What Is Tumour Lysis Syndrome?

Defining tumour lysis syndrome 

Tumour lysis syndrome (TLS) refers to a condition experienced when tumour cells release their contents into the bloodstream. With ‘lysis’ referring to the breakdown and rupture of a cell’s wall or membrane, tumour lysis syndrome refers specifically to the breakdown of these structures in tumour cells. This breakdown of tumour cell structure can be either spontaneous or induced by targeted therapy for cancer. Considered an oncological (cancer-related) emergency,¹ tumour lysis syndrome requires prompt diagnosis and urgent treatment due to it giving rise to serious kidney, heart, and neurological complications if left untreated.² 

What happens in tumour lysis syndrome? 

There are two distinct causes of tumour lysis syndrome: spontaneous lysis or therapy-induced lysis.¹ As tumour cells are highly proliferative (i.e. they rapidly divide and multiply in number), they are known to have a high ‘turn-over rate’. This essentially means that new cells are rapidly made to replace the older tumour cells, thereby ensuring a continuous and exponentially growing population of ‘newer’ tumour cells. This rapid ‘turn-over’ often brings with it the destruction and elimination of the older cells, thereby releasing the contents of these cells into the bloodstream. It is through these mechanisms that spontaneous tumour lysis syndrome is observed. 

Tumour lysis syndrome is most often seen in patients diagnosed with cancer who are receiving targeted therapies such as chemotherapy. As these therapies specifically target tumour cells, tumour lysis syndrome develops most commonly in the 48-72 hours (2-3 days) after the initiation of therapy.³ Targeting large numbers of tumour cells at once, the attack on these clusters of cells results in the release of a large amount of intracellular contents into the patient’s blood within a short space of time.²

This destruction and breakdown of tumour cells causes potassium, phosphorus, and nucleic acids (stores of genetic information) to be released into the blood.¹ Importantly, nucleic acids are metabolised by the body to uric acid¹ and it is this substance, alongside potassium and phosphorus, which requires excretion from the body. These higher-than-normal concentrations of substances in the blood can lead to the dysfunction of several important organs. 

As the body is now tasked with removing large quantities of substances from the bloodstream, the kidneys are the organs that most commonly incur severe damage in tumour lysis syndrome. Furthermore, the sensitivity of the heart and brain to these substances can also lead to severe, and sometimes fatal, complications.¹ Such symptoms and complications will be covered in the latter part of this article. 

Risk factors predisposing patients to the development of tumour lysis syndrome 

Whilst tumour lysis syndrome can occur in all types of cancer, patients diagnosed with acute leukaemias and non-Hodgkin lymphomas (such as Burkitt lymphoma) are the most predisposed to developing tumour lysis syndrome.  High incidences of tumour lysis have also been reported in those with blood-related cancers and other tumours such as hepatoblastoma (liver cancer) and neuroblastoma (a rare type of cancer that develops in nerve tissue).^2,3 Other associated risk factors that can further enhance the risk of developing tumour lysis syndrome are: 

• Bulky tumours (large tumours above a certain size)
• Rapidly proliferating tumours (tumours that grow and multiply rapidly)
• Tumours that are sensitive to therapy
• High white cell count 
• High blood uric acid concentrations 
• Kidney problems 
• Dehydration¹

Clinical presentations and symptoms of tumour lysis syndrome 

As discussed earlier, the lysis (i.e. the breakdown) of tumour cells releases a large amount of intracellular substances into the bloodstream. This results in high concentrations of uric acid, potassium, and phosphate in the blood.¹ The majority of symptoms associated with tumour lysis syndrome relate to the disruption caused by these substances.² Clinically, tumour lysis syndrome is characterised by the development of hyperuricemia, hyperkalemia, and hyperphosphatemia.³

Hyperuricemia (high uric acid level)

Uric acid is a normal ‘waste product’ of human metabolism, which is processed and removed from the body by our kidneys. Hyperuricemia is a condition that develops when too much uric acid remains in the body. This can cause severe kidney damage in those suffering from tumour lysis syndrome. 

