Tumor Lysis Syndrome - Causes, Symptoms, and Management

What Is Tumor Lysis Syndrome or TLS?

Tumor lysis syndrome refers to a group of metabolic disorders that occur as a complication of cancer treatment. It most commonly develops in high-grade non-Hodgkin's lymphoma and acute leukemia patients. It generally occurs in cancer patients within a few hours to several days after receiving the initial chemotherapy (cancer treatment that uses drugs to kill cancer cells). After the chemotherapy dose, the cancer cells undergo cellular breakdown and release the tumor contents into the bloodstream. Mostly kidneys can filter out the substances released from tumor cells without any problem. But sometimes, the tumor cell breakdown occurs faster, and the kidneys fail to filter these contents from the body leading to tumor lysis syndrome.

Tumor lysis syndrome is a life-threatening condition that requires immediate treatment.

What Causes TLS?

Tumor lysis syndrome mainly develops in patients within hours after receiving chemotherapy. Other than chemotherapy, tumor lysis syndrome is linked to;

• Radiation therapy may rarely lead to tumor lysis syndrome. In addition, reports show that radiation therapy for spleen and blood-related malignancies is mostly related to the development of tumor lysis syndrome.

• Corticosteroid therapy that is used in the management of blood-related cancer has induced tumor lysis syndrome.

• Immunotherapy drugs such as Pembrolizumab, Axitinib, etc., are linked to the increased incidence of tumor lysis syndrome.

However, some of the risk factors that increase the risk of developing tumor lysis syndrome include;

• Kidney problems.

• Dehydration.

• Large tumors.

• High white blood cell count.

• Elevated blood uric acid level.

Tumor lysis syndrome can also occur spontaneously, but it is rare. Spontaneous tumor lysis syndrome occurs due to the breakdown of tumor cells without chemotherapy.

What Are the Different Cancers That Increase the Risk of Tumor Lysis Syndrome?

Tumor lysis syndrome most likely develops in a person during the treatment of certain cancers such as;

• Non-Hodgkin's Lymphoma: Cancer that arises in the lymphatic system.

• Acute Leukemia: A type of blood cancer that develops in blood and bone marrow cells.

• Neuroblastoma: Cancer that develops in the nerve tissue.

• Breast Cancer: Cancer that develops in the breast cells.

What Are the Different Conditions Caused by Tumor Lysis Syndrome?

Tumor lysis syndrome is a group of metabolic conditions affecting muscles, kidneys, and the heart. Those conditions include the following;

• Hyperuricemia: Hyperuricemia refers to high uric acid levels in the blood (more than 7 mg/dl of uric acid in the blood). It affects kidney function by depositing uric acid crystals in the kidneys.

• Hyperphosphatemia: Hyperphosphatemia refers to high phosphate levels (more than 4.5 mg/dl of phosphate in the blood). It affects normal kidney function.

• Hyperkalemia: Hyperkalemia is a metabolic disorder characterized by high potassium levels in the blood. It affects normal heart rate leading to cardiac dysrhythmia (irregular heartbeat) and heart attacks.

• Hypocalcemia: Hypocalcemia refers to low levels of calcium in the blood. It occurs mainly due to hyperphosphatemia with the precipitation of calcium phosphate in the tissues.

• Uremia: Uremia refers to the high levels of urea in the blood. It occurs when kidneys fail to filter toxins from the blood. It may lead to severe issues in the heart, blood vessels, and bones.

What Are the Symptoms of Tumor Lysis Syndrome?

The symptoms of tumor lysis syndrome depend on specific conditions associated with it. Some of the common symptoms of tumor lysis syndrome include;

• Nausea and vomiting.

• Diarrhea.

• Fatigue.

• Loss of appetite.

• Muscle spasms.

• Joint pain.

• Cardiac dysrhythmia - When the heartbeat is irregular, with more than 100 beats or less than 60 beats in a minute, it is referred to as cardiac dysrhythmia.

• Hematuria (presence of blood in urine).

• Seizures.

• Decreased urination.

How Is Tumor Lysis Syndrome Diagnosed?

