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When a fast-growing cancer such as some leukaemias and lymphomas is first treated, many cancer cells can die at once and flood the blood with potassium, phosphate and uric acid, which can damage the kidneys and heart. Teams check who is at risk, give extra fluids and a medicine (allopurinol, or rasburicase for higher risk) before treatment, and check blood tests often in the first days.
TLS is laboratory (two or more of raised uric acid, potassium or phosphate, or low calcium, by 25% from baseline or past fixed thresholds, from three days before to seven days after starting treatment) or clinical (laboratory TLS with renal failure, arrhythmia or seizure) (Italian consensus 2008). Risk rises with bulky or highly chemosensitive disease (Burkitt and lymphoblastic lymphoma, acute lymphoblastic leukaemia, bulky small cell lung cancer), LDH over twice normal, pre-existing renal impairment, dehydration and high uric acid. The Cairo 2010 expert panel assigns low, intermediate and high risk with a decision tree.
Prevention (Cairo 2008): close monitoring for low risk, hydration with allopurinol or rasburicase for intermediate risk, hydration with prophylactic rasburicase for high risk. The Italian consensus gives low-risk patients oral allopurinol and hydration and high-risk patients rasburicase 0.20 mg/kg/day over 30 minutes as inpatients, starting at least 4 hours before treatment and continuing 3 to 5 days, without allopurinol at the same time; rasburicase is contraindicated in G6PD deficiency and methaemoglobinaemia. Hydration ideally starts 48 hours ahead, keeping urine output at least 100 mL an hour in adults. Monitor LDH, uric acid, sodium, potassium, creatinine, urea, phosphate and calcium every 12 hours for 3 days in high-risk patients.
Established TLS: hydration and rasburicase, observations and electrolytes every 6 hours for the first 24 hours, calcium only for symptomatic hypocalcaemia, and renal replacement for persistent hyperkalaemia, severe acidosis, refractory overload or uraemia. Cairo 2008 does not recommend urine alkalinisation; the Italian consensus keeps it only for low-risk patients and those who cannot have rasburicase. The BSH 2015 guideline could not be read.
Why: Prevention is matched to risk; the highest-risk patients need inpatient care and rasburicase.
“Patients at high risk of developing TLS carry at least one of the following factors: (i) Host-related factors (comorbidities): dehydration; hyponatremia (limited to solid tumors); pre-existing renal impairment (including renal infiltration by hematologic malignancies which induce a reduction in renal function); obstructive uropathy; hyperuricemia (uric acid >8 mg/dL in children and >10 mg/dL in adults).”
Why: The cheaper drug is enough when risk is lower; rasburicase removes existing uric acid quickly when it is high.
“Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients.”
Why: Good urine flow washes out uric acid, potassium and phosphate before they build up.
“When possible, hydration should start at least 48 hours before tumor-specific therapy; however, the use of rasburicase with subsequent rapid degradation of uric acid allows earlier administration of chemotherapy, if needed.”
Why: Rasburicase breaks down uric acid already in the blood; allopurinol only stops new uric acid forming.
“Rasburicase should be administered at the dose of 0.20 mg/kg/day, infused over 30 minutes, administering the first dose at least four hours before the start of tumor-specific therapy and continuing for at least 3-5 days.”
Why: Allopurinol causes xanthine to build up and starves rasburicase of uric acid to act on.
“In order to avoid xanthine accumulation and lack of substrate for rasburicase, concomitant allopurinol should not be administered.”
Why: Rasburicase can cause severe haemolysis and methaemoglobinaemia in these patients.
“Rasburicase is contraindicated in patients with metahemoglobinemia, G6PDH deficiency or other metabolic disorders that can potentially cause hemolytic anemia; these patents should be treated with oral allopurinol, hydration and urine alkalinization.”
Why: TLS usually develops within the first days of treatment, and early changes can be corrected before harm.
“In patients at high risk of TLS, levels of LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus and calcium should be monitored every 12 hours for the first three days, and every 24 hours subsequently.”
Why: A shared definition triggers treatment at the same point everywhere.
“Clinical TLS is defined by the presence of laboratory TLS and at least one of the following clinical alterations: renal failure (estimated glomerular filtration rate ≤ 60 mL/min), cardiac arrhythmia, seizure.”
Why: Clearing uric acid quickly protects the kidneys and lets cancer treatment continue.
