What is the diagnosis and management of Tumor Lysis Syndrome (TLS)?

From the Guidelines

Tumor lysis syndrome (TLS) should be managed with aggressive hydration and rasburicase for high-risk patients, as it is a potentially life-threatening oncologic emergency that requires prompt recognition and treatment. The management of TLS involves prevention with aggressive hydration using intravenous fluids at 2-3 L/m²/day to maintain high urine output, along with allopurinol 300-600 mg daily for moderate-risk patients 1. For high-risk patients, rasburicase 0.1-0.2 mg/kg IV is preferred over allopurinol, as it has been shown to be effective in preventing and treating TLS 1.

Key Considerations

• Hydration should be administered through a central venous access, and urine output should be kept at least at 100 ml/hour (3 mL/kg/hour in children <10 kg body weight) 1.
• Rasburicase should be administered to all patients with clinical TLS, as well as to adults with laboratory TLS, children with high risk of TLS, or children with a rapid worsening of biochemical parameters of TLS 1.
• Laboratory monitoring should occur every 4-6 hours for the first 24-48 hours of treatment, focusing on potassium, phosphorus, calcium, uric acid, and creatinine levels 1.
• Established TLS requires intensive care management with correction of electrolyte abnormalities (hyperkalemia, hyperphosphatemia, hypocalcemia), management of acute kidney injury, and possibly renal replacement therapy for severe cases 1.

Treatment Approach

• For pediatric patients, rasburicase should be used in the initial management of high-risk patients, along with hydration and close monitoring in an intensive care unit or similarly monitored nursing area 1.
• For intermediate-risk pediatric patients, allopurinol may be used as an initial antihyperuricemic treatment, or a single dose of rasburicase might be considered 1.
• For pediatric patients unlikely to develop TLS, a watch-and-wait approach with close monitoring is entirely appropriate 1.

Pathophysiology

The pathophysiology of TLS involves massive tumor cell lysis causing release of intracellular contents (potassium, phosphate, nucleic acids) that overwhelm the body's excretory mechanisms, leading to metabolic derangements and potential organ failure, particularly affecting the kidneys through uric acid crystal formation and calcium phosphate precipitation 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. Clinical TLS occurred in 3% of Elitek-treated patients, 3% of Elitek/allopurinol-treated patients, and 4% of allopurinol-treated patients.

Tumor Lysis Syndrome (TLS) is a potentially life-threatening condition that can occur in patients with hematologic malignancies.

• Clinical TLS was observed in 3% of patients treated with Elitek (rasburicase), 3% of patients treated with Elitek/allopurinol, and 4% of patients treated with allopurinol alone 2.
• The definition of Clinical TLS includes changes in laboratory parameters such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, as well as events like renal failure, need for renal dialysis, arrhythmia, or seizure.
• Elitek (rasburicase) is used to manage plasma uric acid levels in patients at risk for TLS.
• The response rate to Elitek treatment was significantly higher compared to allopurinol alone 2.

From the Research

Definition and Pathogenesis of Tumor Lysis Syndrome

• Tumor lysis syndrome (TLS) is a rare but potentially life-threatening complication of neoplasms, preferentially hematological malignancies 3.
• It is characterized by a massive release of intracellular contents into the systemic circulation, leading to metabolic derangements such as hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and uremia 4.
• The incidence of TLS appears to be increasing due to the growing use of highly effective biologic and targeted therapies 4.

Risk Factors and Prevention

• Predisposing factors for TLS include the type of malignancy, chemotherapy regimen, and age 3.
• Close monitoring and hydration are essential to prevent TLS, particularly in patients with a large cancer cell mass 5.
• Intervention can include rasburicase and allopurinol, with the choice of treatment depending on the risk of TLS and the patient's individual needs 5, 6, 7.

Management and Treatment

• Management of TLS requires hydration, fluid balance, electrolytes and hyperuricemia correction, and ultimately dialysis when acute kidney injury is worsening 3.
• Rasburicase has been shown to be effective in reducing uric acid and preventing uric acid accumulation in patients with hematologic malignancies 6.
• Allopurinol is also used to manage hyperuricemia, but it can induce accumulation of xanthine or hypoxanthine, whereas rasburicase does not 6.
• The use of i.v. allopurinol and rasburicase can offer additional flexibility in the management of TLS and may allow for further avoidance of the consequences of inadequate management of this syndrome 7.