Tumour Lysis Syndrome Prophylaxis

Tumour lysis syndrome follows rapid breakdown of cancer cells, releasing potassium, phosphate and nucleic acids, and causing hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia and acute kidney injury. It can cause arrhythmia and death within 12 to 72 hours of starting treatment. Prevention is much safer than treatment.

High-risk setting. Burkitt lymphoma, acute lymphoblastic leukaemia, acute myeloid leukaemia with white cell count over 50 x 10⁹/L, high-grade lymphoma with bulky disease or raised lactate dehydrogenase, chronic lymphocytic leukaemia on venetoclax with large nodes, and sensitive solid tumours with large bulk.

Pre-treatment risk factors. Baseline kidney impairment, dehydration, raised uric acid, high lactate dehydrogenase, large tumour burden and kidney infiltration.

Hydration (all patients at risk). Start 24 to 48 hours before chemotherapy: 0.9% sodium chloride or balanced crystalloid at 2.5 to 3 L/m2 daily, aiming for urine output of 100 mL/h or more (2 mL/kg/h in children). Add furosemide 20 to 40 mg IV only when fluid overloaded. Do not add potassium to fluids.

Low risk. Oral hydration and allopurinol 300 mg daily only if uric acid raised, with laboratory checks daily.

Intermediate risk. Allopurinol 300 mg daily (100 mg/m2 every 8 hours in children, maximum 800 mg daily), starting 1 to 2 days before treatment and continuing for 7 days or until the risk has passed.

High risk. Rasburicase 0.2 mg/kg IV over 30 minutes once daily for 1 to 7 days (often one to three doses are enough; 3 mg or 6 mg fixed doses are used in some units), starting before chemotherapy. Stop allopurinol while rasburicase is given. Contraindicated in glucose-6-phosphate dehydrogenase deficiency (test first or use allopurinol), and in pregnancy and breastfeeding. Collect uric acid samples on ice.

Alternative. Febuxostat 80 to 120 mg daily where allopurinol cannot be used and rasburicase is unavailable.

Do not alkalinise urine. It increases calcium phosphate precipitation and has no proven benefit.

Venetoclax. Ramp the dose over 5 weeks (20 mg, 50 mg, 100 mg, 200 mg, then 400 mg daily) with hydration and uric acid control.

Kidney impairment. Allopurinol: reduce to 100 mg daily when eGFR is 10 to 20 mL/min and give 100 mg on alternate days under 10 mL/min, titrating to uric acid. Rasburicase needs no adjustment. Febuxostat: maximum 40 mg daily in severe impairment. Early dialysis if oliguric.

Liver impairment. Allopurinol and febuxostat: lower doses.

Interactions. Allopurinol raises azathioprine and mercaptopurine levels (reduce by 75%); with ampicillin it increases rash risk. Rasburicase interferes with uric acid assays unless samples are on ice.

Treatment of established syndrome.

• Hyperkalaemia: calcium gluconate 10% 10 mL IV over 10 minutes for ECG changes, insulin 10 units with glucose 25 g IV, salbutamol 10 to 20 mg nebulised, and dialysis if refractory.
• Hypocalcaemia: treat only if symptomatic or with ECG change, since calcium can precipitate with phosphate.
• Hyperphosphataemia: phosphate binders (calcium-free) or dialysis.
• Acute kidney injury: renal replacement therapy early for persistent hyperkalaemia, volume overload, or phosphate over 6 mmol/L.

Pregnancy and breastfeeding. Hydration and allopurinol acceptable; avoid rasburicase and febuxostat.

Regional. Rasburicase is rarely available in East Africa; regard every high-burden patient as high risk and give aggressive hydration, allopurinol and dose-reduced or staged chemotherapy (steroid pre-phase), and arrange early transfer to a centre with dialysis. Tumours often present with large volume, and late diagnosis increases risk.

Laboratory checks. Potassium, phosphate, calcium, uric acid, creatinine and lactate dehydrogenase at baseline, then every 6 to 8 hours for 48 to 72 hours in high-risk patients, every 12 to 24 hours in intermediate risk. Cardiac monitoring if potassium is 6 mmol/L or more.

Fluid balance. Strict input and output, daily weights.

Stop and escalate. Start treatment of tumour lysis syndrome at the first laboratory sign (potassium 6 mmol/L or more, uric acid 476 micromol/L or more, phosphate 1.45 mmol/L or more, calcium 1.75 mmol/L or less, or a 25% change from baseline). Transfer to high-dependency care for arrhythmia, oliguria or creatinine rise. Continue prophylaxis until counts and tumour burden fall and laboratory values stay stable for 24 to 48 hours after the last chemotherapy dose.