“Hydration through a central venous access and rasburicase should be administrated to all patients with clinical TLS.”
Why: Calcium given when phosphate is high can deposit as crystals in the kidneys and tissues.
“Asymptomatic hypocalcemia does not require treatment.”
Why: Dialysis removes potassium, phosphate and uric acid when the kidneys cannot.
“Indications for the start-up of renal replacement therapy in TLS include persistent hyperkalemia, severe metabolic acidosis, volume overload unresponsive to diuretic therapy, and overt uremic symptoms, including pericarditis and severe encephalopathy.”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
Risk-adapted prophylaxis is common ground: hydration for everyone at risk, allopurinol at lower risk and rasburicase at high risk, given before treatment starts (Cairo 2008; Cairo 2010 risk model; Italian consensus 2008). The sources disagree on urine alkalinisation: Cairo 2008 does not recommend it, while the Italian consensus still lists it for low-risk patients and for those who cannot have rasburicase, although it also says alkalinisation brings no biochemical advantage and has been progressively abandoned. Rasburicase dosing and schedule here are from the Italian consensus (0.20 mg/kg/day for 3 to 5 days); lower and single fixed doses are in use but were described as under evaluation in 2008. The UK guideline (BSH 2015), the most recent national guideline in the census, could not be read, so this page does not say how the UK position differs.
Journal of Clinical Oncology (expert panel) 2008 · British Journal of Haematology (international expert panel) 2010 · Italian Society of Hematology (SIE), Italian Association of Pediatric Oncologists (AIEOP) and Italian Society of Medical Oncology (AIOM), Haematologica 2008 · British Society for Haematology, British Journal of Haematology 2015
Where it differs: States that alkalinisation is not recommended for prevention or treatment.
Evidence: Expert panel evidence-based review (abstract read).
Where it differs: Gives low-risk children and adults oral allopurinol, hydration and urine alkalinisation, and uses alkalinisation for those who cannot have rasburicase.
Evidence: Consensus conference endorsed by SIE, AIEOP and AIOM; the same document says alkalinisation does not improve the biochemistry of TLS.
Where it differs: Stratifies TLS risk before a five-week ramp-up of venetoclax (20, 50, 100, 200, 400 mg), starts allopurinol two to three days ahead and oral fluids of 1.5 to 2 litres a day for the two days before, admits high-risk patients for intravenous fluids, and checks blood chemistry before, and 8 and 24 hours after, each dose increase. The author gives the first dose early in the morning so the 6 to 8 hour blood test is seen while staff are present.
Evidence: A single clinician's practical review following the product label; medical writing support was funded by the manufacturer.
Where it differs: Monitors disease burden and potassium, phosphate, calcium, uric acid and creatinine, gives allopurinol as prophylaxis before CAR T cells, and considers rasburicase for established TLS.
Evidence: LE: 3 for monitoring, LE: 4 for allopurinol and rasburicase.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Risk-adapted prophylaxis: rasburicase for high risk, allopurinol or rasburicase for intermediate, monitoring for low | expert panel consensus (grades not in abstract) | Journal of Clinical Oncology (expert panel) 2008 |
| Alkalinisation not recommended “Alkalinization is not recommended.” | expert panel consensus (grades not in abstract) | Journal of Clinical Oncology (expert panel) 2008 |
| Hydration and rasburicase for high-risk adults; hydration and oral allopurinol for low risk | consensus conference recommendation (not graded) | Italian Society of Hematology (SIE), Italian Association of Pediatric Oncologists (AIEOP) and Italian Society of Medical Oncology (AIOM), Haematologica 2008 |
| Allopurinol before CAR T cells “For prophylaxis against TLS prior to CAR T cell therapy, allopurinol should be administered” | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2020 |
Shares the tags protocol, acute-oncology, oncological-emergency, metabolic.
Shares Allopurinol, Rasburicase, Tumour lysis syndrome (TLS).
Shares the tags protocol, acute-oncology, oncological-emergency.
Shares the tags protocol, acute-oncology, oncological-emergency.
Shares the tags protocol, acute-oncology, oncological-emergency.
Shares the tags protocol, acute-oncology, oncological-emergency.
Shares the tags protocol, acute-oncology, oncological-emergency.
Shares the tags protocol, acute-oncology, oncological-emergency.