl or 25% increase
• Potassium greater than 6meq/l or 25% increase
• Phosphate greater than 4.5mg/dl or 25% increase
• Calcium less than 7mg/dl or 25% decrease

Clinical tumor lysis syndrome:

• Creatinine greater than 1.5 times normal
• Cardiac arrhythmia/sudden death
• Seizure

Howard Definition

This is a refinement of the standard Cairo-Bishop definition of TLS accounting for 2 limitations.

Two or more electrolyte abnormalities should be present at the same time so as to confirm that the variations are solely due to TLS.

The 25% change from baseline should not be considered as a criterion.

What is the Treatment for Tumor Lysis Syndrome?

Recognizing the patients at risk of developing tumor lysis syndrome is important because it helps to take precautions before initiating the chemotherapy. Management of the tumor lysis syndrome includes preservation of renal function, prevention of arrhythmias and neuromuscular irritability. Early management of the tumor lysis syndrome is essential since the delay in the treatment can lead to the development of life-threatening complications.

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Monitoring the blood levels of creatinine, potassium, uric acid, phosphorus, calcium, uric acid, sodium and LDH before and after the cancer therapy is essential. Monitoring the EKGs and heart during the therapy is essential. Adequate intravenous hydration for 1-2 days before the initiation of the therapy is important.

Fluids and Hydration: Adequate hydration is necessary to prevent and treat tumor lysis syndrome. The amount of IV fluids to hydrate is about 3L/m²/day.

Allopurinol: It is a hypouricemic agent which decreases the conversion of nucleic to uric acid. It should be given even before the initiation of the therapy.

Rasburicase: It promotes the degradation of the uric acid. It converts the uric acid to allantoin thereby decreasing the uric acid levels.

Renal Replacement Therapy: Dialysis is necessary for patients with acute kidney injury, severe electrolyte abnormalities and uremia due to tumor lysis syndrome.

Hypocalcemia: Administration of intravenous calcium gluconate if there is a significant decrease in calcium.