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 the use of rasburicase, which affects a rapid and complete degradation of uric acid to allantoin, potentially allowing a prompt continuation of chemotherapy 1. Prevention is key and includes aggressive hydration with intravenous fluids to maintain high urine output, allopurinol for moderate-risk patients, or rasburicase for high-risk patients or those with established hyperuricemia.
Pathophysiology and Risk Factors
TLS typically occurs after initiation of chemotherapy for highly proliferative malignancies such as high-grade lymphomas, acute leukemias, and some solid tumors with large tumor burden. 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 1.
Management and Treatment
Laboratory monitoring should be performed every 4-6 hours for the first 24-48 hours of treatment in high-risk patients, checking electrolytes, uric acid, creatinine, and phosphorus. Management of established TLS includes continued hydration, correction of electrolyte abnormalities (particularly hyperkalemia, hyperphosphatemia, and hypocalcemia), and sometimes renal replacement therapy for severe cases with acute kidney injury or refractory electrolyte disturbances. Rasburicase has been shown to be effective in reducing uric acid levels and is recommended for high-risk patients or those with established hyperuricemia 1.
Key Recommendations
- Aggressive hydration with intravenous fluids to maintain high urine output
- Rasburicase for high-risk patients or those with established hyperuricemia
- Allopurinol for moderate-risk patients
- Laboratory monitoring every 4-6 hours for the first 24-48 hours of treatment in high-risk patients
- Correction of electrolyte abnormalities and renal replacement therapy as needed.
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 cancer, particularly those with leukemia, lymphoma, or solid tumor malignancies.
- Definition: TLS is characterized by changes in laboratory parameters such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, as well as clinical events like renal failure, need for dialysis, arrhythmia, or seizure.
- Incidence: According to the study, clinical TLS occurred in 3% of patients treated with rasburicase (Elitek), 3% of patients treated with a combination of rasburicase and allopurinol, and 4% of patients treated with allopurinol alone 2.
- Management: The management of TLS involves the use of medications like rasburicase (Elitek) and allopurinol to reduce uric acid levels, as well as supportive care measures like hydration and monitoring of laboratory parameters.
- Key Considerations: It is essential to monitor patients at risk of TLS closely and initiate treatment promptly to prevent complications. The choice of treatment depends on the individual patient's needs and the severity of the condition. 2 3
From the Research
Definition and Pathogenesis of Tumor Lysis Syndrome
- Tumor lysis syndrome (TLS) is an acute, life-threatening disease associated with the initiation of cytoreductive therapy in the treatment of malignancy 4.
- It occurs when the destruction of tumor cells releases breakdown products that overwhelm the excretory mechanisms of the body 5.
- The syndrome results from the destruction (or lysis) of a large number of rapidly dividing malignant cells spontaneously or during chemotherapy 6.
Clinical Findings and Metabolic Derangements
- Characteristic findings include hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and uremia 4.
- Hyperuricemia can lead to uric acid nephropathy 5.
- Hyperphosphatemia and secondary hypocalcemia are also common findings 5.
- Clinical presentation is characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia 7.
Management and Treatment Options
- Conventional management of TLS consists of aggressive intravenous hydration, diuretic therapy, urinary alkalization, and inhibition of urate production by high-dose allopurinol 5.
- Urate oxidase has been used in the management of patients at risk for TLS, and recently the recombinant urate oxidase rasburicase was developed 5.
- Treatment options for hyperkalemia include sodium polystyrene sulfonate, hypertonic glucose and insulin, loop diuretics, and bicarbonate 5.
- Hemodialysis should be considered for every patient with excessively elevated uric acid, phosphate and/or potassium and in those patients with acute renal failure to control urinary volume and manage uremia 5.
- Management includes intravenous hydration to maintain urine flow, medications targeting hyperuricemia including rasburicase and allopurinol, and in severe cases renal replacement therapy may be required 7.
Risk Assessment and Prevention
- Risk assessment and prevention are at the forefront of management and rely on clinician awareness, prophylactic measures, and vigilant laboratory monitoring 4.
- Predisposing factors such as type of malignancy, chemotherapy regimen, and age are useful tools for inducing TLS suspicion 8.
- Established TLS requires early, aggressive intervention with intravenous hydration, electrolyte management, and the use of hypouricemic agents 4.