Tumour lysis syndrome: a cancer treatment emergency explained

When cancer cells die in large numbers, they release their contents into the blood. Macmillan explains that venetoclax, for example, can cause leukaemia or cancer cells to break down very quickly, releasing a waste product called uric acid into the blood. The kidneys usually get rid of uric acid but may not cope with large amounts, and this can cause tumour lysis syndrome.

The NHS Lothian acute oncology guideline defines TLS as a life-threatening complication of malignancies and systemic anticancer therapy, characterised by hyperuricaemia (high uric acid), hyperkalaemia (high potassium), hyperphosphataemia (high phosphate), hypocalcaemia (low calcium) and oliguric renal failure (kidney failure with low urine output). It may occur before, or more commonly soon after, systemic anticancer therapy.

The guideline distinguishes laboratory TLS, where blood tests show metabolic abnormalities alone, from clinical TLS, where there are also problems such as a raised creatinine (a marker of kidney function), a cardiac arrhythmia, a seizure or sudden death. It uses the Cairo-Bishop definition for this, which is a clinical classification used by teams rather than something people need to apply themselves.

Macmillan says some people are at risk of developing TLS, and that the risk is highest at the beginning of treatment. The NHS Lothian guideline lists patients considered high risk, including those with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) with a high white cell count, AML treated with azacitidine and venetoclax, Burkitt lymphoma, lymphoblastic lymphoma, stage III or IV non-Hodgkin lymphoma with a high LDH or large tumour bulk on CT scan, and chronic lymphocytic leukaemia (CLL) with high tumour burden starting venetoclax. It says that rarely, other conditions such as chronic myeloid leukaemia in blast crisis may need prophylaxis.

It lists moderate risk groups, such as CLL patients on venetoclax dose increments, lymphoma patients not meeting high-risk criteria, patients with high-bulk haematological malignancies and those with a past or current history of gout. Factors that make rasburicase indicated in high-risk patients include pre-existing high uric acid, difficulty with fluid balance preventing adequate hydration, allergy to allopurinol, and impaired kidney function. The decision about risk is made by the oncology or haematology team on individual blood results and scans.

The pages read for this guide describe TLS mainly through blood results and complications, not a list of symptoms. The Lothian guideline names cardiac arrhythmia, seizure and sudden death as features of clinical TLS and a raised creatinine as a marker of kidney injury, and Macmillan says it can affect the kidneys and heart. That is why monitoring is done with blood tests rather than relying on how a person feels.

The practical advice from Macmillan is to follow the instructions you are given and to contact the hospital on the 24-hour contact number for advice if you are unwell during treatment, for example if you are sick just after taking venetoclax. If you are on a treatment known to carry TLS risk, keep the 24-hour number to hand and ask the team what symptoms they want you to report.

Prevention has three strands. The first is fluid. Macmillan says people are advised to drink plenty of water before and when they start venetoclax, with at least 2 litres (3½ pints) of fluid a day helping. The NHS Lothian guideline says patients at moderate risk should be able to drink a minimum of 2 litres of fluid (not including tea or coffee) daily, and that intravenous fluids can be given if they cannot, or if they are at high risk.

The second is medicines that lower uric acid. Macmillan names allopurinol tablets and rasburicase through a drip. The Lothian guideline explains that allopurinol prevents the production of uric acid and may take several days to normalise the level, whereas rasburicase rapidly converts uric acid into an inactive, soluble substance that the kidney can excrete. It adds that rasburicase should not be used in people with G6PD deficiency, which is why screening is advised for at-risk patients, and that adding allopurinol is unnecessary when rasburicase is being used.

The third is monitoring with regular blood tests. Macmillan says you will have regular blood tests to check uric acid levels and make sure the kidneys are working well, and the Lothian guideline describes repeated measurements of urate, kidney function, electrolytes, calcium and phosphate until the levels are normal and the risk has passed. Macmillan also describes venetoclax being started at a low dose that is gradually increased, in its section on reducing the risk of TLS.

The Lothian guideline says that if TLS occurs despite prophylaxis, rasburicase is given at a treatment dose, with intravenous fluids, fluid balance charts, twice-daily weights and furosemide as appropriate for fluid overload. Blood tests are repeated every few hours until parameters have normalised, and dialysis is considered if clinical and biochemical parameters do not improve with these measures. The case is discussed with a consultant.

This is hospital treatment. It is not something that can be managed at home, and the pages read for this guide describe it in terms for clinicians, so the details of doses are not repeated here.

Knowing about TLS can make the first weeks of a cancer treatment less daunting. It is expected by the team, and the arrangements for fluids, tablets, blood tests and possibly a short admission exist because it can be prevented or treated, as Macmillan says. Macmillan also notes that during treatment with venetoclax, grapefruit, star fruit and Seville oranges should be avoided because they can affect how it works and make side effects worse, and that tablets should be taken exactly as instructed.

If you take any other medicines, supplements or herbal remedies, tell the cancer doctor, nurse or pharmacist, as Macmillan advises. Keep a record of your fluid intake in the early days if the team asks you to.

Patient-facing UK information specifically about TLS was limited. This page relies on a Macmillan treatment page for venetoclax and on an NHS Lothian acute oncology guideline written for clinicians, so some of the detail will reflect one health board's protocol rather than national policy. Ask your own team about local arrangements.

On the NHS, TLS is prevented and treated by oncology and haematology teams, with acute oncology services responding to emergencies. Private cancer treatment follows the same principles, with the same need for hydration, blood tests and rapid access to hospital care. Whoever delivers the treatment should give you a 24-hour contact number and an explanation of what to do if you become unwell.