From the Guidelines
Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic emergency that requires immediate attention, and the first-line treatment to prevent it is aggressive hydration with intravenous fluids and rasburicase prophylaxis in high-risk patients, as recommended by the most recent guidelines 1.
Definition and Pathophysiology of TLS
Tumor lysis syndrome occurs when large numbers of cancer cells die rapidly, releasing their contents into the bloodstream, typically after initiating chemotherapy for cancers with high cell turnover rates, such as high-grade lymphomas and leukemias. This leads to hyperuricemia, electrolyte disturbances, renal failure, and overt organ damage.
Prevention and Treatment of TLS
The first-line treatment to prevent TLS is aggressive hydration with intravenous fluids (typically isotonic saline at 3 L/m2 per day), which should be started 24-48 hours before chemotherapy, unless there is evidence of renal insufficiency and oliguria 1.
- Rasburicase prophylaxis is recommended for patients with a high risk of developing TLS (WBC >100 × 109/L, high tumor burden) 1.
- Urinary alkalinization is no longer recommended 1.
- Allopurinol (300-600 mg daily) may be used as an alternative to rasburicase, but it is not preferred for high-risk patients due to its slower onset of action and potential for xanthine accumulation 1.
- Electrolyte abnormalities should be corrected before starting therapy, and frequent monitoring of electrolytes (potassium, phosphorus, calcium) and renal function is essential during treatment.
- Diuretics should be avoided initially as they may concentrate urine and promote crystal formation.
- Intractable fluid overload, hyperkalemia, hyperuricemia, hyperphosphatemia, or hypocalcemia are indications for renal dialysis 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.
The major endpoint of this study was the uric acid response rate defined as the proportion of patients with plasma uric acid levels ≤7.5 mg/dL from day 3 to day 7, after initiation of antihyperuricemic treatment.
Table 2 presents the response rates in the three treatment arms. The response rate in arm A was significantly greater than in arm C (p=0.0009).
Tumor Lysis Syndrome (TLS) is a condition characterized by changes in laboratory parameters such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, along with events like renal failure, need for renal dialysis, or serum creatinine increase.
The first-line treatment to prevent TLS is rasburicase (Elitek), which is administered at a dose of 0.2 mg/kg/day as a 30-minute infusion once daily, as it has been shown to have a higher response rate in controlling uric acid levels compared to allopurinol alone 2.
From the Research
Definition of Tumor Lysis Syndrome
- Tumor lysis syndrome (TLS) is an oncologic emergency that typically occurs after the treatment of a malignancy with chemotherapy and/or radiotherapy, resulting from extreme tumor cell lysis with the release of intracellular potassium, nucleic acids, and phosphorus into the systemic circulation 3, 4, 5, 6.
- It can also occur spontaneously in tumor types that have a high proliferative rate and/or a large tumor burden 3.
Metabolic Disturbances of TLS
- The metabolic disturbances of TLS include hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute renal failure 3, 4, 5, 6.
- These disturbances can lead to life-threatening complications such as acute renal failure, cardiac dysrhythmia, and seizures 3, 6.
Prevention and Treatment of TLS
- 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 3, 5, 7.
- Established TLS requires early, aggressive intervention with intravenous hydration, electrolyte management, and the use of hypouricemic agents 6.
- Rasburicase is a highly effective agent for reducing serum uric acid levels and can be used in patients with renal dysfunction, significant elevations in serum uric acid values, or large tumor burdens 7.