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.
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.