Write a short note on tumour lysis syndrome.

Definition

Tumour lysis syndrome (TLS) is an oncological emergency caused by the rapid release of intracellular contents into the circulation following massive tumour cell death — either spontaneously or, more commonly, shortly after starting cytotoxic therapy. It is characterised by a distinctive metabolic quartet with the potential for acute kidney injury, cardiac arrhythmia, seizures and death.

Pathophysiology — Four Derangements, Each with its Own Consequence

The two mechanisms of renal injury — urate nephropathy and calcium phosphate nephropathy — reinforce each other, and once renal function falls, potassium and phosphate rise further, creating a vicious cycle.

Risk Factors

Tumour-related:

• High-grade haematological malignancy with rapid turnover: Burkitt lymphoma, acute lymphoblastic leukaemia, high-grade non-Hodgkin lymphoma, acute myeloid leukaemia with high blast counts
• Large tumour bulk, extensive marrow involvement, high LDH, high white cell count
• Highly chemosensitive tumours — the more responsive the tumour, the greater the risk
• Rarely, bulky chemosensitive solid tumours (small cell lung cancer, germ cell tumours)

Patient-related: pre-existing renal impairment, dehydration or volume depletion, pre-treatment hyperuricaemia, acidic urine, and nephrotoxic drug exposure.

Treatment-related: initiation of chemotherapy, and also corticosteroids alone (which can lyse lymphoid tumours), radiotherapy, and targeted agents such as venetoclax, which caused TLS at high enough rates in chronic lymphocytic leukaemia to require a mandatory dose-ramp protocol.

Clinical Features

Usually within 12–72 hours of starting treatment, but may occur spontaneously before it:

• Often initially asymptomatic — detected only by biochemical monitoring, which is why at-risk patients must be monitored proactively.
• Nausea, vomiting, diarrhoea, anorexia, lethargy.
• Muscle cramps, tetany, paraesthesiae, carpopedal spasm (hypocalcaemia); positive Chvostek's and Trousseau's signs.
• Cardiac arrhythmia, palpitations, syncope, sudden death (hyperkalaemia, hypocalcaemia with QT prolongation).
• Seizures and altered consciousness.
• Oliguria, haematuria, flank pain, fluid overload — acute kidney injury.

Cairo–Bishop criteria define laboratory TLS (two or more abnormal values within 3 days before to 7 days after treatment) and clinical TLS (laboratory TLS plus renal impairment, arrhythmia, seizure or death).

Investigations

• Serial biochemistry — the mainstay: potassium, phosphate, calcium, uric acid, creatinine, urea and LDH, checked every 4–8 hours in high-risk patients during the first 24–72 hours of treatment.
• ECG and continuous cardiac monitoring — for hyperkalaemic changes (peaked T waves, widened QRS) and QT prolongation.
• Strict fluid balance and urine output monitoring; urinalysis for uric acid crystals.
• Baseline assessment of renal function and hydration before starting therapy.

Management

Prevention is far more effective than treatment, and risk stratification determines the intensity of prophylaxis.

1. Vigorous hydration — the single most important measure

Intravenous fluids started before and continued throughout chemotherapy, aiming for a high urine output to dilute urate and phosphate and maintain tubular flow. Avoid potassium-containing fluids. Monitor for fluid overload in cardiac and renal impairment; diuretics only for overload, not routinely.

2. Reduce uric acid

• Allopurinol — a xanthine oxidase inhibitor that prevents further uric acid formation but does not remove uric acid already present. Given to standard-risk patients, ideally starting 24–48 hours before chemotherapy. Reduce the dose in renal impairment, and note the interaction with azathioprine and 6-mercaptopurine (levels rise dangerously).
• Rasburicase — a recombinant urate oxidase that converts existing uric acid to the highly soluble allantoin, producing a rapid fall in urate within hours. It is the agent of choice for high-risk patients and for established TLS. Contraindicated in G6PD deficiency, where it causes severe haemolysis and methaemoglobinaemia — screen before use.

3. Correct the electrolyte abnormalities

• Hyperkalaemia — the immediate threat: calcium gluconate for cardiac protection, insulin-dextrose and salbutamol to shift potassium, and potassium binders or dialysis to remove it (see the hyperkalaemia answer).
• Hyperphosphataemia — oral phosphate binders; dialysis in severe cases.
• Hypocalcaemia — treat only if symptomatic, and cautiously, since giving calcium in the presence of a high phosphate promotes further calcium phosphate deposition in tissues and kidneys.
• Urinary alkalinisation is NO LONGER routinely recommended — although it increases uric acid solubility, it decreases calcium phosphate solubility and may worsen nephrocalcinosis, and it is unnecessary when rasburicase is available.

4. Renal replacement therapy

Indicated for refractory hyperkalaemia, severe or symptomatic hyperphosphataemia, fluid overload, uraemia, or oliguric acute kidney injury unresponsive to medical management. Have nephrology involved early in high-risk patients rather than after failure.

5. Modify the treatment

Consider a "pre-phase" of low-dose steroid or cyclophosphamide to reduce tumour bulk gradually before full chemotherapy in very high-risk patients, and use mandated dose-ramp schedules with agents such as venetoclax.