Tumor Lysis Syndrome: Symptoms, Causes, Treatment, Prognosis, Risk Factors, Epidemiology

There is a high proliferative rate for those, who have had tumors with large mass and those, who are highly sensitive to cytotoxic agents, to suffer from a constellation of metabolic disturbances. This is known as the Tumor Lysis Syndrome or TLS and it occurs when the therapy for the tumor or the cancer initiates. The result of this cancer treatment is associated with release of metabolic products of proteins and nucleic acids and rapid intracellular cations as well as anions, into bloodstream. Tumor Lysis Syndrome occurs mostly in those, who have rapidly proliferating, bulky and treatment-responsive tumors. The clinical spectrum that is associated with Tumor Lysis Syndrome or TLS is caused by the overwhelmed homeostatic mechanism of the body.

A tumor is an abnormal growth of tissue resulting from uncontrolled and progressive multiplication of cells which has no function. Lysis is the process of destruction that dissolute the body cells through the action of certain antibodies or lysins. The lysin is the antibody that disrupts the cell membrane. The syndrome on the other hand is a cluster of disorders.

Tumor Lysis Syndrome or TLS is a metabolic disturbance in the body that takes place, when the contents of the tumor cells get released to the bloodstream. The release of these tumor contents can be a result of a spontaneous exposure of the tumor cells or a response of the therapy.

In Tumor Lysis Syndrome, the clinical spectrum of the condition is associated with the body’s process to excrete the excessive amounts of uric acid, potassium, phosphates and urea that gets concentrated in the body due to cancer therapies and overwhelms the body’s homeostatic mechanisms. Those, who are already diagnosed with hematologic cancers that are the cancers related with bone marrow and blood stream, are often found to have this syndrome.

Since Tumor Lysis Syndrome or TLS is a constellation of metabolic disturbances, there are different kinds of difficulties that are associated with specific medical abnormalities. These are –

• Hyperuricemia- Dissimilation of nucleic acids and uric acids that are precipitated in the renal tubes. This leads to kidney failure.
• Hyperkalemia- Increased precipitation of potassium. This causes neuromuscular dysfunction and irregular cardiac rhythms.
• Hyperphosphatemia- Increased deposition of calcium phosphate in the renal tubes, leading to possible kidney failure.
• Hypocalcemia- Decreased deposition of calcium. This may result in severe neurological dysfunction, cardiovascular effects, problems related to bone health, etc.

There can be different signs and symptoms associated with Tumor Lysis Syndrome and most of them are specific depending on the specific medical abnormality or type of difficulty that has occurred. At the very beginning of Tumor Lysis Syndrome, the symptoms can be quite mild. But as the condition gets worse, the symptoms become stronger because of the increase of the abnormal substances in bloodstream. These symptoms include –

• Nausea and vomiting
• muscle cramps or twitches
• numbness or a tingling sensation
• decreased urination
• restlessness and irritability
• seizures
• delirium
• confusion
• hallucinations
• weakness
• irregular heart rate
• diarrhea
• fatigue

Tumor lysis syndrome is an oncologic emergency, a group of disorders that are characterized by severe electrolyte abnormalities and other medical conditions. Patients with lymphoproliferative malignancies are mostly seen to suffer from Tumor Lysis Syndrome since an imbalance of abnormal substances occurs in the blood as an after effect of the malignancy. Not only this, but those, who are undergoing treatments or for those, the treatment procedure has just initiated, Tumor Lysis Syndrome is a possibility. In simple words, when the tumors are treated by rapidly destroying them, the cells of these tumors and the contents within the tumor get into the bloodstream and cause Tumor Lysis Syndrome.

The different kinds of malignant as well as benign, yet solid tumors that can cause Tumor Lysis Syndrome are –

• Acute Leukemia
• Myeloproliferative Disorders
• Aggressive Non-Hodgkin Lymphoma
• Cancers That Cause Kidney Failure or Poor Kidney Function
• Solid tumors Like Stage IV Neuroblastoma And Hepatoblastoma

In each of these conditions, the white blood cell count rapidly increases. Even the tumors also have a high amount of tumor burden and abnormal substances that can cause the metabolic imbalance in cells, leading to Tumor Lysis Syndrome. Chemotherapy is also a major cause of this condition that can make Tumor Lysis Syndrome occur within a few hours of the initiation of the treatment or even after 48 to 72 hours. Not only chemotherapy, but radiation therapy, hormonal therapy, corticosteroids and biological therapy are also possible causes of Tumor Lysis Syndrome.

