Tumour Lysis Syndrome (TLS)

BSH Updated guidelines for the diagnosis and management of tumour lysis syndrome in adults and children. Last revised: Dec 2025.

Article Last Updated:16/03/2026

Definition

TLS is a potentially life-threatening complication of haematological cancers that occurs when the large-scale destruction of malignant cells releases intracellular contents into the circulation.

Aetiology

There are 2 main primary mechanisms:

Following the administration of anti-cancer treatment
- Historically associated with cytotoxic chemotherapy
- Also increasingly associated with immunotherapies and novel targeted agents
- (e.g. cytotoxic chemotherapy, immunotherapies, targeted agents)
TLS can also occur spontaneously (i.e. without preceding anti-cancer treatment)
- Typically seen in malignancies with a very high proliferative rate (esp. Burkitt lymphoma)

The following factors put patients at higher risk of developing TLS.

The following haematological conditions are considered high risk:

High-grade lymphomas (esp. if advanced stage / bulky disease / ↑ LDH level)
- Burkitt lymphoma ++
- Diffuse large B-cell lymphoma
- Mantel cell lymphoma
- Adult T-cell leukaemia/lymphoma
Acute leukaemias (esp. if WBC ≥100 x 10⁹/L)

Certain pre-existing patient factors:

Renal impairment
Dehydration
Baseline laboratory abnormalities (e.g. hyperuricaemia, hyperphosphataemia, hyperkalaemia)
Specific novel agents
- Venetoclax (BCL-2 inhibitor) – primarily used to treat CLL and AML
- CAR T-cell therapy – primarily used to treat multiple myeloma

Pathophysiology

Massive and rapid destruction of malignant cells releases the following intracellular components into the circulation:

Phosphate → hyperphosphataemia and secondary hypocalcaemia (due to calcium binding to the released phosphate to form calcium-phosphate crystals)
Potassium → hyperkalaemia
Nucleic acid → converted to uric acid → hyperuricaemia

Clinical Manifestation

Metabolic abnormality	Clinical manifestation
Hyperphosphataemia	AKI (from calcium phosphate crystals)
Hypocalcaemia	Paraesthesia Tetany Seizures
Hyperkalaemia	Arrhythamias Sudden cardiac death
Hyperuricaemia	AKI (from uric acid crystals)

Investigation and Diagnosis

There are 2 diagnostic criteria for TLS:

Laboratory TLS – identifies the metabolic abnormalities before end-organ complications develop (i.e. before clinical manifestations occur)
Clinical TLS – indicates end-organ complications resulting from these metabolic abnormalities

Laboratory TLS Criteria

Defined by the presence of at least 2 of the following metabolic abnormalities, occurring within 3 days before or up to 7 days after initiation of anti-cancer treatment:

Metabolic abnormality (trend)	Exact cut-offs
↑ Phosphate	$\geq$ 2.1 mmol/L (in children) / $\geq$ 1.45 mmol/L (in adults), or 25% increase from baseline
↓ Calcium	≤1.75 mmol/L, or 25% decrease from baseline
↑ Potassium	$\geq$ 6.0 mmol/L, or 25% increase from baseline
↑ Uric acid	$\geq$ 476 $μ$ mol/L, or 25% increase from baseline

For exam purposes, it is more important to recognise the trends of metabolic abnormalities in TLS, rather than memorising the exact diagnostic cut-off values.

Clinical TLS Criteria

Clinical TLS is diagnosed when:

The laboratory TLS criteria (see above) are met, and
At least 1 of the following clinical complications is present:
- Renal impairment (serum creatinine ≥1.5 × the upper limit of normal)
- Cardiac arrhythmia
- Seizure
- Sudden death

Management

Prevention

There are 2 main corestones in preventing TLS:

Optimise hydration

Starting from the day before anti-cancer treatment:

Patient should drink 2-3 L of water / day (or 2.5-3 L/m² / day in children)
IV fluids are necessary for those who are at high risk or unable to maintain oral intake
Avoid potassium and phosphate supplementation

Uricosuric medications (drugs that reduce serum uric acid level)

Key prophylactic medications:

Allopurinol (preferred) / febuxostat – 1st line in mild to moderate risk cases
Rasburicase – used in high-risk cases

Acute Management

TLS is a potentially life-threatening oncological emergency, it requires urgent multidisciplinary management, involving haematologists, nephrologists, and intensive care teams.

Corestone of management	Aggressive IV hydration Promotes renal perfusion and uric acid excretion Helps prevent crystal precipitation and AKI
Hyperphosphataemia	No specific treatment Usually improves with aggressive IV hydration Phosphate binders have limited efficacy in TLS
Hypocalcaemia	IV calcium gluconate should only be given if the patient is symptomatic (e.g. seizures) To avoid precipitation of calcium-phosphate crystals
Hyperkalaemia	For moderate to severe hyperkalaemia: IV calcium gluconate if ECG changes are present Insulin + dextrose infusion Nebulised salbutamol Potassium binders See the Hyperkalaemia article for more information
Hyperuricaemia	Give rasburicase Rapidly reduces uric acid levels Stop allopurinol once rasburicase is started

If the above management fails / renal failure develops / refractory metabolic abnormalities → consider dialysis

The threshold for initiating dialysis is lower than in many other conditions, due to the ongoing and rapid release of intracellular contents.

References

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