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Tumor Lysis Syndrome - Causes, Symptoms, and Management

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Tumor lysis syndrome is a group of metabolic disturbances that can occur as a complication of cancer treatment. Read this article to know more about it.

Written by

Dr. Ramji. R. K

Medically reviewed by

Dr. Rajesh Gulati

Published At December 2, 2022
Reviewed AtMay 30, 2023

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.

Frequently Asked Questions

1.

What Are the Markers for Tumor Lysis Syndrome?

Hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia are the few metabolic derangements associated with tumor lysis syndrome. And there is also elevation in blood urea nitrogen (BUN), creatinine, and lactate dehydrogenase are also elevated in tumor lysis syndrome.

2.

What Treatment Is Advised for Tumor Lysis?

Usually, treatment of TLS includes intensive hydration, stimulation of diuresis, and most importantly the use of Allopurinol and Rasburicase. This drug Rasburicase is given as a single fixed dose (maximum 6 milligram) to treat tumor lysis syndrome in adults.

3.

How Can Individuals Prevent Tumor Lysis Syndrome?

The fundamental preventive measures taken for patients who are at risk of developing TLS are undergoing hydration, monitoring electrolyte imbalance, and hypouricemic therapy with Allopurinol and Rasburicase. The main cornerstone to prevent TLS will be intravenous hydration. Prevention is considered the most important component of treatment for TLS. Prevention is considered vital to treatment for TLS.

4.

Name the Risk Factors of Tumor Lysis Syndrome?

The risk of tumor lysis syndrome is increased through factors like LDH elevation, bone marrow involvement is more, pre-existing renal disease, urinary output is reduced, increase in age, and also drug usage increases the serum uric acid like alcohol, thiazide, diuretics, and levodopa.
If patients have rapidly dividing cells, like acute leukemia or high-grade lymphoma or tumors, they are at greater risk of developing TLS.

5.

Why Is Tumor Lysis Defined as an Emergency?

Generally, the most common oncological emergency is tumor lysis syndrome. Tumor lysis syndrome is defined as an oncological emergency. Because it is caused by a massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation. It usually occurs due to rapid cell destruction and due to results of nucleic acid degradation during or days after initiation of cytotoxic therapy. This can also exist as spontaneous forms.

6.

What Happens to an Individual When Tumor Lysis Occurs?

People can get tumor lysis syndrome only when the tumor cells release their contents into the bloodstream, through response to therapy or spontaneously leading to characteristic findings of hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia.

7.

Which One Is Defined as the Most Common Lab Abnormality Seen in Tumor Lysis Syndrome?

The most common lab abnormalities seen in tumor lysis syndrome patients are lactate dehydrogenase, potassium, phosphate, calcium, and uric acid, as well as some abnormal renal functions, which occur 1 to 3 days after chemotherapy initiation. Hyperkalemia is usually defined as a first life-threatening abnormality.

8.

Which Fluid Is Best for Tumor Lysis Syndrome?

The first line treatment for patients who are at high risk for clinical tumor lysis syndrome is Rasburicase. TLS patients should receive aggressive IV fluids with the goal of a urine output which can be at least 2 milliliter per kilogram per hour, unless they are anuric.

9.

How Is Tumor Lysis Syndrome Clinically Presented?

Tumor lysis syndrome is clinically presented by symptoms like nausea with or without vomiting, fatigue and lack of appetite, flank pain or reduced urine output and dark urine. Additionally, seizures. hallucinations and numbness is present.

10.

What Is the Reason for LDH Elevation in Tumor Lysis Syndrome?

Patients with TLS will particularly show an increase in the lactate dehydrogenase (LDH), because there is an occurrence of anaerobic glucose metabolism. However, in the laboratory definition of LDH, the elevation of LDH is not included in it. And it is important to note that LDH is very sensitive but it is defined as an nonspecific marker for TLS.

11.

Why Is Electrolyte Imbalance Seen in Tumor Lysis Syndrome?

Hyperphosphatemia is one of the electrolyte imbalances seen along with tumor lysis syndrome. A significant amount of phosphorus is released into the bloodstream when there is a breakdown of a tumorous cell present in the phosphate group of the nucleic acid. Usually most of the phosphorus is excreted through kidneys.

12.

Why Is There High Are Uric Acid Levels in TLS?

When the cancer cells break down rapidly in the body, the levels of uric acid, phosphorus, and potassium levels are raised. This process is faster than the kidney’s ability to remove it and leads to the formation of TLS. There levels of calcium in the blood of an individual also will be low because excess amounts of phosphorus is removed by the calcium.
Dr. Rajesh Gulati
Dr. Rajesh Gulati

Family Physician

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