High levels of uric acid can accumulate and ‘crystalise’ within the kidneys, leading to acute kidney injury^.1 Patients with hyperuricemia-associated acute kidney injury may notice symptoms such as blood in their urine, pain upon urination, or the inability to urinate. Other symptoms associated with hyperuricemia include: 

• Fatigue 
• Muscle weakness
• Nausea and vomiting 
• Restless legs 
• Metallic taste in the mouth 
• Itchy skin

Hyperkalaemia (high potassium level)

Due to the large amounts of potassium released upon lysis of the cells and impaired excretion of this due to kidney damage, potassium raises to dangerous levels within the blood. This condition is called hyperkalaemia, the symptoms of which include: 

• Heart palpitations 
• Shortness of breath 
• Chest pain 
• Nausea and vomiting 
• Life-threatening cardiac arrhythmias

Hyperphosphatemia (high phosphate level) 

Hyperphosphatemia is a condition in which there is too much phosphate in the blood. High levels of phosphate within the bloodstream do not tend to induce any immediate symptoms of their own. However, high phosphate can often cause rapid depletion of a person’s calcium levels, leading to the following symptoms: 

• Muscle cramps 
• Paraesthesia (tingling) around the lips, tongue, fingers and/or feet
• Issues with memory 
• Arrhythmias (irregular heartbeat)
• Hair that feels more coarse and brittle than is normal  
• Dry skin⁶ 

Diagnosing tumour lysis syndrome

If a doctor suspects you have tumour lysis syndrome, they will first ask you a series of questions pertaining to the symptoms outlined above. Following these questions, the doctor may then order a series of tests to confirm their diagnostic suspicions. Such tests include laboratory tests, kidney function tests, and diagnostic imaging. 

Laboratory tests 

Doctors will order tests to investigate the serum concentrations of uric acid, potassium, phosphate, and calcium.² Serum concentration refers to the concentration of something within your blood.

When looking at these results, doctors will compare these concentrations with the normal concentrations typically found in healthy individuals. If these concentrations are higher for uric acid, potassium, and phosphate with an accompanying lowered calcium, tumour lysis syndrome can be diagnosed. 

Kidney function tests 

To assess for kidney damage that is typically associated with tumour lysis syndrome, doctors will measure serum creatinine. Creatinine is a natural waste-product of the body’s metabolism and so if kidney function is impaired, creatinine will be present in higher concentrations within the blood. 

If this value is raised 1.5x above the normal values, doctors may diagnose tumour lysis syndrome associated acute kidney Injury.

Imaging

Doctors may use imaging tests such as an X-ray or CT scan to assess the tumour for signs of tumour lysis syndrome.² Doctors may also make use of dye to further assess any damage or changes to the tumour.² 

Tests to assess complications

Tests to assess complications associated with tumour lysis syndrome may include:

• Electrocardiogram (ECG) to assess any heart complications associated with tumour lysis syndrome
• Full blood count to assess changes to the tumour by assessment of concentrations of substances within the bloodstream
• Urine analysis to assess the concentrations of uric acid in the blood ² 

How is tumour lysis syndrome treated? 

Treatment of tumour lysis syndrome is related mostly to the prompt and rapid correction of the high concentrations of intracellular contents within the blood. In the presence of tumour lysis syndrome, clinicians will follow the following steps: 

• Intravenous (IV) rehydration - Doctors will initiate patients with tumour lysis syndrome on an intravenous (IV) rehydration regime. This increases the volume of fluid in the blood and helps to dilute the concentrations of these substances in the blood whilst encouraging greater frequency and volume of urination to clear the substances from the body.²
• Diuretics - Diuretics may be used to encourage greater urination and clearance of these substances from the bloodstream.
• Medications used to lower high potassium - In patients with tumour lysis syndrome, doctors will act rapidly to correct the high levels of potassium in order to prevent the development of any fatal arrhythmias. Medications such as calcium gluconate may be used to protect the heart alongside a host of other drugs.¹
• Sodium bicarbonate - Doctors may also give IV sodium bicarbonate to further encourage the excretion of uric acid through urine.²
• Drugs to break down uric acid crystals in the kidneys - Drugs such as rasburicase and allopurinol are powerful medications used for the treatment of tumour lysis syndrome.^{2, 4} Rasburicase works by breaking down uric acid is also used in the prevention of tumour lysis syndrome.²
• Haemodialysis - In severe cases of tumour lysis syndrome, patients may be placed on haemodialysis to ensure the removal of excess substances.²

Summary 

Tumour lysis syndrome is a serious and life-threatening complication requiring urgent identification and treatment. Caused by the release of large levels of intracellular contents following the destruction of tumour cells, those suffering from tumour lysis syndrome can sometimes suffer from life-threatening complications such as cardiac arrhythmias and seizures. Characterised by raised levels of uric acid, potassium and phosphate, patients will also have a lowered level of calcium in their blood. Common symptoms related to these altered levels include nausea and vomiting, muscle cramps and weakness. Doctors will often order a series of tests to confirm the diagnosis of tumour lysis syndrome before treating this condition with a wide array of medications and IV infusions.