OncologyTier 1Disease (DEADMAN)

Tumour lysis syndrome (TLS)

Description

Massive tumour cell lysis -> intracellular contents dumped into the circulation faster than the kidney can clear them
The one oncological emergency you can prevent - anticipation beats treatment

The metabolic quartet

Abnormality	Mechanism
inc K+	Released from cells; *the earliest lethal derangement*
inc phosphate	Released from cells (blasts contain 4x the phosphate of normal lymphocytes)
dec Ca2+	Secondary - calcium-phosphate complexing; do not correct unless symptomatic
inc urate	Nucleic acid -> purine -> xanthine -> uric acid

-> AKI from urate crystal nephropathy + calcium-phosphate deposition + volume depletion
-> arrhythmia, seizure, tetany, death

Highest risk: Burkitt lymphoma, ALL, high-count AML, aggressive NHL
Increasingly seen in previously low-risk disease with newer agents: venetoclax in CLL (the classic modern cause), obinutuzumab, CAR-T, bispecifics
Can occur spontaneously before any treatment in very high-turnover disease
Rare in solid tumours - but reported with bulky, chemo-sensitive disease (germ cell, small cell)

High tumour burden + high proliferative rate + high chemosensitivity
Lysis -> release of K+, phosphate, nucleic acids
Nucleic acid -> hypoxanthine -> xanthine -> uric acid (xanthine oxidase)
- Uric acid is poorly soluble in acid urine -> crystallises in distal tubules
Phosphate x calcium product exceeded -> calcium phosphate precipitation in tubules and soft tissue
- -> secondary hypocalcaemia
Volume depletion and pre-existing CKD amplify everything
Allopurinol blocks xanthine oxidase -> prevents new urate but causes xanthine accumulation, which can itself crystallise; it does not remove urate already formed

Cairo-Bishop criteria

Laboratory TLS - >=2 of the following within 3 days before to 7 days after therapy:

Clinical TLS = laboratory TLS plus one of:

Risk stratification determines prophylaxis

High: Burkitt, lymphoblastic lymphoma, ALL with WCC >100, AML with WCC >100, bulky chemosensitive disease, pre-existing renal impairment, venetoclax ramp-up in high-burden CLL
Intermediate: AML WCC 25-100, DLBCL with bulk, CLL on targeted therapy
Low: most solid tumours, indolent lymphoma

Monitoring

UEC, calcium, phosphate, magnesium, urate, LDH every 4-6 hours for 24-48 h after starting treatment in high-risk patients
Continuous cardiac monitoring if K+ raised
Urine output hourly

A. Prevention - where the work is

Identify risk BEFORE the first dose
Aggressive IV hydration - 2-3 L/m2/day (or 3 mL/kg/h), aiming urine output >=100 mL/m2/h
- The single most effective intervention
- *Do not alkalinise urine routinely* - improves urate solubility but promotes calcium-phosphate precipitation
Avoid nephrotoxins, contrast, and potassium/phosphate-containing fluids
Urate-lowering:

Risk	Agent
Low	Hydration +/- allopurinol
Intermediate	Allopurinol 300 mg daily (renally adjusted), start 24-48 h before therapy
High, or urate already raised, or established TLS	Rasburicase 3 mg or 0.2 mg/kg IV

Rasburicase = recombinant urate oxidase; converts urate -> allantoin (highly soluble); works within hours
- *Contraindicated in G6PD deficiency - haemolysis and methaemoglobinaemia* (screen at-risk ancestry; do not delay in an emergency)
- Sample must go on ice - rasburicase degrades urate in the tube -> spuriously low result
Cytoreduce gently in very high burden - steroid prephase in lymphoma, hydroxyurea/leukapheresis in hyperleukocytosis, venetoclax ramp-up over 5 weeks with dose interruption

B. Established TLS

Hyperkalaemia is what kills - treat immediately
- Calcium gluconate for ECG changes, insulin/dextrose, salbutamol, resonium/sodium zirconium
Hyperphosphataemia - oral phosphate binder; the definitive treatment is dialysis
*Hypocalcaemia: treat ONLY if symptomatic (tetany, seizure, arrhythmia)*
- Giving calcium into a high-phosphate milieu -> more calcium-phosphate deposition and worse AKI
Rasburicase for hyperuricaemia
Continue aggressive fluids; loop diuretic only if volume-replete and oliguric

C. Renal replacement therapy - discuss early with nephrology

Indications:
- Refractory hyperkalaemia
- Severe hyperphosphataemia with symptomatic hypocalcaemia
- Oliguric AKI / fluid overload
- Refractory acidosis or uraemia
Threshold to dialyse is lower than in other AKI - the metabolic load keeps arriving

Burkitt lymphoma, lymphoblastic lymphoma, ALL, AML with hyperleukocytosis
Venetoclax in CLL/AML - the commonest contemporary trigger
Obinutuzumab, rituximab in bulky disease, CAR-T, bispecific T-cell engagers
Corticosteroids alone in lymphoma/ALL (a "test dose" of prednisolone can precipitate it)
Radiotherapy to bulky disease, surgery, embolisation
Pre-existing CKD, volume depletion, nephrotoxins
G6PD deficiency - contraindication to rasburicase

Onset 12-72 hours after starting therapy; may be delayed with slower cytoreduction
With prophylaxis, clinical TLS is uncommon; without it, mortality up to 20-30% once AKI is established
Most AKI is reversible if managed early; some require temporary dialysis
*Prognosis is determined by whether the risk was recognised before the first dose, not by the treatment given after*
Risk period usually resolves by day 5-7 as tumour bulk falls

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