Overview
Tumour Lysis Syndrome
Topic Overview
Summary
Tumour lysis syndrome (TLS) is an oncological emergency caused by rapid release of intracellular contents (potassium, phosphate, nucleic acids) following chemotherapy-induced tumour cell death. It most commonly occurs with haematological malignancies (acute leukaemia, high-grade lymphoma). The metabolic derangements include hyperkalaemia, hyperuricaemia, hyperphosphataemia, and hypocalcaemia, leading to acute kidney injury, cardiac arrhythmias, seizures, and death. Prevention with hydration and allopurinol/rasburicase is key.
Key Facts
- Timing: Usually 12-72 hours after chemotherapy
- High-risk tumours: ALL, Burkitt lymphoma, high-grade NHL
- Metabolic abnormalities: ↑K+, ↑uric acid, ↑phosphate, ↓calcium
- Complications: AKI, arrhythmias, seizures
- Prevention: Hydration + allopurinol or rasburicase
Clinical Pearls
TLS can occur spontaneously (before treatment) in highly proliferative tumours
Rasburicase is contraindicated in G6PD deficiency (causes haemolysis)
Hypocalcaemia is secondary to hyperphosphataemia (calcium phosphate precipitation)
Why This Matters Clinically
TLS is preventable with appropriate prophylaxis. Once established, it is life-threatening. Early recognition and aggressive management saves lives.
Visual Summary
Visual assets to be added:
- TLS pathophysiology diagram
- Cairo-Bishop criteria table
- Risk stratification chart
- TLS prevention and management algorithm
Epidemiology
Incidence
- Varies by tumour type
- 5-20% of patients with high-grade haematological malignancies
High-Risk Tumours
| Tumour | Risk |
|---|---|
| Burkitt lymphoma | Very high |
| Acute lymphoblastic leukaemia (ALL) | High |
| High-grade NHL | High |
| Acute myeloid leukaemia (AML) | Moderate-high |
| CLL (treated with venetoclax) | Moderate |
| Solid tumours | Low (but possible with bulky disease) |
Risk Factors
| Factor | Notes |
|---|---|
| High tumour burden | Bulky disease |
| Rapidly proliferating tumour | High LDH |
| Pre-existing renal impairment | |
| Elevated baseline uric acid | |
| Dehydration |
Pathophysiology
Mechanism
- Chemotherapy causes rapid tumour cell death
- Intracellular contents released into bloodstream
- Metabolic derangements develop
Specific Abnormalities
| Abnormality | Mechanism | Consequence |
|---|---|---|
| Hyperkalaemia | K+ released from cells | Arrhythmias, cardiac arrest |
| Hyperuricaemia | Nucleic acid breakdown → uric acid | Uric acid nephropathy, AKI |
| Hyperphosphataemia | Phosphate released from cells | Calcium phosphate precipitation → AKI, hypocalcaemia |
| Hypocalcaemia | Binds to phosphate | Tetany, seizures, arrhythmias |
AKI Mechanisms
- Uric acid crystal deposition in tubules
- Calcium phosphate precipitation
- Direct nephrotoxicity
Clinical Presentation
Symptoms
Signs
Timing
Red Flags
| Finding | Significance |
|---|---|
| K+ over 6.0 | Cardiac risk |
| Oliguria/anuria | AKI |
| Seizures | Hypocalcaemia |
| Arrhythmias | Hyperkalaemia, hypocalcaemia |
Often asymptomatic initially (laboratory TLS)
Common presentation.
Nausea, vomiting
Common presentation.
Muscle cramps
Common presentation.
Weakness
Common presentation.
Confusion
Common presentation.
Seizures
Common presentation.
Palpitations
Common presentation.
