Tumor Lysis Syndrome (TLS)

What happens in tumor lysis syndrome

Cancer cells contain large amounts of potassium, phosphate and nucleic acids (DNA and RNA). When many cells die at once, these are released into the bloodstream faster than the kidneys can clear them.

• High potassium (hyperkalemia): can cause muscle weakness and dangerous heart rhythms.
• High phosphate (hyperphosphatemia): binds calcium, causing low calcium and forming calcium phosphate crystals that block the kidneys.
• High uric acid (hyperuricemia): from breakdown of nucleic acids; uric acid crystals can also block kidney tubules.
• Low calcium (hypocalcemia): causes cramps, tingling, spasms, seizures and heart rhythm problems.

These changes together can cause acute kidney injury, which further reduces the body's ability to clear potassium and phosphate, creating a dangerous cycle.

Who is at risk

Risk depends on the cancer, its size and the treatment.

Cancer factors

• High risk: Burkitt lymphoma, acute lymphoblastic leukemia and acute myeloid leukemia with very high white cell counts, and other aggressive lymphomas
• Intermediate risk: other lymphomas, chronic lymphocytic leukemia treated with venetoclax or other potent targeted drugs, and some very bulky or chemotherapy-sensitive solid tumors
• Low risk: most solid tumors, multiple myeloma and slower-growing blood cancers

Patient factors

• Large tumor burden, high LDH or high white cell count
• Kidney disease, dehydration or low urine output before treatment
• High uric acid or potassium before treatment
• Medicines that affect the kidneys or raise potassium

Symptoms

Many changes are found on blood tests before symptoms appear. When symptoms occur, they reflect the chemical imbalances:

• Nausea, vomiting, diarrhea and loss of appetite
• Tiredness and weakness
• Reduced urine, dark or cloudy urine, swelling and breathlessness from fluid overload
• Muscle cramps, twitching, tingling around the mouth and in fingers
• Palpitations, irregular heartbeat, fainting
• Confusion, seizures
• Joint pain like gout from uric acid

Diagnosis: Cairo-Bishop criteria

Doctors commonly use the Cairo-Bishop criteria, applied from 3 days before to 7 days after starting treatment.

Laboratory TLS means at least two of these:

A 25% change from baseline in any of these also counts in the original criteria.

Clinical TLS means laboratory TLS plus at least one of:

• A rise in creatinine to 1.5 times the upper limit of normal or more (kidney injury)
• Heart rhythm disturbance or sudden death
• Seizure

Prevention

Prevention is planned before treatment starts, based on risk.

• IV fluids in generous volumes, adjusted to body size, to keep urine flowing well, with careful monitoring of fluid balance and weight.
• Allopurinol or febuxostat to reduce new uric acid production, started 1 to 2 days before treatment in intermediate risk.
• Rasburicase, an enzyme that rapidly breaks down existing uric acid, for high-risk patients. It must not be given to people with G6PD deficiency, because it can cause severe red cell breakdown, so G6PD is tested first when possible.
• Frequent blood tests, often every 6 to 12 hours in high-risk patients during the first days, and in hospital for some treatments.
• Gradual dose increase for venetoclax in CLL (the "ramp-up"), with lab checks at each step.
• Avoid potassium and phosphate supplements and kidney-harming drugs such as NSAIDs and IV contrast where possible.
• Pre-phase therapy in some lymphomas: a gentler first treatment to reduce tumor size slowly.

Treatment

TLS is managed in hospital, often in intensive care for clinical TLS.

• More IV fluids if the kidneys and heart can tolerate them
• Rasburicase for high uric acid
• High potassium: heart monitoring, IV calcium to protect the heart, insulin with glucose, and medicines that remove potassium
• High phosphate: phosphate binders and restricting phosphate intake
• Low calcium: treated with calcium only when it causes symptoms, because extra calcium with high phosphate can increase crystal deposits
• Dialysis for severe kidney injury, very high potassium or phosphate, or fluid overload. Kidney function often recovers.

Urine alkalinization with sodium bicarbonate is no longer routinely recommended.

Outlook

With modern prevention, serious TLS is much less common, and most patients complete cancer treatment safely. Clinical TLS carries significant risks, particularly from kidney failure and heart rhythm problems, but prompt treatment and dialysis when needed save lives, and kidney function often returns.

Frequently asked questions

What are the first signs of tumor lysis syndrome?

Early TLS is often found on blood tests before symptoms, as rising potassium, phosphate, uric acid or creatinine. The first symptoms can be nausea, vomiting, tiredness, reduced urine, muscle cramps or tingling. Palpitations, fainting or seizures signal more severe imbalances and need emergency care.

How soon after chemotherapy does tumor lysis syndrome happen?

It usually develops 12 to 72 hours after the first dose of chemotherapy, targeted therapy or radiation. With venetoclax for CLL, risk is highest around the first doses of each dose increase. Rarely, very fast-growing cancers cause spontaneous TLS before any treatment.

What are the Cairo-Bishop criteria?

They are the standard criteria for diagnosing tumor lysis syndrome. Laboratory TLS requires at least two abnormal values among uric acid, potassium, phosphate and calcium within a window around treatment. Clinical TLS adds kidney injury, a heart rhythm disturbance or a seizure.

Can tumor lysis syndrome be prevented?

Most cases can. People at risk receive IV fluids, allopurinol or rasburicase, and close blood monitoring in the first days of treatment. High-risk patients may be treated in hospital, start with lower doses, or have dialysis available. Drinking plenty of fluids as instructed also helps.

Is tumor lysis syndrome a good sign that treatment is working?

It shows that the cancer cells are being killed quickly, which can mean the cancer is very sensitive to treatment. But TLS itself is dangerous, not a measure of a cure. The goal is to kill cancer cells while preventing TLS through careful planning and monitoring.