Tumour Lysis Syndrome
An oncological emergency caused by rapid cell death (spontaneous or treatment-induced) releasing intracellular contents, leading to hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia, with risk of AKI and fatal arrhythmias.
Key Facts
Cairo-Bishop criteria define laboratory TLS (≥2 of: uric acid ≥476 µmol/L, K⁺ ≥6.0, phosphate ≥1.45, Ca²⁺ ≤1.75) and clinical TLS (lab TLS + AKI, seizures, or arrhythmia) Highest risk: Burkitt lymphoma, ALL, high-count AML (WCC >100), bulky DLBCL Prevention: aggressive IV hydration (3 L/m²/day), rasburicase 0.2 mg/kg IV (recombinant urate oxidase) for high-risk patients Allopurinol 300mg TDS for intermediate-risk prophylaxis — prevents NEW uric acid formation but does not break down existing uric acid Rasburicase converts uric acid to allantoin (water-soluble) — rapid onset within 4 hours; contraindicated in G6PD deficiency Avoid calcium replacement unless symptomatic (risk of calcium-phosphate precipitation in renal tubules) Haemodialysis for refractory hyperkalaemia, severe AKI, or refractory metabolic abnormalities Mortality: untreated TLS has mortality of ~30–50%; with prevention and early management, mortality <5%
Overview
Key Facts
Tumour lysis syndrome (TLS) occurs when rapid destruction of malignant cells releases intracellular contents (potassium, phosphate, nucleic acids) into the bloodstream, overwhelming homeostatic mechanisms. It most commonly occurs 12–72 hours after initiation of cytotoxic therapy.
Epidemiology
- Incidence varies by tumour type: 4–42% in high-risk haematological malignancies
- Burkitt lymphoma/ALL: risk up to 25–40%
- Solid tumours: rare but reported with bulky, chemo-sensitive tumours (small cell lung cancer)
- Mortality: <5% with appropriate prophylaxis; up to 30–50% if untreated
Aetiology
- Treatment-induced: cytotoxic chemotherapy (most common), radiotherapy, glucocorticoids, targeted therapies (venetoclax, obinutuzumab)
- Spontaneous TLS: large, rapidly proliferating tumours (esp. Burkitt lymphoma)
- Risk factors: high tumour burden, high proliferative rate, elevated baseline LDH/uric acid, pre-existing renal impairment, dehydration, nephrotoxic drugs
Pathophysiology
- Rapid cell lysis → release of intracellular K⁺, phosphate, and nucleic acids
- Nucleic acid metabolism → hypoxanthine → xanthine → uric acid (via xanthine oxidase)
- Uric acid crystallises in renal tubules at acid pH → obstructive uropathy → AKI
- Hyperphosphataemia → calcium-phosphate precipitation in tissues → hypocalcaemia and further renal injury
- Hyperkalaemia → cardiac arrhythmias (the most immediate life-threatening complication)
- Hypocalcaemia → tetany, seizures, QT prolongation
Clinical Presentation
Typical Presentation
- Usually occurs 12–72 hours after starting chemotherapy
- Nausea, vomiting, diarrhoea
- Lethargy, weakness
- Oliguria or anuria
- Muscle cramps, tetany (hypocalcaemia)
Cardiac Manifestations
- Palpitations, arrhythmias (hyperkalaemia)
- QT prolongation (hypocalcaemia)
- Cardiac arrest
Renal Manifestations
- Acute kidney injury (rising creatinine, oliguria)
- Flank pain (uric acid crystal deposition)
Neurological Manifestations
- Seizures (hypocalcaemia)
- Paraesthesiae, Chvostek and Trousseau signs
- Confusion
Red Flags
- K⁺ ≥6.0 mmol/L with ECG changes
- Anuric renal failure
- Seizures
- Cardiac arrhythmias
- Rapidly rising creatinine after chemotherapy initiation
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| AKI (other causes) | No electrolyte pattern of TLS, different context | U&Es, uric acid, phosphate, calcium |
| Hyperkalaemia (other) | Medication-related, CKD, adrenal insufficiency | Medication review, cortisol |
| Rhabdomyolysis | Muscle pain, very high CK (>10,000), myoglobinuria | CK, urine myoglobin |
| Acute phosphate nephropathy | Post-phosphate enema, renal failure | History, phosphate level |
