Tumour Lysis Syndrome
Tumour lysis syndrome is a potentially fatal metabolic emergency caused by rapid destruction of tumour cells, releasing intracellular contents and leading to hyperkalaemia, hyperuricaemia, hyperphosphataemia, and hypocalcaemia.
Key Facts
TLS results from rapid tumour cell lysis releasing potassium, phosphate, uric acid, and nucleic acids into the bloodstream Most commonly associated with haematological malignancies: Burkitt lymphoma, ALL, high-grade NHL (high tumour burden + rapid turnover) Cairo-Bishop classification: laboratory TLS (≥2 metabolic abnormalities) vs clinical TLS (lab TLS + organ dysfunction) Prevention is key: aggressive IV hydration (3L/m²/day) + allopurinol 300mg OD (prophylaxis) or rasburicase 0.2mg/kg IV (high-risk patients) Rasburicase converts uric acid to allantoin (highly soluble); rapid onset; contraindicated in G6PD deficiency (causes haemolysis) Hyperkalaemia is the most immediately life-threatening complication (cardiac arrhythmias, cardiac arrest) Avoid calcium supplementation for asymptomatic hypocalcaemia (risk of calcium phosphate precipitation in kidneys) Monitor U&Es, calcium, phosphate, urate, LDH every 6-8 hours during treatment initiation for high-risk patients
Overview
Key Facts
Tumour lysis syndrome is an oncological emergency resulting from the rapid release of intracellular contents following tumour cell destruction. Prevention, early detection, and aggressive management are essential to avoid life-threatening complications.
Epidemiology
- Incidence: 5-20% in high-risk haematological malignancies
- Rare in solid tumours (<1%) but reported in bulky/rapidly responsive disease (SCLC, germ cell tumours)
- Usually occurs within 12-72 hours of initiating treatment
- Can occasionally occur spontaneously in rapidly proliferating tumours
Aetiology
- High-risk: Burkitt lymphoma, ALL, high-grade NHL, CLL with bulky disease/high WCC
- Moderate-risk: AML, intermediate-grade NHL, CML in blast crisis
- Low-risk: most solid tumours, indolent lymphomas
- Risk factors: high tumour burden, high proliferative rate, high LDH, renal impairment, dehydration
Pathophysiology
- Rapid cell lysis releases intracellular potassium, phosphate, and nucleic acids
- Nucleic acid metabolism produces uric acid (via xanthine oxidase)
- Uric acid precipitates in renal tubules → acute uric acid nephropathy → AKI
- Hyperphosphataemia binds calcium → calcium phosphate deposition in kidneys and tissues → hypocalcaemia
- Hyperkalaemia → cardiac arrhythmias → cardiac arrest
- Hypocalcaemia → tetany, seizures, cardiac arrhythmias
Clinical Presentation
Metabolic Derangements
- Hyperkalaemia: muscle weakness, ECG changes (peaked T waves, widened QRS), cardiac arrhythmias
- Hyperuricaemia: flank pain, oliguria, haematuria (uric acid nephropathy)
- Hyperphosphataemia: often asymptomatic; contributes to renal failure
- Hypocalcaemia: muscle cramps, tetany (Chvostek/Trousseau sign), seizures, prolonged QT
Acute Kidney Injury
- Oliguria or anuria
- Rising creatinine
- Fluid overload
Red Flags
- Potassium >6.0 mmol/L with ECG changes
- Symptomatic hypocalcaemia (seizures, tetany)
- Anuria or rapidly rising creatinine
- Cardiac arrhythmias
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Pre-renal AKI (dehydration) | Clinical dehydration, responsive to fluids | U&Es, fluid challenge |
| Obstructive uropathy | Hydronephrosis, palpable bladder | Renal USS |
| Rhabdomyolysis | Muscle pain, raised CK, myoglobinuria | CK, urine myoglobin |
| Drug-induced AKI | Temporal relationship with nephrotoxic drug | Drug history |
