Tumour Lysis Syndrome(TLS) (bsh 2025)

3-6% of patients with high grade tumours. 1/3 need dialysis. 15% mortality

 

Definition

Laboratory TLS - ≥2 of the following occurring 3 days prior or 7 days post initiation of treatment for cancer:

  • Uric acid ≥476 umol/l or 25% increase from baseline

  • Potassium ≥6.0 mmol/l or 25% increase from baseline

  • Phosphate ≥1.45 mmol/l (adults) or 25% increase

  • Calcium ≤1.75 mmol/l or 25% decrease from baseline

Clinical TLS – Laboratory TLS plus at least one of:

  • Creatinine ≥1.5 x the ULN

  • Cardiac arrhythmia

  • Seizure

  • Sudden death

 

Biology

Metabolic syndrome caused by breakdown of malignant cells

Most likely to occur just prior to, or at start of, chemotherapy when disease most active

Excessive release of nucleic acids, proteins and intracellular metabolites from the tumour cells overwhelm the normal homostatic control mechanisms.

  • Hyperkalaemia occurs first and can be life threatening within 6 hours of onset of TLS

  • Uric acid crystals precipitate into the renal tubules, preventing the excretion of the other TLS metabolites. This creates a downward spiral of acute kidney failure.

 

Risk Factors

Disease histology - e.g. Burkitt lymphoma, Acute leukaemia

Disease burdern - ie. high tumour burden, pre-existing spontaneous TLS

Patient factors - e.g. CKD, Frailty, Increased Age, Other drugs that increase uric acid (alcohol, vit C, aspirin, caffeine, cisplatin, thiazides, levodopa, phenothiazines, theophylline.)

Treatment factors - e.g. Venetoclax for CLL, CAR-T therapies

—> Risk Stratification

(List is not exhaustive)

Low Risk

  • Clinical decision based on lack of risk factors and low tumour burden

  • e.g. Myeloma on alkylators/IMiD/PI/Antibody

  • e.g. CLL on BTKi / Alkylators

  • e.g. Low grade lymphoma or non-bulky High grade with a normal LDH

Intermediate Risk

  • Not high or low risk

  • e.g. Myeloma on CAR-T or bispecifics

  • e.g. Acute leukaemia with WBC <100

High Risk

  • AML or ALL with WBC >100

  • Burkitts leukaemia / lymphoma or ALL

  • High grade lymphoma with bulky disease (LDH 2x ULN or >10cm on CT)

  • Prior renal impairment or allopurinol allergy 

Drugs

 

Allopurinol/Febuxostat (Xanthine Oxidase Inhibitors)

  • Reduces production of uric acid by decreasing the rate of conversion of hypoxanthine to xanthine, and of xanthine to allopurinol.

  • Both hypoxanthine and xanthine are more soluble than uric acid and so less precipitation occurs in the renal tubules.

  • Does not increase rate of breakdown of uric acid that is already present so its therapeutic effect is delayed by 24-72 hours.

 

Rasburicase (Exogenous recombinant urate oxidase)

  • Recombinant form of mammalian urate oxidase. Not found in humans.

  • Metabolises urate to allantoin, a substance 10x more soluble than uric acid.

  • Acts immediately, and on any uric acid that is already formed.

  • Contra-indicated in G6PD deficiency (Risk of oxidative haemolysis)

  • Allopurinol should not be given together as its M.O.A may delay the effect of rasburicase.

tls.jpeg

Prophylaxis

General Principles

  • Patient Education

  • Avoidance of nephrotoxic drugs (e.g. NSAIDS, ACEi/ARB, SGLT2i, Metformin)

  • Monitoring (fluid balance / biochemical)

  • Hydration

  • Disease de-bulking, e.g. pre-phase steroids

  • Drugs to lower uric acid - allopurinol / febuxostat / rasburicase

Low Risk

  • Monitoring + 3L/24 hrs Hydration + consider omitting Allopurinol

Intermediate Risk

  • Monitoring + 3L/24 hrs Hydration + 7 days 300mg Allopurinol

High Risk

  • Monitoring + 3L/24 hrs Hydration + single dose 3mg Rasburicase

  • Monitoring bloods must be taken to lab on ice (rasburicase will continue to lower urate level in vitro at room temperature —> falsely reassuring result)

 

Treatment

 

MDT approach with haematology, renal and intensive care

Cardiac monitoring (calcium / potassium)

3L/m2 IV fluids to maintain high urine output >100ml/m2/hour

Rasburicase 0.2mg/kg/day, duration determine by clinical response

Dialysis if fluid overload / electrolytes uncontrolled (furosemide é uric acid deposition)

Hyperphosphataemia – nil specific

Hypocalcaemia – only treat if symptomatic

Hyperkalaemia – usually treatments but short-lived effect, likely need dialysis

uk safety review

NHS Englad Patient Safety team & Specialist Pharmacy Services (SPS) reviewed incidents of patient harm relating to delayed management of tumour lysis.

BSH 2025 guideline summarise the recommendations and the full 2024 report is here.