Tumor lysis syndrome

Definition

Tumor lysis syndrome (TLS) is a metabolic derangement caused by the rapid breakdown of large numbers of tumor cells. The released intracellular components lead to the typical constellation of hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia. Uric acid arises from the breakdown of released nucleic acids. Uric acid and calcium phosphate can precipitate in the renal tubules and cause acute kidney injury; calcium phosphate can also deposit in the cardiac conduction system.

TLS usually occurs within a few days after cytotoxic drugs are started, less often spontaneously before any anticancer measures. Rapidly growing, bulky hematologic neoplasms such as aggressive non-Hodgkin lymphomas (particularly Burkitt lymphoma and diffuse large B-cell lymphoma), acute lymphoblastic and acute myeloid leukemia are most often affected; in solid tumors it is rare.

Clinical features

Symptoms reflect the metabolic disturbances:

• nausea, vomiting, diarrhea, anorexia, lethargy
• muscle pain and cramps, paresthesias
• Hypocalcemia: neuromuscular hyperexcitability with tetany, seizures, cardiac arrhythmias
• Hyperkalemia: muscle weakness up to paralysis, cardiac arrhythmias
• Acute kidney injury due to urate nephropathy and nephrocalcinosis, with oliguria
• syncope, in severe cases sudden cardiac death

Diagnosis

Diagnostic criteria

The Cairo-Bishop criteria (2004), modified in 2011 by Howard and colleagues, are commonly used:

• Laboratory TLS: at least two of the following abnormalities within 3 days before to 7 days after the start of cytotoxic drugs: uric acid ≥ 476 µmol/L (8 mg/dL), potassium ≥ 6 mmol/L, phosphate ≥ 1.45 mmol/L (adults), calcium ≤ 1.75 mmol/L, or a 25 % change of the respective value from baseline.
• Clinical TLS: laboratory TLS plus at least one organ manifestation: creatinine increase to > 1.5 times normal, cardiac arrhythmia or sudden death, seizure.
• According to Howard, the laboratory abnormalities count only if they occur together within 24 hours; a mere 25 % change from baseline is no longer sufficient, and symptomatic hypocalcemia always counts as a criterion of clinical TLS.

Investigations

• Laboratory tests: potassium, phosphate, calcium, uric acid, creatinine, and urea; LDH as a marker of high cell turnover; complete blood count with white cell count.
• Findings with increased TLS risk: high tumor burden (tumors > 10 cm), leukocytosis (> 25,000/µL), LDH > 2 times normal, preexisting renal insufficiency or elevated uric acid, hypovolemia.
• ECG: hyperkalemia and hypocalcemia can cause ECG changes and cardiac arrhythmias.
• Urine output to detect oliguria; other causes of acute kidney injury are to be distinguished.

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Further reading (open access)

1. Biomedicines 2022: Tumor Lysis Syndrome in Onco-Nephrology (PMC-Volltext)
2. J Community Hosp Intern Med Perspect 2020: Diagnosis of tumor lysis syndrome (PMC-Volltext)
3. Curr Oncol 2025: Tumorlysesyndrom bei AML unter Azacitidin–Venetoclax, Cairo-Bishop- und Howard-Kriterien (PMC-Volltext)

Cross-references