What is Tumor Lysis Syndrome (TLS)?

From the Guidelines

Tumor Lysis Syndrome (TLS) is a life-threatening complication characterized by a group of metabolic derangements caused by the massive and abrupt release of cellular components into the blood after the rapid lysis of malignant cells, as described in the guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review published in the Journal of Clinical Oncology in 2008 1. The key features of TLS include:

• High potassium (hyperkalemia)
• High phosphate (hyperphosphatemia)
• Low calcium (hypocalcemia)
• High uric acid (hyperuricemia) These electrolyte imbalances can lead to serious complications such as kidney failure, cardiac arrhythmias, seizures, and even death if not promptly treated. To prevent and manage TLS, the following measures are recommended:
• Hydration: Aggressive intravenous fluids to promote urine output and excretion of metabolites
• Allopurinol: Start at 100-300 mg orally every 8 hours, 2-3 days before chemotherapy and continue for 5-7 days after
• Rasburicase: For high-risk patients or those with established TLS, give 0.1-0.2 mg/kg IV once daily for 1-5 days
• Electrolyte management: Correct imbalances as needed, avoiding potassium and calcium supplements unless critically low
• Monitoring: Frequent blood tests to track electrolytes, uric acid, and renal function
• Dialysis: Consider in severe cases with refractory electrolyte abnormalities or acute kidney injury Early recognition and aggressive management of TLS are crucial to prevent serious complications and improve outcomes in cancer patients undergoing treatment, as emphasized in the guidelines published in the Journal of Clinical Oncology in 2008 1. The release of intracellular metabolites, including nucleic acids, proteins, phosphorus, and potassium, can overwhelm normal homeostatic mechanisms, potentially leading to hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and uremia, highlighting the importance of prompt and effective management of TLS 1.

From the FDA Drug Label

Tumor Lysis Syndrome (TLS) Clinical TLS was defined by changes in at least two or more laboratory parameters for hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia and at least one of the following events occurring within 7 days of treatment: renal failure/injury, need for renal dialysis, and/or serum creatinine increase >1.5 ULN, arrhythmia or seizure.

Tumor Lysis Syndrome (TLS) is a condition characterized by:

• Changes in at least two or more laboratory parameters for:
  • Hyperuricemia
  • Hyperkalemia
  • Hyperphosphatemia
  • Hypocalcemia
• At least one of the following events occurring within 7 days of treatment:
  • Renal failure/injury
  • Need for renal dialysis
  • Serum creatinine increase >1.5 ULN
  • Arrhythmia
  • Seizure 2

From the Research

Definition and Characteristics of Tumor Lysis Syndrome (TLS)

• Tumor Lysis Syndrome (TLS) is an acute, life-threatening disease associated with the initiation of cytoreductive therapy in the treatment of malignancy 3.
• It is caused by rapid tumor cell destruction and the resulting nucleic acid degradation during or days after initiation of cytotoxic therapy, and can also occur spontaneously 4.
• Characteristic findings include hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and uremia, which can lead to cardiac arrhythmia, seizures, renal failure, and sudden death 3, 4, 5, 6, 7.

Clinical Manifestations and Complications

• The metabolic abnormalities associated with TLS can lead to life-threatening complications, such as heart rhythm abnormalities and neurologic manifestations 4.
• Hyperkalemia is a hazardous acute complication that can cause sudden death from cardiac arrhythmias, and should be treated quickly and aggressively 4.
• Treatment of hypocalcemia is reserved for patients with electrocardiographic changes or symptoms of neuromuscular irritability 4.
• Acute kidney injury is a common complication of TLS, and may require renal replacement therapy 4, 5.

Management and Prevention

• Risk assessment and prevention are at the forefront of management, and rely on clinician awareness, prophylactic measures, and vigilant laboratory monitoring 3.
• Established TLS requires early, aggressive intervention with intravenous hydration, electrolyte management, and the use of hypouricemic agents 3, 4.
• Early detection of TLS is of vital importance, and can be accomplished by identification of high-risk patients, implementation of suitable prophylactic measures, and monitoring of electrolyte levels in patients undergoing chemotherapy 7.