Tumour Lysis Syndrome

Question 1

What is tumour lysis syndrome (TLS)?

Answer 1

Tumour lysis syndrome (TLS) is caused by the rapid death of tumour cells by chemotherapy, leading to a massive release of intracellular contents.

Question 2

Which cancers treated with chemotherapy commonly lead to TLS?

Answer 2

Treatment of high-grade lymphomas and leukaemias.

Question 3

Briefly describe the pathophysiology of TLS

Answer 3

TLS occurs from the breakdown of the tumour cells and the subsequent release of chemicals from the cell.

It leads to a high potassium and high phosphate level in the presence of a low calcium.

It should be suspected in any patient presenting with an acute kidney injury in the presence of a high phosphate and high uric acid level.

Question 4

Briefly describe the Cairo-Bishop scoring system of TLS

Answer 4

Laboratory tumor lysis syndrome:

• Abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy.
  
  • Uric acid > 475umol/l or 25% increase
  • Potassium > 6 mmol/l or 25% increase
  • Phosphate > 1.125mmol/l or 25% increase
  • Calcium < 1.75mmol/l or 25% decrease

Question 5

How does TLS impact kidney function?

Answer 5

Large amounts of cellular byproducts in the bloodstream can impair renal function and cause AKI.

Question 6

What are the risk factors for TLS?

Answer 6

• Haematological malignancy
• Large tumour burden
• Chemosenstiive tumours
• Recent chemotherapy
• Pre-existing renal imapirment
• Dehydration
• Volume depletion
• Nephrotoxic medication

Question 7

What haematological maliginancies is TLS most common in?

Answer 7

TLS most commonly develops in highly proliferative haematological malignancies, particularly high-grade non-Hodgkin’s lymphoma, acute lymphocytic leukaemia and acute myeloid leukaemia.

Question 8

How long after chemotherapy does TLS occur?

Answer 8

TLS appears within 7 days following the initiation of intensive systemic chemotherapy.

Question 9

How does TLS present?

Answer 9

• Syncope, chest pain and dyspnoea
• Seizures
• Nausea and vomiting
• Oliguria, anuria and haematuria
• Anorexia
• Diarrhoea
• Muscle weakness
• Muscle cramps
• Lethargy
• Paraesthesia
• Lymphadenopathy
• Hypertenion/ hypotension

Question 10

What investigations should be ordered for TLS?

Answer 10

• Serum uric acid
• Serum phosphate
• Serum potassium
• Serum calcium
• FBC
• Lactate dehydrogenase
• Serum creatinine
• Serum urea
• Urine pH

Question 11

Clinically, how can TLS be diagnosed?

Answer 11

Clinical tumor lysis syndrome:

• Laboratory tumour lysis syndrome plus one or more of the following:
  
  • Increased serum creatinine (1.5 times upper limit of normal)
  • Cardiac arrhythmia or sudden death
  • Seizure

Question 12

How are the serum levels of phosphate, potassium, calcium and uric acid changed in TLS?

Answer 12

Phosphate= raised.

Potassium= raised.

Calcium= low.

Uric acid= raised.

Question 13

Briefly describe the management of TLS

Answer 13

Initial management is with correction of the electrolyte abnormalities and intravenous fluids.

Question 14

What is the most serious clinical manifestation of TLS?

How is this treated?

Answer 14

Cardiac arrhythmias are the most serious clinical manifestation of TLS.

Calcium gluconate can be used to treat cardiac arrhythmias.

Question 15

Why do seizures occur in TLS?

Answer 15

Seizures are usually secondary to hypocalcaemia.

Question 16

Why is intensive fluid resuscitation used to treat TLS?

Answer 16

Aggresive hydration improves intravascular volume and enhances renal blood flow. A high glomerular filtration rate helps eliminate potassium, uric acid and phosphase from the bloodstream.

Question 17

What is the role of rasburicase in treating TLS?

How does rasburicase work?

Answer 17

Rasburicase is used to manage hyperuricaemia in patients with established TLS.

Rasburicase is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water-soluble than uric acid and is, therefore, more easily excreted by the kidneys.

Question 18

Why should rasburicase and allopurinol not be given together for the treatment of TLS?

Answer 18

Rasburicase and allopurinol should not be given together in the management of tumour lysis syndrome as this reduces the effect of rasburicase.

Question 19

How can TLS be prevented in high risk patients?

Answer 19

Before the initiation of cancer treatemnts, patients can be given either IV allopurinol or IV rasburicase.