tumour lysis syndrome

quick recognition

• rising K⁺, PO₄, uric acid with falling Ca²⁺ in a patient with known or suspected malignancy
• AKI (uric acid nephropathy, calcium-phosphate precipitation)
• arrhythmia (hypocalcaemia → QT prolongation → torsades de pointes), muscle cramps, tetany, seizure
• can occur before treatment (spontaneous TLS) — especially in high-grade lymphomas and leukaemias

risk stratification

risk	malignancy	features
high	Burkitt lymphoma, ALL, AML with WBC >100 × 10⁹/L	bulky disease, LDH >2× ULN, pre-existing renal impairment, uric acid already elevated
intermediate	other aggressive lymphomas, AML with WBC 25–100 × 10⁹/L	moderate tumour burden
intermediate–high	CLL/AML on venetoclax	specific ramp-up TLS protocols required — see venetoclax section below
low	indolent lymphomas, CLL (non-venetoclax), most solid tumours	low proliferation rate, small tumour burden

Risk amplifiers: dehydration, oliguria, nephrotoxic drugs, spontaneous TLS before treatment.

diagnosis (Cairo-Bishop criteria)

laboratory TLS (≥2 of the following within 3 days before or 7 days after initiation of therapy)

parameter	threshold (adults)
uric acid	≥476 μmol/L (≥8.0 mg/dL) or 25% increase
potassium	≥6.0 mmol/L or 25% increase
phosphate	≥1.5 mmol/L (≥4.5 mg/dL) or 25% increase
calcium (corrected)	<1.75 mmol/L (<7.0 mg/dL) or 25% decrease

clinical TLS

Laboratory TLS + ≥1 end-organ consequence:

• renal: creatinine ≥1.5× ULN
• cardiac: arrhythmia or sudden death
• neurological: seizure

prevention

Prevention is more effective than treatment — stratify risk before initiating chemotherapy.

hydration (all risk groups)

• aggressive IV NS aiming for 1–3 L/m²/day (higher end for highest-risk patients) — maintain high urine output (≥2 mL/kg/hr)
• no potassium in IV fluids
• no Ringer’s lactate (contains potassium)
• no bicarbonate — alkalinisation is no longer recommended (does not prevent uric acid nephropathy, may worsen calcium-phosphate precipitation)
• start 24–48 hours before chemotherapy if possible

urate-lowering therapy

risk	agent	notes
low	observation ± allopurinol	hydration alone may suffice
intermediate	allopurinol 300 mg PO daily (reduce if CrCl reduced)	prevents new uric acid formation; does not degrade existing uric acid. Febuxostat is an alternative if allopurinol hypersensitivity
high	rasburicase	degrades existing uric acid to soluble allantoin

rasburicase

• mechanism: recombinant urate oxidase — converts uric acid to allantoin (5–10× more soluble)
• dosing: centre-specific
  • weight-based: 0.1–0.2 mg/kg IV single dose (max 6 mg)
  • fixed-dose: 3–6 mg IV × 1 (increasingly used — non-inferior in studies, lower cost; 3 mg often sufficient for prophylaxis)
  • repeat only if uric acid rebounds

monitoring during induction

• K⁺, PO₄, Ca²⁺, uric acid, creatinine, LDH every 6–12 hours during high-risk period (first 48–72 hours) — increase frequency if metabolic derangement worsening
• strict fluid balance — input/output charting
• cardiac monitoring if hyperkalaemia or hypocalcaemia

management of established TLS

hyperkalaemia (most immediately lethal)

1. stabilise myocardium: calcium gluconate 10% 30 mL IV over 10 min (or calcium chloride via central line)
2. shift K⁺ intracellularly: insulin 10 units IV + dextrose 25 g IV; salbutamol 10–20 mg nebulised
3. eliminate K⁺: loop diuretics (if volume replete); sodium zirconium cyclosilicate (GI cation exchanger, preferred over sodium polystyrene sulfonate); dialysis if refractory or AKI — intermittent HD may be superior to CRRT for refractory hyperkalaemia (faster flow rates, larger dialysers)

hyperphosphataemia

• phosphate binders: sevelamer (preferred) or aluminium hydroxide
• do not use calcium carbonate — drives calcium-phosphate precipitation → nephrocalcinosis, soft tissue calcification
• dialysis often needed for severe or refractory hyperphosphataemia — CRRT preferred over intermittent HD (phosphorus removal is time-dependent; CRRT prevents rebound hyperphosphataemia)

hypocalcaemia

• treat only if symptomatic (tetany, Trousseau/Chvostek signs, seizures, arrhythmia)
• IV calcium replacement in the setting of hyperphosphataemia promotes calcium-phosphate precipitation in kidneys and soft tissues — avoid unless life-threatening symptoms
• correct phosphate first → calcium often self-corrects

hyperuricaemia

• rasburicase if not already given (check G6PD first)
• if rasburicase contraindicated: aggressive hydration + allopurinol (slower onset)
• dialysis for refractory cases

renal failure

• early nephrology consultation
• indications for CRRT/haemodialysis: refractory hyperkalaemia, volume overload unresponsive to diuretics, severe metabolic acidosis, rapidly rising creatinine
• modality selection: CRRT preferred for hyperphosphataemia (time-dependent clearance); intermittent HD may be better for refractory hyperkalaemia (faster flow rates)

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venetoclax-associated TLS

Venetoclax (BCL-2 inhibitor) carries significant TLS risk in CLL and AML due to rapid apoptosis induction.

• mandatory dose ramp-up over 5 weeks (CLL: 20 → 50 → 100 → 200 → 400 mg) with TLS prophylaxis at each step
• risk stratification based on tumour burden (lymphocyte count, lymph node size) determines inpatient vs outpatient monitoring
• hydration + allopurinol/febuxostat for all patients; rasburicase for high-risk
• labs (K⁺, PO₄, Ca²⁺, uric acid, creatinine) at 6–8 hours and 24 hours after each dose escalation
• refer to product monograph and institutional protocols for specific ramp-up schedules

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what NOT to do

• use calcium carbonate as phosphate binder → calcium-phosphate precipitation
• replace calcium aggressively in asymptomatic hypocalcaemia → nephrocalcinosis
• alkalinise urine with bicarbonate — outdated practice, worsens calcium-phosphate precipitation
• give rasburicase without checking G6PD → haemolytic crisis
• trust uric acid levels drawn at room temperature after rasburicase → falsely low
• delay chemotherapy excessively for TLS prophylaxis — definitive tumour treatment is the ultimate TLS treatment
• forget to hold potassium in IV fluids