The doctors suggest blood tests for diagnosing tumor lysis syndrome. The blood tests look for any change in the levels of chemicals in the blood. The blood test may look at the levels of;

• Serum creatinine.

• Sodium.

• Potassium.

• Calcium.

• Phosphorous.

• Uric acid.

• Blood urea nitrogen.

• Lactate dehydrogenase.

• Serum electrolytes.

The doctor may also suggest urine tests to check for signs that the kidneys are filtering out everything effectively. Doctors generally use two sets of criteria for diagnosing tumor lysis syndrome. It includes;

Cairo-Bishop Criteria:

Cairo-Bishop criteria classified tumor lysis syndrome into two varieties;

1. Laboratory Tumor Lysis Syndrome: Laboratory tumor lysis syndrome is known as the abnormality in two or more of the following chemical levels that occurs within three to seven days after chemotherapy.

• Uric acid levels greater than 8 mg/dl or 25 % increase from baseline.

• Potassium levels greater than 6 meq/l or 25 % increase from baseline.

• Phosphate levels greater than 4.5 mg/dl or 25 % increase from baseline.

• Calcium levels lesser than 7 mg/dl or 25 % decrease from baseline.

2. Clinical Tumor Lysis Syndrome: Clinical tumor lysis syndrome is defined as the sum of laboratory tumor lysis syndrome with any one or more of the following symptoms;

• Increased serum creatinine (more than 1.5 times the normal limit).

• Seizures.

• Cardiac arrhythmias.

• Sudden death.

• Howard Criteria: Howard criteria were proposed by Howard in 2011, in which he refined the standard Cairo-Bishop criteria for tumor lysis syndrome. The Howard criteria refined the following two limitations of the Cairo-Bishop criteria;

• The 25 % change from baseline should be avoided as a criterion since such changes are not more clinically important unless the value exceeds the normal range.

• Two or more serum electrolytes should be outside the normal range.

It also suggests that only symptomatic hypocalcemia should constitute clinical tumor lysis syndrome.

How Is Tumor Lysis Syndrome Treated?

The treatment options depend on the specific metabolic disorders caused by tumor lysis syndrome. Some of the standard treatment options for tumor lysis syndrome include;

• To control hyperuricemia, doctors might suggest Allopurinol (a xanthine oxidase inhibitor), which prevents the body from making uric acid. Rasburicase (recombinant urate oxidase) is used when standard approaches cannot lower hyperuricemia. It has a more rapid action than Allopurinol.

• To treat hyperkalemia, doctors might suggest IV (intravenous fluids) to remove extra potassium and reduce dietary potassium. For mild hyperkalemia cases, a loop diuretic such as Furosemide or Bumetanide is given IV, calcium gluconate is used for cardioprotection when potassium levels are greater than 6.5 mmol/L.

• Oral phosphate binders (medications that reduce dietary phosphate absorption) help manage hyperphosphatemia. Low calcium levels in hypocalcemia are corrected by administering calcitriol.

• Dialysis is carried out in patients if the therapies mentioned above for tumor lysis syndrome fail. It helps remove unwanted toxins and waste products from the blood when kidneys fail to filter the blood. It is indicated in hyperphosphatemia, persistent hyperkalemia, uremia, hyperuricemia, and symptomatic hypocalcemia.

How Can Tumor Lysis Syndrome Be Prevented?

Tumor lysis syndrome can be prevented by undertaking the following measures;

• Monitor fluid balance in the body and vigorously hydrate patients with IV fluids before chemotherapy.

• Closely monitoring the potassium, calcium, and phosphorus levels to look for any abnormality in their levels.

• Allopurinol is given to inhibit uric acid production.

• Administration of diuretics to improve urine output.

Conclusion:

Tumor lysis syndrome is potentially a life-threatening condition requiring immediate treatment. Therefore, healthcare providers usually carry out preventive measures for people who are at increased risk of developing tumor lysis syndrome. The treatment options for tumor lysis syndrome mainly depend on the specific metabolic conditions that are associated with it. The main goal of treatment is to relieve the symptoms caused by different metabolic disorders of tumor lysis syndrome and improve the patient's overall health. Acute kidney failure is the leading cause of death in tumor lysis syndrome.