There are a few intrinsic tumor-related factors that clearly show the high possibility of an increased risk for developing tumor lysis syndrome. The most common and predominant risk factors amongst them are –

• Large tumor burden or the weight of the tumor, the larger is the tumor, the higher is the chance of Tumor Lysis Syndrome.
• High tumor cell proliferation rate
• Rapid cell turnover of high grade tumor
• Increased level of lactate dehydrogenase
• Sensitivity of the tumor to the chemotherapy or its drugs
• Poor kidney function
• High blood pressure
• Increased age

Although Tumor Lysis Syndrome can occur as an after effect of tumor or cancer treatments, there are a few kinds of diseases, rather cancer types, for which the chance of developing Tumor Lysis Syndrome is higher. These include ALL or acute lymphoblastic leukaemia, Burkitt’s lymphoma, AML or acute myeloid leukaemia and also melanoma.

Clinical evidences have shown that 3 to 7% of acute leukaemia cases have developed Tumor Lysis Syndrome, whereas 4 to 11% of the lymphoma cases have been seen to develop this condition, after the tumors and their treatments have started. These statistics are associated only with those cases, in which the Tumor Lysis Syndrome has been clinically significant. The laboratory occurrence of Tumor Lysis Syndrome for intermediate-grade or high-grade non-Hodgkin lymphomas has been 42% and for acute leukaemia is 70%. There can be significant rise in the frequency of occurrence of this condition in cancer patients or tumor patients, since high-dose regimens of treatment are becoming more common in practice. The effects or impacts of Tumor Lysis Syndrome can be seriously life threatening, but with proper identification of the condition or with proper preventive measures, it can well be managed.

Usually Tumor Lysis Syndrome or TLS is diagnosed by these following tests –

• Complete blood count
• Urinalysis
• Blood chemistry and uric acid levels in the blood

Since, rasburicase is present in the blood of the patient that acts as an ex vivo to convert uric acid to allantoin, it is very important that prompt blood tests are done in the laboratory as soon as the blood sample reaches the lab. If prompt tests are not done, it will yield false-low test results. A pre-chilled blood tube containing heparin should be used to collect the blood sample and the specimen should be immersed in an ice-water bath. Within 4 hours of the sample collection, the test must be done.

For those patients, who are already diagnosed with Tumor Lysis Syndrome and undergoing treatment with rasburicase dosage, the blood must be drawn or collected after 4 hours of the dosage of rasburicase. The process of collecting blood and testing it should be continued for every 6 to 8 hours, until Tumor Lysis Syndrome is found to be completely treated. Tests such as levels of calcium, electrolytes, phosphorus, renal function tests, and LDH are also done for testing Tumor Lysis Syndrome.

Two ways of treating Tumor Lysis Syndrome are common and effective and they are –

1. Medication to Treat Tumor Lysis Syndrome – In this process, Allopurinol (Zyloprim) is given to stop the body from making uric acid. Along with this, Rasburicase (Fasturtec) is given to breaks down the already formed uric acid so that the body can get rid of it. Sometimes, sodium bicarbonate or acetazolamide (Diamox) is given along with the intravenous fluids, so that the uric acids are not crystallized and the body can easily get rid of them. This is not recommended if the patient is already on a Rasburicase medication.
2. Dialysis – If kidney failure occurs, then this is the only way through which the wastes can be removed from the body.

Cancer patients, who are about to receive chemotherapy treatment and have cancerous tumor with a high cell proliferation rate and turnover rate, must be given prophylactic oral or IV Allopurinol or Axanthine oxidase inhibitor in order to prevent uric acid production. Adequate IV hydration must also be given in order to maintain high urine output that is more than 2.5 litres a day. To make sure that the electrolyte balance is not disrupted, potassium and other electrolytes are not added to the IV fluid. Symptoms of peripheral oedema, weight gain, neck vein distension and pulmonary crackles as well as dehydration symptoms such as dry skin, dry mucous membranes, weight loss, and thirst should be regularly monitored.

Tumor Lysis Syndrome or TLS is a common phenomenon that can occur in patients with tumor and malignant cells. The condition can be life-threatening and hence, it is very important that one undergoes regular checkups so that the condition can be prevented or diagnosed at an early stage.