Medicine chapters
Tumour lysis syndrome
An oncological emergency in which rapid death of cancer cells floods the blood with potassium, phosphate and urate, causing low calcium, arrhythmias and acute kidney injury.
- Rapid tumour cell death (usually after the first chemotherapy) releases potassium, phosphate and nucleic acids (→ urate); phosphate binds calcium, so calcium falls.
- Highest risk: Burkitt lymphoma, ALL, AML with a very high white count and other bulky, fast-growing, chemo-sensitive tumours, plus dehydration or renal impairment.
- Prevent with vigorous IV hydration and allopurinol (lower risk) or rasburicase (high risk, avoid in G6PD deficiency); treat hyperkalaemia urgently; dialysis if needed.
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Overview
Tumour lysis syndrome (TLS) happens when a large number of cancer cells die quickly and spill their contents into the blood. The kidneys cannot clear the load, so potassium, phosphate and uric acid rise and calcium falls.
It is an oncological emergency because of cardiac arrhythmias, seizures and acute kidney injury. It is mostly preventable if high-risk patients are recognised before treatment.
Definition
TLS is the metabolic result of rapid tumour breakdown:
- Laboratory TLS: the electrolyte changes (raised urate, potassium and phosphate; low calcium) around the start of treatment.
- Clinical TLS: laboratory TLS plus organ damage: acute kidney injury, arrhythmia or sudden death, or seizures.
Causes and risk factors
When it happens
- Usually within a few days of the first cycle of chemotherapy (sometimes after steroids or radiotherapy alone).
- Can occur spontaneously in very fast-growing tumours before any treatment.
Who is at risk
| Tumour factors | Patient factors |
|---|---|
| Burkitt lymphoma (classic) | Dehydration, low urine output |
| Acute lymphoblastic leukaemia | Pre-existing renal impairment |
| AML with a very high white count | High baseline urate or phosphate |
| Other high-grade lymphomas (e.g. DLBCL), bulky disease | Nephrotoxic drugs |
| High LDH (marker of tumour burden) | |
| Very chemo-sensitive tumours; rarely solid tumours (e.g. small cell lung cancer) |
The typical exam stem is a patient with Burkitt lymphoma or ALL who becomes oliguric with high potassium a day or two after starting chemotherapy.
Pathophysiology
| Released from dying cells | Consequence |
|---|---|
| Potassium | Hyperkalaemia → arrhythmias, cardiac arrest |
| Phosphate | Hyperphosphataemia → binds calcium → hypocalcaemia; calcium phosphate crystals in kidney |
| Nucleic acids (purines) → hypoxanthine → xanthine → uric acid (via xanthine oxidase) | Hyperuricaemia → urate crystals block renal tubules (acute urate nephropathy) |
| Low calcium | Tetany, cramps, seizures, arrhythmia, long QT |
- Urate can rise to several times the upper limit of normal.
- Kidney injury then worsens every other abnormality, because the kidney is the main route for clearing potassium, phosphate and urate.
"3 up, 1 down": potassium, phosphate and urate up; calcium down.
In TLS the calcium is low, not high. Hypercalcaemia in a cancer patient points to bone metastases, myeloma or PTHrP, not TLS.
Clinical features
- Nausea, vomiting, lethargy.
- Oliguria, fluid overload, rising creatinine.
- Muscle cramps, tetany, paraesthesia, seizures (low calcium).
- Palpitations, arrhythmia, cardiac arrest (high potassium, low calcium).
- Flank pain or haematuria from crystals.
Investigations
- Before and frequently after starting chemotherapy (often every few hours in high-risk patients): potassium, phosphate, calcium, urate, creatinine and urea, LDH.
- ECG and cardiac monitoring for hyperkalaemia (peaked T waves, wide QRS) and hypocalcaemia (long QT).
- Strict fluid balance and urine output.
Prevention
| Risk | Prevention |
|---|---|
| Low | Oral/IV fluids, monitoring; allopurinol may be used |
| Intermediate | IV hydration + allopurinol started before chemotherapy |
| High (e.g. Burkitt, ALL with high count, existing renal impairment) | Vigorous IV hydration + rasburicase; frequent monitoring; ICU/renal access |
Hydration is the cornerstone: keeping a high urine output washes out potassium, phosphate and urate. Diuretics may be used once the patient is well filled. Avoid potassium in IV fluids and avoid nephrotoxic drugs.
