Tumour Lysis Syndrome (TLS)

1. Definition

Tumour Lysis Syndrome (TLS) is a life-threatening oncologic emergency caused by the rapid destruction (lysis) of malignant cells, leading to the release of intracellular contents into the bloodstream. This results in electrolyte disturbances and acute kidney injury. TLS may occur spontaneously or after cytotoxic therapy (chemotherapy, targeted therapy, radiotherapy, steroids).

Diagnostic criteria are defined by Cairo-Bishop classification into laboratory TLS and clinical TLS.

2. Causes

Cause Type	Examples
Treatment-related	Chemotherapy (esp. induction therapy), steroids, immunotherapy, radiation
Spontaneous	Rare; may occur in aggressive leukemias/lymphomas before treatment
Triggers	Tumour manipulation, dehydration, infection

3. Risk Factors

Risk Factor	Notes
High tumour burden	Bulky disease, large lymph nodes
High proliferation rate	Burkitt lymphoma, acute lymphoblastic leukemia
High chemosensitivity	Lymphomas, leukemias
Pre-existing renal impairment	Lower threshold for AKI
Dehydration or hypotension	Reduces renal clearance of uric acid and phosphate
Elevated baseline LDH	Marker of tumour burden

4. Types / Classifications

Cairo-Bishop Criteria (2004)

Laboratory TLS (within 3 days before or 7 days after cytotoxic therapy):

2 or more of the following:
- Uric acid ≥ 476 μmol/L or 25% increase
- Potassium ≥ 6.0 mmol/L or 25% increase
- Phosphate ≥ 1.45 mmol/L or 25% increase
- Calcium ≤ 1.75 mmol/L or 25% decrease

Clinical TLS = Laboratory TLS + at least one of:

Creatinine ≥1.5 × ULN (AKI)
Seizure
Cardiac arrhythmia or sudden death

5. Pathogenesis

Massive cell lysis releases:
- Potassium → hyperkalemia → arrhythmias
- Phosphate → binds calcium → hypocalcemia → seizures, tetany
- Nucleic acids → metabolized to uric acid → hyperuricemia → crystal nephropathy
Urate and calcium phosphate crystals precipitate in renal tubules → AKI
Systemic metabolic disturbances → cardiac, neurologic, and renal complications

6. Clinical Presentation

Symptoms:

Nausea, vomiting
Lethargy, weakness
Muscle cramps or tetany
Seizures
Palpitations
Decreased urine output

Signs:

Hypotension
Arrhythmias (e.g., peaked T waves)
Tetany, Chvostek/Trousseau signs (hypocalcemia)
Oliguria or anuria

7. Organ & System Complications

System	Complication
Renal	AKI from uric acid or calcium phosphate nephropathy
Cardiovascular	Arrhythmias (from hyperkalemia/hypocalcemia)
Neurologic	Seizures, altered mental status
Musculoskeletal	Tetany, cramps
Hematologic	Coagulopathy (in some severe cases)

8. Diagnostic Investigations

Test	Purpose
Serum electrolytes	K⁺, PO₄³⁻, Ca²⁺, uric acid
Renal panel	Urea, creatinine
LDH	Marker of tumour burden
ECG	Detect hyperkalemia or hypocalcemia changes
Urinalysis	Assess for urate crystals

9. Other Relevant Investigations

ABG/VBG: to assess metabolic acidosis
Calcium-phosphate product: >70 increases risk of calcium phosphate precipitation
CBC: underlying malignancy, anemia, thrombocytopenia
Imaging (renal US): if obstructive uropathy or nephrolithiasis suspected

10. Treatment

Curative/Definitive:

Address and treat underlying malignancy (delay may worsen TLS)

Empirical:

Immediate IV hydration (2–3 L/m²/day) to maintain high urine output
Allopurinol (xanthine oxidase inhibitor): prevents uric acid formation
Rasburicase (urate oxidase): rapidly lowers existing uric acid
- Preferred in high-risk or established TLS

Supportive:

Electrolyte disturbance	Management
Hyperkalemia	Calcium gluconate, insulin + glucose, salbutamol, dialysis if needed
Hyperphosphatemia	Phosphate binders (e.g. sevelamer), avoid phosphate intake
Hypocalcemia	Only treat if symptomatic (to avoid calcium phosphate precipitation)
Uric acid elevation	Rasburicase preferred over allopurinol in established TLS

Dialysis indications:

Severe or refractory hyperkalemia
Persistent oliguria or anuria
Uremic symptoms
Volume overload
Life-threatening electrolyte imbalance

11. Long-Term Effects / Complications of Treatment

Complication	Treatment-Related Cause	Monitoring
Rasburicase hypersensitivity	G6PD-deficient patients	Avoid use, screen if high risk
Recurrent AKI	Inadequate hydration or late intervention	Monitor creatinine, urine output
Hypocalcemia-induced seizures	Overtreatment with phosphate binders or persistent hyperphosphatemia	Monitor Ca²⁺ and PO₄³⁻
Overhydration	Aggressive IV fluids	Daily weight, fluid balance

12. Surveillance for the Disease

Measure	Frequency
U&E, uric acid, phosphate, calcium	Every 6–12 hours in high-risk patients
ECG	Continuous if electrolyte abnormalities present
Fluid balance, urine output	Hourly during acute phase
LDH	As needed for tumour burden estimation
Repeat labs after cytotoxic therapy	Within 4–6 hours post-chemo

References

NHS/NICE Guidelines:
- UK Sepsis Trust and UK Oncology Nursing Society TLS Guidelines
- NHS England Acute Oncology guidelines
Malaysia Clinical Practice Guidelines:
- Ministry of Health Malaysia. Management of Adult Oncology Emergencies, MOH CPG 2016
  - https://www.moh.gov.my
UpToDate:
- “Tumor lysis syndrome: Clinical features, diagnosis, and management”
- “Prevention and treatment of tumor lysis syndrome in adults”