Clinical Examination
General
- Confusion
- Weakness
Cardiovascular
- Arrhythmia
- Hypotension (if shocked)
Neurological
- Tetany
- Seizures
- Chvostek's sign (facial twitch on tapping)
- Trousseau's sign (carpopedal spasm on BP cuff)
Investigations
Blood Tests — Monitor 6-12 Hourly
| Test | Finding |
|---|---|
| Potassium | Elevated (over 6.0 = urgent) |
| Uric acid | Elevated |
| Phosphate | Elevated |
| Calcium | Low (corrected calcium) |
| Creatinine | Elevated (AKI) |
| LDH | Elevated (cell turnover) |
ECG
- Peaked T waves (hyperkalaemia)
- Prolonged QT (hypocalcaemia)
- Arrhythmias
Cairo-Bishop Criteria
Laboratory TLS (2 or more of):
- Uric acid over 476 μmol/L or 25% increase
- Potassium over 6.0 mmol/L or 25% increase
- Phosphate over 1.45 mmol/L or 25% increase
- Calcium under 1.75 mmol/L or 25% decrease
Clinical TLS:
- Laboratory TLS + AKI, seizures, arrhythmias, or death
Classification & Staging
Laboratory vs Clinical TLS
| Type | Definition |
|---|---|
| Laboratory TLS | Meets Cairo-Bishop criteria (no clinical manifestations) |
| Clinical TLS | Laboratory TLS + clinical consequences (AKI, arrhythmia, seizures) |
Risk Stratification
| Risk | Examples |
|---|---|
| High | Burkitt, ALL, high-grade NHL with bulky disease |
| Intermediate | AML, CLL with venetoclax, other NHL |
| Low | Solid tumours, indolent lymphoma |
Management
Prevention — Critical
Hydration (All Patients):
- IV fluids 2-3 L/m²/day starting 24-48h before chemotherapy
- Maintain urine output over 100 mL/m²/hr
Allopurinol (Low-Intermediate Risk):
- 300 mg PO daily
- Start 1-2 days before chemotherapy
- Prevents new uric acid formation
Rasburicase (High Risk):
- 0.2 mg/kg IV
- Recombinant urate oxidase
- Rapidly breaks down uric acid
- Contraindicated in G6PD deficiency (haemolysis)
Avoid:
- Thiazide diuretics (reduce uric acid excretion)
- Potassium supplements
Treatment of Established TLS
Hyperkalaemia:
- Calcium gluconate (cardiac protection)
- Insulin + dextrose
- Salbutamol nebuliser
- Calcium resonium
- Dialysis if refractory
Hyperuricaemia:
- Rasburicase if not already given
- Haemodialysis if refractory
Hyperphosphataemia:
- Phosphate binders
- Dialysis if severe
Hypocalcaemia:
- Only treat if symptomatic (precipitates with phosphate)
- Calcium gluconate IV
AKI:
- Haemodialysis — low threshold
- Correct metabolic abnormalities
Complications
Metabolic
- Life-threatening hyperkalaemia
- Severe hypocalcaemia
Renal
- Acute kidney injury
- Need for dialysis
Cardiac
- Arrhythmias
- Cardiac arrest
Neurological
- Seizures
Prognosis & Outcomes
Prognosis
- Good if prevented or recognised early
- Significant mortality if clinical TLS develops (10-20%)
Factors Affecting Outcome
- Time to recognition
- Access to dialysis
- Underlying disease
Evidence & Guidelines
Key Guidelines
- ASCO/NCCN Guidelines on TLS
- British Committee for Standards in Haematology (BCSH) Guidelines
Key Evidence
- Rasburicase is more effective than allopurinol for high-risk patients
- Aggressive hydration is the cornerstone of prevention
Patient & Family Information
What is Tumour Lysis Syndrome?
TLS happens when cancer cells break down very quickly after treatment, releasing their contents into the blood. This can cause dangerous changes in blood chemistry.
Who is at Risk?
- People with certain blood cancers like leukaemia or lymphoma
- People with large tumours
Prevention
- Lots of fluids through a drip
- Medication to protect the kidneys
Treatment
- Close monitoring of blood tests
- Medication to correct blood chemistry
- Sometimes dialysis is needed
Resources
References
Primary Guidelines
- Coiffier B, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome. J Clin Oncol. 2008;26(16):2767-2778. PMID: 18509186
Key Reviews
- Howard SC, et al. The tumor lysis syndrome. N Engl J Med. 2011;364(19):1844-1854. PMID: 21561350
- Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004;127(1):3-11. PMID: 15384972