Allopurinol versus rasburicase
| Feature | Allopurinol | Rasburicase |
|---|---|---|
| Action | Xanthine oxidase inhibitor: stops new urate being made | Recombinant urate oxidase: breaks existing urate into soluble allantoin |
| Effect on existing urate | None | Rapid, large fall |
| Use | Prevention in low/intermediate risk | Prevention in high risk and treatment of established TLS |
| Key cautions | Builds up xanthine (can form xanthine stones); reduce azathioprine / mercaptopurine dose; severe skin reactions | Contraindicated in G6PD deficiency (haemolysis, methaemoglobinaemia); can falsely lower urate in blood samples left at room temperature |
Rasburicase works because humans lack urate oxidase; it converts uric acid to allantoin, which is far more soluble and easily excreted.
Urine alkalinisation with bicarbonate is no longer recommended: it can make calcium phosphate and xanthine crystals form in the kidney.
Management of established TLS
- Stop and reassess: senior and renal team involvement; continuous ECG monitoring.
- IV fluids to maintain urine output (if not overloaded).
- Rasburicase for high urate.
- Hyperkalaemia (the most dangerous problem):
- IV calcium gluconate to protect the heart if ECG changes.
- Insulin with glucose and nebulised salbutamol to shift potassium into cells.
- Remove potassium: dialysis if refractory.
- Hyperphosphataemia: phosphate binders, avoid phosphate intake; dialysis if severe.
- Hypocalcaemia: treat only if symptomatic (tetany, seizures, arrhythmia), because giving calcium when phosphate is high can deposit calcium phosphate in tissues and kidney.
- Renal replacement therapy (dialysis) for refractory hyperkalaemia, severe hyperphosphataemia, fluid overload, oliguria or uraemia.
Complications and prognosis
- Acute kidney injury (may need dialysis, usually recovers).
- Sudden cardiac death from hyperkalaemia.
- Seizures.
- Delay to cancer treatment.
With proper prevention, severe TLS is uncommon; established TLS with kidney failure carries a significant mortality.
Expect: the electrolyte pattern (high potassium, phosphate and urate with low calcium); a patient with Burkitt lymphoma or ALL who develops oliguria or arrhythmia after the first chemotherapy; the mechanism of kidney injury (urate and calcium phosphate crystals); hydration as the key preventive step; allopurinol (xanthine oxidase inhibitor) versus rasburicase (urate oxidase to allantoin); rasburicase contraindicated in G6PD deficiency; hyperkalaemia as the most immediately dangerous feature and its emergency treatment; and indications for dialysis.
Quick revision
- Rapid tumour cell death → K+ up, phosphate up, urate up, calcium down.
- Usually within days of starting chemotherapy; may be spontaneous.
- High risk: Burkitt, ALL, AML with high count, bulky high-grade lymphoma, high LDH, dehydration, renal impairment.
- Kidney injury: urate and calcium phosphate crystals in tubules.
- Prevent: IV hydration + allopurinol (lower risk) or rasburicase (high risk).
- Rasburicase: urate → allantoin; not in G6PD deficiency.
- Hyperkalaemia: calcium gluconate, insulin-glucose, salbutamol, dialysis.
- Treat low calcium only if symptomatic; avoid urine alkalinisation.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
Why does calcium fall in tumour lysis syndrome?
Large amounts of phosphate are released from dying cells; phosphate binds calcium and precipitates as calcium phosphate, lowering the blood calcium.
Which tumour is most associated with tumour lysis syndrome?
Burkitt lymphoma, followed by acute lymphoblastic leukaemia and other bulky, fast-growing, chemo-sensitive blood cancers.
How does rasburicase differ from allopurinol?
Allopurinol blocks xanthine oxidase so less new urate is made, whereas rasburicase is an enzyme that breaks down urate already present into soluble allantoin.
Why is rasburicase avoided in G6PD deficiency?
Its breakdown of urate produces hydrogen peroxide, which causes haemolysis and methaemoglobinaemia in people with G6PD deficiency.
When is dialysis needed in tumour lysis syndrome?
For hyperkalaemia or hyperphosphataemia not controlled by medical treatment, fluid overload, oliguria or worsening kidney failure.