Emergent Care / Stabilization:
The acute electrolyte and metabolic disturbances of tumor lysis syndrome can cause life-threatening cardiac arrhythmias, seizures, renal insufficiency / acute failure, and multisystem organ failure. Prompt management of hyperkalemia, hypocalcemia, hyperphosphatemia, and hyperuricemia are paramount.

Diagnosis Overview:
Tumor lysis syndrome (TLS) is a life-threatening condition that occurs primarily in hematologic cancers (leukemias and lymphomas), but it may be seen with other tumors in which tumor cells lyse, releasing intracellular contents and causing severe electrolyte and metabolic disturbances. Classically, patients will display hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia that can lead to cardiac arrythmias, seizures, renal damage, and multisystem organ failure.

TLS is diagnosed based on a combination of laboratory and clinic criteria according to the system proposed by Cairo and Bishop. To make a diagnosis of TLS, 2 laboratory criteria (L-TLS) and 1 clinical criterion (C-TLS) must be present in a 24-hour period occurring 3 days before the start of therapy until 7 days after initiation of therapy.

Laboratory criteria (L-TLS) including 2 or more of the following:

• Potassium – 25% increase from baseline or > 6 mmol/L
• Phosphorus – 25% increase from baseline or
  • > 4.5 mg/dL in adults
  • > 6.5 mg/dL in children
• Uric acid – 25% increase from baseline or
  • > 8 mg/dL in adults
  • > Upper limit for children by age
• Corrected calcium – 25% decrease from baseline or < 7 mg/dL

AND

Clinical criteria (C-TLS) including 1 or more of the following:

• Cardiac dysrhythmia or sudden death
• ECG signs of hyperkalemia
• Seizure, or neuromuscular irritability
• Acute kidney injury – oliguria or increased (1.5 times the upper limit for age, or more) creatinine (from baseline)

The Howard criteria modified the Cairo-Bishop criteria to remove the 25% increase from baseline criteria for the electrolytes and to add an increase of 0.3 mg/dL above baseline for serum creatinine for L-TLS criteria.

Risk factors for TLS include cancers with greater mass or increased cellularity, rapidly proliferating tumors, and high sensitivity to cytotoxic chemotherapy, as well as preexisting renal insufficiency, dehydration, and hypotension.

While classically seen in hematologic malignancies, TLS now occurs with other tumor types due to more effective targeted anticancer drugs.

TLS may be prevented with aggressive intravenous (IV) hydration with careful monitoring of urine output, renal function, cardiac function, and electrolytes. Alkalinization of the urine remains controversial. A hypouricemic agent, such as allopurinol, rasburicase, and febuxostat, can be used as a preventive agent in TLS. Despite preventive measures, 3%-5% of patients with leukemia / lymphoma will develop TLS.

Treatment of TLS involves very careful laboratory and clinical monitoring with prompt treatment of electrolyte and metabolic disturbances.