29th December 2024

Tumour lysis syndrome (TLS)

Overview of TLS

TLS is a syndrome characterised by biochemical and metabolic derangement driven by the rapid breakdown of tumour cells, causing the release of intracellular contents into the circulatory system. It is typically triggered by delivery of chemotherapy, however may also occur after any systemic anti-cancer treatment (SACT), after radiotherapy in radio-sensitive tumours, and even spontaneously in patients with a large tumour burden.

This is an emergency presentation, as the resultant renal impairment and electrolyte abnormalities can limit treatment options and can even result in death. It is crucial to identify TLS early, so that emergency treatment can be initiated, and also to identify patients at risk who may need prophylactic treatment and close monitoring.

Definition of TLS

TLS must be diagnosed through biochemical tests. It can be classified as laboratory or clinical TLS:

Risk factors for TLS

Risk stratifying allows the treating team to choose which patients to monitor closely or to offer prophylactic therapy.

Tumour type risk factors

TLS is generally associated with highly proliferative, chemosensitive cancers with a high burden of disease. It typically occurs in haematological malignancies, including ALL, AML, non-Hodgkin’s and Burkitt’s lymphoma. However, it can also occur in any solid tumour that has these risk factors, for example small cell lung cancer, breast cancer, renal cell cancer and metastatic testicular or germ cell cancers.

As options for SACT become more sophisticated and effective, the rates of TLS are likely to rise.

Patient risk factors

Patients with baseline biochemical abnormalities including high urate levels and chronic kidney disease are at higher risk of TLS. For the latter reason, the risk of TLS increases with age (thought to be due to worsening GFR). Exposure to nephrotoxic drugs may also increase the risk of TLS. Poor hydration status is also a risk factor, and some patients may require IV rehydration prior to commencing SACT.

Presentation of TLS

Management of TLS

TLS prophylaxis

When planning chemotherapy, it is important to consider strategies to prevent TLS in high risk patients.

All patients receiving chemotherapy should be monitored for biochemical and clinical features of TLS. Where possible, nephrotoxic drugs (such as NSAIDs and aminoglycosides) should be avoided, as well as drugs such as thiazide diuretics that increase serum uric acid levels.

In patients at high risk of TLS, there are a number of steps that may prevent TLS from developing.

1. IV hydration prior to treatment.
2. Phosphate binder to reduce serum phosphate levels, e.g. aluminium hydroxide, which binds and reduces bowel absorption of phosphate. Magnesium hydroxide is given to reduce the side effects of constipation.
3. Reduce serum uric acid levels:
   • Lower risk: allopurinol, a xanthine oxidase inhibitor, which reduces conversion of purine to uric acid. Will not reduce uric acid that has already been released by cells.
   • Higher risk: rasburicase, a recombinant urate oxidase enzyme, which converts uric acid into water-soluble allantoin, which prevents crystallisation and is more easily removed by the kidney. Contraindicated in patients with G6PD deficiency, haemolytic anaemia, methaemoglobinaemia.

Management of acute TLS

Acute TLS is an emergency and requires urgent action and close monitoring. Emergency management is as follows:

References

• Cassidy J, Bissett D, Spence RAJ, Payne M, Morris-Stiff GJ. Oxford Handbook of Oncology. 4th ed. Oxford: Oxford University Press; 2015
• Mughal T. Tumour lysis syndrome [Internet]. BMJ Best Practice. 2022 [cited 2022 Apr 17]. Available from: https://bestpractice.bmj.com/topics/en-gb/936
• Howard SC, Jones DP, Pui C-H. The Tumor Lysis Syndrome. The New England journal of medicine [Internet]. 2011 May 12;364(19):1844–54. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437249/