An Overview of Tumor Lysis Syndrome

The Most Common Cancer Emergency

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Table of Contents

Tumor lysis syndrome (TLS) occurs when a massive number of cancer cells die and release various electrolytes, proteins, and acids into a patient's bloodstream. The massive and sudden cell death most commonly occurs after a person with blood cancer (usually acute leukemia or an aggressive lymphoma, such as Burkitt lymphoma) receives chemotherapy to kill cancer cells.

As a result of this large spill of cell contents (potassium, phosphate, and uric acid) into the bloodstream, various symptoms may develop, such as nausea, vomiting, kidney failure, and heart arrhythmias.

The diagnosis of tumor lysis syndrome is made by assessing the person's symptoms and evaluating laboratory tests for the presence of metabolic abnormalities (such as high potassium or uric acid levels in the bloodstream).

Emergency treatment of tumor lysis syndrome is essential, considering some of the symptoms are potentially life-threatening. Therapies include vigorous hydration, correction of electrolyte abnormalities, and sometimes dialysis.

Symptoms

The sudden release of cancer cells' inner contents is what ultimately causes the various symptoms and signs seen in tumor lysis syndrome.

These may include:

Acute kidney failure (as evidenced by a person who has an increased creatinine level and low or no urine output) is another major potential consequence of TLS. In fact, research has found that acute kidney injury that develops from TLS is a strong predictor of death.

The symptoms of TLS usually occur within seven days of a person undergoing cancer treatment (e.g., chemotherapy).

Causes

Tumor lysis syndrome can develop when there is a large number of cancer cells that die suddenly. As tumor cells "lyse" or die and rapidly break open, their spilled contents—potassium, phosphate, and uric acid—are released in large amounts into the patient's bloodstream.

This spillage ultimately leads to the following metabolic abnormalities:

  • High blood levels of potassium (hyperkalemia)
  • High blood levels of phosphate (hyperphosphatemia)
  • High blood levels of uric acid (hyperuricemia)

In addition to the above abnormalities, the extra phosphate present in the bloodstream may bind to calcium to form calcium phosphate crystals. Besides causing low blood levels of calcium (hypocalcemia), these crystals can deposit themselves in organs, like the kidney and heart, and cause damage.

In addition to electrolytes and acids, the death of tumor cells can lead to the release of proteins called cytokines. These cytokines may trigger a whole-body inflammatory response which can ultimately lead to multi-organ failure.

Risk Factors

While TLS most commonly develops after a patient receives chemotherapy, it can rarely occur spontaneously. This means that the cancer cells break open and spill their contents on their own, before even being exposed to one or more cancer drugs.

There are also reports of TLS developing after treatment with radiation, dexamethasone (a steroid), thalidomide, and various biologic therapies, such as Rituxan (rituximab).

The people most at risk for developing tumor lysis syndrome are those with blood cancers, especially acute lymphoblastic leukemia and high-grade lymphomas (such as Burkitt lymphoma). However, TLS can also occur, albeit rarely, in patients with solid tumors such as lung or breast cancer.

Research has found that more than 1 in 4 children with acute lymphoblastic leukemia will develop TLS after undergoing cancer treatment.

In general, there are tumor-specific factors that increase a person's risk of developing TLS. These factors include:

  • Tumors that are particularly sensitive to chemotherapy
  • Tumors that are growing fast
  • Bulky tumors (meaning the individual tumor masses are greater than 10 centimeters in diameter)
  • Large tumor burden (meaning there is a large amount of tumor throughout the body)

There are also patient-specific factors that make a person more prone to developing TLS. For example, patients who are dehydrated or have kidney failure are at an increased risk. This is because these conditions make it harder for their bodies to clear the cells' spilled contents.

Patients with high blood levels of phosphate, potassium, and uric acid prior to undergoing cancer treatment are also at an increased risk for developing TLS.

Diagnosis

Tumor lysis syndrome is suspected when a patient with acute leukemia, aggressive lymphoma, or otherwise large tumor burden develops acute kidney failure and various blood value abnormalities, such as high potassium or high phosphate levels, after undergoing treatment for their cancer.

