What is 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 characterized by metabolic abnormalities that occur when large numbers of cancer cells die rapidly, releasing their contents into the bloodstream. This approach is supported by the guidelines for the management of pediatric and adult tumor lysis syndrome, which emphasize the importance of prevention and early recognition of the syndrome 1.

Prevention and Management

Prevention is key and includes aggressive hydration with intravenous fluids at 2-3 L/m²/day to maintain high urine output, along with allopurinol 300-600 mg daily for moderate-risk patients starting 24-48 hours before chemotherapy. For high-risk patients, rasburicase 0.1-0.2 mg/kg IV is preferred over allopurinol due to its rapid action in reducing uric acid levels 1. Laboratory monitoring should include electrolytes, uric acid, phosphate, calcium, and creatinine every 4-6 hours for the first 24-48 hours of treatment.

Risk Stratification

The guidelines recommend stratifying patients into high-, intermediate-, and low-risk categories, with high-risk patients requiring aggressive intervention, including rasburicase and intensive care unit admission 1. Intermediate-risk patients may be managed with allopurinol or a single dose of rasburicase, while low-risk patients can be monitored closely without prophylactic treatment.

Established TLS Management

Management of established TLS requires intensive care monitoring, continued aggressive hydration, correction of electrolyte abnormalities, and possible renal replacement therapy for severe cases with acute kidney injury, persistent hyperkalemia, or symptomatic hypocalcemia 1. Cardiac monitoring is essential due to the risk of arrhythmias from electrolyte disturbances. Early recognition and intervention are crucial as untreated TLS can rapidly progress to acute kidney injury, cardiac arrhythmias, seizures, and death.

Some key points to consider in the management of TLS include:

• Aggressive hydration to maintain high urine output
• Use of rasburicase for high-risk patients
• Laboratory monitoring every 4-6 hours for the first 24-48 hours of treatment
• Correction of electrolyte abnormalities
• Possible renal replacement therapy for severe cases
• Cardiac monitoring due to the risk of arrhythmias from electrolyte disturbances.

From the Research

Definition and Pathophysiology of Tumour Lysis Syndrome

• Tumour lysis syndrome (TLS) is an oncologic emergency that occurs after the treatment of a malignancy with chemotherapy and/or radiotherapy, resulting in extreme tumor cell lysis with the release of intracellular potassium, nucleic acids, and phosphorus into the systemic circulation 2.
• The metabolic disturbances of TLS include hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute renal failure 2, 3.

Risk Factors and Diagnosis

• TLS occurs most often after administration of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukemia, but it can also occur spontaneously in tumor types that have a high proliferative rate and/or a large tumor burden 2.
• The incidence of TLS appears to be increasing due to a rapidly growing armamentarium of highly effective biologic and targeted therapies 3.
• Diagnostic laboratory criteria for TLS include hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and uremia 3, 4.

Prevention and Management

• The most important treatment for TLS is prevention, which includes aggressive hydration, control of hyperuricemia with allopurinol and rasburicase treatment, and close monitoring of electrolyte abnormalities 2, 4.
• Established TLS requires early, aggressive intervention with intravenous hydration, electrolyte management, and the use of hypouricemic agents 3, 5.
• In severe cases, renal replacement therapy may be required 4.
• Risk assessment and prophylactic therapy are critical in preventing this oncological emergency 5.

Clinical Findings and Complications

• Characteristic findings of TLS include hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and uremia, all of which can lead to cardiac arrhythmia, seizures, renal failure, and sudden death 3.
• Acute kidney injury due to tumor lysis is potentiated by the precipitation of uric acid and calcium phosphate as well as renal vasoconstriction 4.