Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is a life-threatening oncological emergency resulting from rapid destruction of malignant cells, leading to the release of intracellular potassium, phosphate, and nucleic acids into the circulation. The subsequent metabolic abnormalities include hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia, and acute kidney injury. TLS most commonly occurs after initiation of cytotoxic therapy but may also occur spontaneously in highly proliferative malignancies. Early identification of high-risk patients, preventive measures, and prompt treatment are essential to reduce morbidity and mortality.

Epidemiology

Tumor lysis syndrome occurs most commonly in rapidly proliferating and highly chemotherapy-sensitive malignancies, including:

• Burkitt lymphoma

• Acute lymphoblastic leukemia (ALL)

• Acute non-lymphocytic leukemia

• High-grade lymphomas

Less commonly, TLS occurs in solid tumors such as:

• Small-cell carcinoma

• Breast cancer

• Medulloblastoma

Risk factors

Risk factors include:

• Burkitt lymphoma

• Acute lymphoblastic leukemia

• Acute non-lymphocytic leukemia

• High-grade lymphoma

• Large tumor burden

• High serum lactate dehydrogenase (LDH)

• Pre-existing renal impairment

• Dehydration

• Highly effective chemotherapy

• Highly proliferative tumors

Pathophysiology

Tumor lysis syndrome develops following rapid destruction of malignant cells, releasing intracellular potassium, phosphate, and nucleic acids into the bloodstream. Purine nucleic acids are metabolized into uric acid, which may precipitate within renal tubules causing acute kidney injury. Hyperphosphataemia leads to calcium phosphate precipitation, resulting in hypocalcaemia and further renal injury. Hyperkalaemia may cause life-threatening cardiac arrhythmias.

Clinical presentation

Clinical manifestations range from asymptomatic laboratory abnormalities to severe metabolic disturbances and multiorgan dysfunction. Symptoms are related to electrolyte abnormalities and acute kidney injury.

Symptoms

• Nausea

• Vomiting

• Generalized weakness

• Muscle cramps

• Paraesthesia

• Tetany

• Reduced urine output

• Flank pain

• Palpitations

• Dyspnoea

• Confusion

• Seizures

Clinical signs

• Dehydration

• Cardiac arrhythmias

• Muscle twitching

• Tetany

• Positive Chvostek sign

• Positive Trousseau sign

• Altered mental status

• Reduced urine output

• Features of acute kidney injury

Differential diagnosis

• Acute kidney injury of other causes

• Sepsis

• Hyperkalaemia from renal failure

• Diabetic ketoacidosis

• Rhabdomyolysis

• Severe dehydration

• Drug-induced electrolyte disturbances

Diagnostic criteria

Tumor lysis syndrome is diagnosed by the presence of characteristic biochemical abnormalities occurring spontaneously or following treatment of malignancy, together with clinical manifestations when present.

Typical metabolic abnormalities include:

• Hyperuricaemia

• Hyperkalaemia

• Hyperphosphataemia

• Hypocalcaemia

• Acute kidney injury

Investigations

Laboratory investigations

• Full blood picture (FBP)

• Renal function tests (RFT)

• Liver function tests (LFT)

• Lactate dehydrogenase (LDH)

• Serum electrolytes

• Serum phosphate

• Serum calcium

• Serum uric acid

• Blood urea nitrogen (BUN)

• Serum creatinine

• Urine pH

• Urine output monitoring

Cardiac investigations

• Electrocardiogram (ECG)

Imaging

• Chest X-ray (CXR)

• CT scan where clinically indicated

• Abdominal and pelvic ultrasound (USS)

Management

Tumor lysis syndrome is a medical emergency requiring aggressive supportive care and correction of metabolic abnormalities.

Initial management includes:

• Assess airway, breathing, and circulation.

• Identify patients at high risk before chemotherapy.

• Initiate aggressive intravenous hydration.

• Closely monitor urine output.

• Correct electrolyte abnormalities promptly.

• Monitor cardiac rhythm continuously in patients with hyperkalaemia.

Non-pharmacological treatment

• Begin aggressive intravenous hydration 12–48 hours before chemotherapy in high-risk patients.

• Continue hydration for 48–72 hours after chemotherapy.

• Continuous intravenous fluids should exceed 3 L/m²/day, aiming for urine output of at least 3 L/day.

• Monitor urine output hourly.

• Monitor renal function and serum electrolytes frequently.

• Frequent laboratory monitoring should include:

  • Blood urea nitrogen (BUN)

  • Serum creatinine

  • Uric acid

  • Potassium

  • Sodium

  • Phosphate

  • Calcium

  • Lactate dehydrogenase (LDH)

These investigations should be performed at least three times daily.

Pharmacological treatment

Urine alkalinization

• Sodium bicarbonate – 100 mEq/L – IV – added to intravenous fluids – continued for 48–72 hours after initiation of chemotherapy.

Uric acid reduction

• Allopurinol – 300 mg/day – IV – once daily.

Hyperkalaemia

Patients with elevated serum potassium should undergo continuous cardiac monitoring.

• Administer calcium according to hyperkalaemia management guidelines.

• Administer cation exchange resins where indicated.

Persistent hypocalcaemia

• Calcitriol should be administered in patients with persistently low serum calcium levels.

Supportive therapy

• Empiric antibiotics should be administered when opportunistic infection is suspected.

• Total parenteral nutrition (TPN) should be considered where indicated.

• Neupogen (G-CSF) should be administered where clinically indicated.

Management according to underlying cause

High-risk patients before chemotherapy

• Initiate hydration 12–48 hours before chemotherapy.

• Begin Allopurinol prophylaxis.

• Frequent biochemical monitoring.

Established tumor lysis syndrome

• Aggressive intravenous hydration.

• Correct electrolyte abnormalities.

• Continuous cardiac monitoring for hyperkalaemia.

• Maintain adequate urine output.

• Manage acute kidney injury appropriately.

Acute kidney injury

• Optimize fluid balance.

• Correct metabolic abnormalities.

• Consider renal replacement therapy where indicated.

Opportunistic infection

• Administer empiric antibiotics according to local antimicrobial guidelines.

Referral

Urgently refer patients with tumor lysis syndrome to an oncology and critical care specialist.

Immediate referral is indicated for patients with:

• Severe hyperkalaemia

• Acute kidney injury

• Cardiac arrhythmias

• Oliguria or anuria

• Severe electrolyte abnormalities

• Seizures

• Altered level of consciousness

• Requirement for renal replacement therapy

Complications

• Acute kidney injury

• Cardiac arrhythmias

• Sudden cardiac death

• Seizures

• Tetany

• Metabolic acidosis

• Volume overload

• Multiorgan failure

• Death

Prognosis

The prognosis depends on early recognition, prompt initiation of preventive measures, severity of metabolic disturbances, and the underlying malignancy. With appropriate prophylaxis and aggressive supportive care, most cases are reversible. Delayed diagnosis or severe electrolyte abnormalities significantly increase morbidity and mortality.

Prevention

Prevention is the cornerstone of tumor lysis syndrome management. High-risk patients should be identified before chemotherapy and managed with aggressive intravenous hydration, prophylactic uric acid-lowering therapy, and frequent monitoring of electrolytes and renal function. Early recognition and treatment of metabolic abnormalities reduce the risk of life-threatening complications.