| DIC | Bleeding, coagulopathy, thrombocytopenia | PT, APTT, fibrinogen, D-dimer |
| Contrast-induced nephropathy | Recent contrast, AKI without TLS pattern | History, timing, U&Es |
Diagnosis / Investigation
Bedside
- ECG: peaked T waves (hyperkalaemia), prolonged QT (hypocalcaemia)
- Fluid balance: strict input/output monitoring
- VBG: rapid potassium and pH
Bloods
- U&Es: potassium (↑), creatinine (↑), urea (↑)
- Phosphate: elevated (≥1.45 mmol/L)
- Calcium (corrected): low (≤1.75 mmol/L)
- Uric acid: elevated (≥476 µmol/L)
- LDH: massively elevated (tumour burden marker)
- FBC: assess for cytopenias
- Coagulation: DIC screening
- ABG: metabolic acidosis
Imaging
- Renal USS: exclude obstructive cause if AKI
- CXR: pulmonary oedema if fluid overloaded
Special Tests
- Cairo-Bishop classification: laboratory vs clinical TLS
- G6PD screen: BEFORE rasburicase administration (contraindicated in G6PD deficiency)
- Bloods at minimum every 6–8 hours for first 48–72 hours of treatment
Management
Non-pharmacological
- Aggressive IV hydration: 3 L/m²/day (or 200 ml/hr in adults) with 0.9% NaCl — start 24–48 hours before chemotherapy
- Strict fluid balance: aim for urine output ≥2 ml/kg/hr
- Cardiac monitoring: continuous ECG for hyperkalaemia
- Avoid urinary alkalinisation: no longer recommended (may worsen calcium-phosphate deposition)
Pharmacological
Prophylaxis (risk-stratified):
- Low risk: hydration + monitoring
- Intermediate risk: hydration + allopurinol 300mg TDS (start 1–2 days before chemo, continue 7–10 days)
- High risk: hydration + rasburicase 0.2 mg/kg IV single dose (can repeat if needed); reduces uric acid within 4 hours
Treatment of established TLS:
- Rasburicase 0.2 mg/kg IV if not already given (contraindicated in G6PD deficiency — use allopurinol instead)
- Hyperkalaemia: calcium gluconate 10% 30ml IV, insulin 10U + glucose 25g IV, salbutamol nebs 10–20mg, calcium resonium
- Hyperphosphataemia: phosphate binders (sevelamer 800mg TDS, calcium carbonate); avoid aluminium-containing binders
- Hypocalcaemia: only treat if symptomatic (seizures, tetany) — IV calcium gluconate cautiously (risk of calcium-phosphate precipitation)
Surgical/Interventional
- Haemodialysis: for refractory hyperkalaemia (K⁺ >6.5), severe AKI (oliguric/anuric), refractory hyperphosphataemia, fluid overload
- Continuous renal replacement therapy (CRRT): preferred in haemodynamically unstable patients
Referral Criteria
- Renal team: all established clinical TLS, AKI requiring dialysis
- ICU: cardiac arrhythmias, multi-organ failure, need for CRRT
- Haematology/oncology: all cases (treatment plan modification may be needed)
Prognosis
- With appropriate prophylaxis: mortality <5%
- Untreated clinical TLS: mortality 30–50%
- AKI requiring dialysis: ~30% mortality
- Most cases resolve within 5–7 days with supportive care
- Long-term renal damage uncommon if managed promptly
- Prognosis primarily determined by underlying malignancy rather than TLS itself
- Spontaneous TLS carries worse prognosis than treatment-induced (often indicates aggressive disease)
Other Relevant Information
Cairo-Bishop Classification
| Parameter | Laboratory TLS Threshold |
|---|---|
| Uric acid | ≥476 µmol/L (or 25% increase) |
| Potassium | ≥6.0 mmol/L (or 25% increase) |
| Phosphate | ≥1.45 mmol/L (or 25% increase) |
| Calcium | ≤1.75 mmol/L (or 25% decrease) |
| Lab TLS | ≥2 abnormalities within 3 days before or 7 days after treatment |
| Clinical TLS | Lab TLS + AKI (creatinine ≥1.5× ULN), seizures, or cardiac arrhythmia/death |
TLS Risk Stratification
| Risk Level | Tumour Type | Prophylaxis |
|---|---|---|
| High | Burkitt, ALL (WCC >100), bulky DLBCL, AML (WCC >100) | Rasburicase + IV hydration |
| Intermediate | AML (WCC 25–100), ALL (WCC 50–100), DLBCL | Allopurinol + IV hydration |
| Low | Solid tumours, indolent lymphoma, CLL | Hydration + monitoring |