To aid in the diagnosis, doctors often use the Cairo and Bishop classification system. This system classifies two types of tumor lysis syndrome—laboratory TLS and clinical TLS.

Laboratory TLS

Laboratory TLS means that two or more of the following metabolic abnormalities have occurred within three days before or seven days after the start of chemotherapy:

  • Hyperuricemia
  • Hyperkalemia
  • Hyperphosphatemia
  • Hypocalcemia

There are specific laboratory numbers that a doctor will look for when diagnosing TLS—for example, a uric acid level of 8 milligrams per deciliter (mg/dL) or more, or a calcium level of 7 mg/dL or less.

These abnormalities would be seen despite adequate hydration and the use of a hypouricemic agent (a drug that either breaks down uric acid or reduces the production of uric acid in the body).

Hydration and taking a hypouricemic agent are standard preventive therapies for TLS.

Clinical TLS

Clinical TLS is diagnosed when the laboratory criteria from above are met, plus at least one of the following clinical scenarios:

  • Abnormal heart rhythm or sudden death
  • A creatinine (a measurement of kidney function) level that is greater than or equal to 1.5 times the upper limit of normal for the patient's age
  • Seizure

Treatment

If a person is diagnosed with tumor lysis syndrome, they may be admitted to an intensive care unit (ICU) for continuous heart monitoring and care. In addition to the ICU specialist and the cancer care team, a kidney specialist (called a nephrologist) is usually consulted.

The treatment plan for TLS generally consists of the following therapies:

Vigorous Hydration and Monitoring Urine Output

The person with TLS will receive ample fluids through one or more intravenous (IV) lines with a goal of maintaining a urine output that is greater than 100 milliliters per hour (mL/h). A type of diuretic called Lasix (furosemide), may be given to help increase a person's urine output.

Correcting Electrolyte Abnormalities

The person's electrolytes will be monitored very carefully (every four to six hours, usually) and corrected as needed.

High potassium levels: To lower the potassium levels (which is critical as high levels can cause fatal heart arrhythmias), a doctor may administer one or more of the following therapies:

  • Kayexalate (sodium polystyrene sulfonate)
  • Intravenous (IV) insulin and glucose
  • Calcium gluconate
  • Albuterol
  • Dialysis (if severe or persistent)

High phosphate levels: Drugs called oral phosphate binders—such as PhosLo (calcium acetate)—are taken with meals to reduce the absorption of phosphorus into the gut.

High uric acid levels: A drug called Elitek (rasburicase), which triggers the degradation of uric acid in the body, is often given.

Rasburicase is contraindicated in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency because it may cause methemoglobinemia and hemolytic anemia. Those with this condition are given a different hypouricemic drug called Zyloprim (allopurinol).

Low calcium levels: Treatment for low calcium levels—giving calcium supplements—is only done if a patient is symptomatic (for example, experiencing seizures or heart arrhythmia).

Raising calcium levels increases the risk of calcium phosphate crystallization, which can damage organs (including the kidney and heart).

Dialysis

There are certain indications for dialysis in patients with tumor lysis syndrome.

Some of these indications include:

  • No or severely low urine output
  • Fluid overload (this can cause complications like pulmonary edema, where the heart and lungs are flooded with excess fluid)
  • Persistent hyperkalemia
  • Symptomatic hypocalcemia

Prevention

In people undergoing cancer therapy, several strategies may be implemented to prevent TLS from even occurring in the first place.

These strategies often include:

  • At least twice-daily drawing of blood tests (for example, a basic metabolic panel to check for high potassium levels and kidney dysfunction)
  • Vigorous fluid administration and close monitoring of urine output
  • Monitoring for heart arrhythmias
  • Limiting potassium and phosphorus dietary intake starting three days before and the seven days after starting cancer treatment

Lastly, medium to high-risk patients (such as a person with acute leukemia who has underlying kidney problems), will take a medication that preventively lowers uric acid levels in the body, such as allopurinol or rasburicase

A Word From Verywell

Tumor lysis syndrome is considered a cancer emergency because it is potentially fatal if not recognized and treated promptly. The good news is that most people who undergo chemotherapy do not develop TLS, and for those at an increased risk, doctors can be proactive and implement preventive strategies to minimize those chances.

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