21st June 2023

Tumour lysis syndrome

Diagnosis

Tumour lysis syndrome (TLS) is a serious and potentially preventable oncological emergency which carries a profound risk of morbidity and mortality. The underlying mechanism is massive tumour cell lysis, typically seen in highly chemosensitive or bulky cancers in response to systemic anticancer therapy. The resulting cell breakdown causes the release of intracellular contents including nuclear material. Nucleic acids are broken down into uric acid, which precipitates in the renal tubules, causing severe acute kidney injury. Alongside this, large volumes of potassium and phosphate are released into circulation. In the presence of hyperphosphataemia, calcium is lost from the circulating volume as calcium phosphate precipitates in the renal tubules.

The Cairo-Bishop definition of biochemical TLS is any two of the following:

• Uric acid: >476 µmol/L
• K⁺: >6.0 mmol/L
• PO₄³⁻: >2.1 mmol/L
• Ca²⁺: <1.75 mmol/L

Commonly associated malignancies include:

• High-grade non-Hodgkin’s lymphoma – particularly Burkitt’s lymphoma
• Acute lymphoblastic leukaemia
• Acute myeloid leukaemia
• Chronic lymphocytic leukaemia
• Small cell carcinoma – particularly of the lung
• Germ cell tumours

Management

Pre-treatment factors should be considered to reduce the risk of developing TLS. Dehydration, oliguria, underlying intrinsic renal disease and pre-existing hyperuricaemia should be addressed. In those patients at very high risk of developing TLS, pre-treatment hydration, alongside prophylactic rasburicase is recommended. Rasburicase catalyses the oxidation of uric acid into allantoin, a soluble inactive metabolite, thus actively reducing serum uric acid levels. In those with an intermediate risk of TLS, pre-hydration and allopurinol should be employed. Allopurinol is a xanthine oxidase inhibitor, preventing the conversion of the purine hypoxanthine to xanthine and, in turn, into uric acid. Unlike rasburicase, allopurinol reduces uric acid formation, but does not lower serum uric acid levels.

Treatment of tumour lysis includes:

• Rasburicase 0.2 mg/kg
• Aggressive fluid resuscitation
• Correction of electrolyte abnormalities
  • Hyperkalaemia – requires most rapid correction due to the risk of cardiac dysrhythmia. Continuous cardiac monitoring should be employed. Calcium gluconate can be used temporarily to stabilise the myocardium, however, the lowest effective dose should be used (see below). Correction with insulin-dextrose can be employed, but potassium-lowering agents may also be required (e.g. patiromer)
  • Hyperphosphataemia – may be corrected with intravenous fluids and phosphate binders
  • Hypocalcaemia – calcium levels should be corrected cautiously until serum phosphate levels have been adequately corrected. This is due to the risk of calcium phosphate deposition. Calcium should be replaced to correct symptoms of hypocalcaemia including dysrhythmia and tetany.
• Renal replacement therapy – may be necessitated if measures including rasburicase and fluids are insufficient. Indications include anuria, refractory pulmonary oedema, and hyperkalaemia.