Tumour lysis syndrome

Definition and mechanism. An oncological emergency caused by massive lysis of tumour cells, spontaneously or after cytotoxic therapy, releasing intracellular contents into the circulation faster than the kidney can clear them. This produces hyperuricaemia, hyperkalaemia, hyperphosphataemia and secondary hypocalcaemia, with acute kidney injury from uric acid and calcium phosphate crystal deposition.

Risk factors. High tumour burden and rapid proliferation — Burkitt lymphoma, acute lymphoblastic leukaemia, high-grade non-Hodgkin lymphoma, AML with high white cell count, and CLL treated with venetoclax; high sensitivity to therapy; bulky disease with raised LDH; and patient factors — pre-existing chronic kidney disease, dehydration, oliguria, hyperuricaemia and nephrotoxic drugs. Older patients are at higher risk because of reduced GFR and lower physiological reserve. Solid tumours rarely cause it.

Cairo-Bishop definitions. Laboratory TLS — two or more of the following within 3 days before to 7 days after chemotherapy: uric acid ≥8 mg/dL, potassium ≥6 mmol/L, phosphate ≥4.5 mg/dL, or calcium ≤7 mg/dL (or a 25% change from baseline). Clinical TLS — laboratory TLS plus acute kidney injury (creatinine ≥1.5× upper limit of normal), cardiac arrhythmia or sudden death, or seizure.

Clinical features. Nausea, vomiting, lethargy, oliguria and fluid overload; hyperkalaemia causing muscle weakness, paraesthesiae, peaked T waves, widened QRS and cardiac arrest; hypocalcaemia causing tetany, carpopedal spasm, Chvostek and Trousseau signs, prolonged QT and seizures; and acute kidney injury. Symptoms typically appear 12–72 hours after starting treatment.

Prevention (the most important element). Risk-stratify every patient before chemotherapy. Give aggressive intravenous hydration with 2–3 litres/m²/day of normal saline to maintain a urine output of 80–100 mL/m²/hour — started 24–48 hours before treatment and continued for 48–72 hours afterwards, with careful monitoring for fluid overload in older patients with heart failure. Allopurinol 300 mg daily (a xanthine oxidase inhibitor, renally dose-adjusted) for low and intermediate risk; rasburicase (recombinant urate oxidase, which converts uric acid to allantoin) for high risk or established TLS — it acts within hours, unlike allopurinol which only prevents new urate formation. Rasburicase is contraindicated in G6PD deficiency (haemolysis and methaemoglobinaemia) — screen first, which is particularly relevant in India. Urinary alkalinisation is no longer recommended because it promotes calcium phosphate precipitation. Stop nephrotoxins and monitor biochemistry 6–12 hourly.

Treatment of established TLS. Continue vigorous hydration and rasburicase; treat hyperkalaemia with calcium gluconate for cardioprotection, insulin-dextrose, salbutamol nebulisation and potassium binders; treat hyperphosphataemia with oral phosphate binders; and treat hypocalcaemia only if symptomatic, because giving calcium in the presence of a high phosphate promotes further calcium phosphate deposition. Refer early for renal replacement therapy — indications are refractory hyperkalaemia, severe hyperphosphataemia, volume overload, uraemia or persistent oliguria; the threshold for dialysis should be lower in the elderly. Manage jointly with nephrology and critical care.

TLS in the era of targeted therapy and evidence for lower rasburicase dosing. TLS is now an important toxicity of venetoclax in CLL and AML, which is why venetoclax must be given by a graded weekly dose ramp-up (20 → 50 → 100 → 200 → 400 mg) with risk-adapted hydration, uric acid-lowering therapy and inpatient monitoring for high tumour burden; it also occurs with CAR T-cell therapy and bispecific antibodies. In parallel, multiple studies support a single fixed low dose of rasburicase (3–6 mg) rather than daily weight-based dosing for 5 days, achieving equivalent urate control at a fraction of the cost — an important consideration in Indian practice.