| Primary hyperuricaemia (gout) | Joint inflammation, lower urate levels | Urate, joint aspiration |
Diagnosis / Investigation
Bedside
- ECG (hyperkalaemia changes: peaked T waves, prolonged PR, widened QRS, sine wave)
- Fluid balance chart (strict input/output)
- Blood pressure, observations
- Urinalysis
Bloods
- U&Es: potassium, creatinine (monitor every 6-8 hours in high-risk)
- Calcium and phosphate: monitor every 6-8 hours
- Uric acid: monitor every 6-8 hours
- LDH: marker of cell turnover
- Blood gas: acidosis (lactic acidosis from tissue ischaemia)
- FBC (WCC, platelets)
Imaging
- Renal USS: exclude obstruction if AKI
- CXR: fluid overload assessment
Special Tests
- Urine uric acid/creatinine ratio: >1.0 suggests uric acid nephropathy
- G6PD assay: BEFORE rasburicase administration (contraindicated in G6PD deficiency)
Management
Non-pharmacological
- Aggressive IV hydration: 3L/m²/day (0.9% saline); aim urine output >2 mL/kg/hour
- Cardiac monitoring (telemetry)
- Strict fluid balance
- Avoid potassium in IV fluids
- Consider ICU admission for severe TLS
- Renal replacement therapy (haemodialysis/haemofiltration) if: refractory hyperkalaemia, volume overload, severe AKI
Pharmacological
- Prevention (high risk): rasburicase 0.2mg/kg IV single dose (can repeat); aggressive hydration
- Prevention (moderate risk): allopurinol 300mg PO OD (start 24-48h before treatment); hydration
- Hyperkalaemia management:
- Calcium gluconate 10% 10mL IV over 10 minutes (cardiac protection)
- Insulin 10 units + 50mL 50% glucose IV (shift potassium intracellularly)
- Salbutamol 10-20mg nebulised
- Calcium resonium 15-30g PO or PR (slow onset)
- Hyperphosphataemia: phosphate binders (aluminium hydroxide 500mg TDS, sevelamer)
- Hypocalcaemia: only treat if symptomatic (seizures, tetany); IV calcium gluconate 10% 10-20mL over 10 minutes; avoid calcium if hyperphosphataemia present (precipitation risk)
- Hyperuricaemia: rasburicase 0.2mg/kg IV if not already given; allopurinol for mild cases
- Alkalinisation of urine is NO longer routinely recommended (may worsen calcium phosphate precipitation)
Surgical/Interventional
- Haemodialysis/haemofiltration: for refractory hyperkalaemia (>6.5 despite medical treatment), severe AKI (oliguria/anuria), volume overload, severe metabolic acidosis
- Nephrostomy if obstructive component
Referral Criteria
- All high-risk patients: haematology/oncology and renal team awareness before starting treatment
- Established TLS: renal team review
- ICU if multi-organ dysfunction
Prognosis
- With prevention and prompt treatment: mortality <5%
- Without treatment: mortality up to 50-80% (particularly with renal failure and hyperkalaemia)
- AKI requiring dialysis: approximately 5-10% of TLS cases
- Most metabolic derangements resolve within 5-7 days with appropriate treatment
- Long-term renal impairment is uncommon if managed promptly
Other Relevant Information
Cairo-Bishop TLS Classification
| Category | Criteria |
|---|---|
| Laboratory TLS | ≥2 of: uric acid >476 μmol/L (or 25% ↑), K+ >6.0 (or 25% ↑), PO₄ >1.45 (or 25% ↑), Ca²⁺ <1.75 (or 25% ↓) within 3 days before or 7 days after treatment |
| Clinical TLS | Lab TLS + ≥1 of: Cr >1.5× ULN, cardiac arrhythmia, seizures, death |
TLS Risk Stratification
| Risk | Examples | Prophylaxis |
|---|---|---|
| High | Burkitt lymphoma, ALL (WCC >100), bulky NHL | Rasburicase + aggressive hydration |
| Moderate | AML, intermediate NHL, CLL (high WCC) | Allopurinol + hydration |
| Low | Most solid tumours, indolent lymphomas | Hydration; consider allopurinol |