What are the prophylactic measures for Tumor Lysis Syndrome (TLS) in various types of malignancies (cancers)?

From the Guidelines

Tumor Lysis Syndrome Prophylaxis

Tumor lysis syndrome (TLS) prophylaxis is strongly recommended for patients with high-risk cancers, such as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Burkitt lymphoma, and other aggressive lymphomas, to prevent the onset of this potentially life-threatening condition 1.

Prophylactic Measures

For patients at high risk of TLS, prophylaxis with allopurinol 300 mg/m²/day or rasburicase 0.2 mg/kg/day is recommended, starting 24-48 hours before initiation of chemotherapy 1.

• Allopurinol can be continued for 7-10 days,
• while rasburicase is typically given for 1-3 days. Additionally, aggressive hydration with at least 2-3 liters of intravenous fluids per day is recommended to help prevent TLS 1.

Risk-Based Approach

• For patients with moderate risk of TLS, allopurinol 100-200 mg/m²/day or febuxostat 40-80 mg/day can be used, along with hydration.
• In patients with low risk of TLS, hydration and monitoring of uric acid and electrolyte levels may be sufficient.

Monitoring and Adjustment

It is essential to monitor patients closely for signs of TLS, including hyperuricemia, hyperphosphatemia, hypocalcemia, and acute kidney injury, and to adjust prophylaxis accordingly 1.

Key Considerations

• Rasburicase should be administered at the dose of 0.20 mg/kg/day, infused over 30 minutes, administering the first dose at least four hours before the start of tumor-specific therapy and continuing for at least 3-5 days 1.
• Allopurinol should be administered orally at the dose of 100 mg/m2 thrice daily (maximum 800 mg/day) 1.
• Concomitant allopurinol should not be administered with rasburicase to avoid xanthine accumulation and lack of substrate for rasburicase 1.

From the FDA Drug Label

A total of 342 adults with either leukemia, lymphoma, or other hematologic malignancy received Elitek in five studies (one randomized study, Study 4, and four uncontrolled studies). Patients were eligible for the study if they were either at high risk or potential risk for TLS. 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. 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.

The prophylactic measures for Tumor Lysis Syndrome (TLS) in various types of malignancies (cancers) include:

• Administration of rasburicase (Elitek) at a dose of 0.15 mg/kg/day or 0.2 mg/kg/day to reduce uric acid levels
• Use of allopurinol orally at a dose of 300 mg once a day as an alternative or in combination with Elitek
• Monitoring of uric acid levels and laboratory parameters for hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia
• Identification of patients at high risk or potential risk for TLS to initiate antihyperuricemic treatment 2 Key points:
• Elitek was effective in reducing uric acid levels and preventing clinical TLS
• Combination therapy with Elitek and allopurinol may be considered in some cases
• Monitoring of laboratory parameters is crucial to prevent and manage TLS 2

From the Research

Prophylactic Measures for Tumor Lysis Syndrome (TLS)

The prophylactic measures for TLS in various types of malignancies (cancers) include:

• Aggressive hydration to prevent dehydration and reduce the risk of acute renal failure 3, 4
• Urate-lowering therapy, such as allopurinol and rasburicase, to control hyperuricemia 5, 6, 4
• Avoidance of exogenous potassium to prevent hyperkalemia 3
• Use of phosphate binders to prevent hyperphosphatemia 3
• Vigilant laboratory and clinical monitoring to detect early signs of TLS 3, 4
• Cytoreduction before the start of aggressive chemotherapy or gradual escalation of chemotherapy dose in high-risk cases 3

Risk Factors for TLS

Patients with the following risk factors are at high risk for TLS:

• High-tumor burden hemato-oncologic malignancies, such as lymphoid malignancies and solid tumors with extensive metastases and organ or bone marrow involvement 7, 6
• Highly proliferative lymphoblastic lymphoma subtype or Burkitt lymphoma 5
• Increased level of serum creatinine, which may reduce the efficacy of single-dose rasburicase to prevent TLS 5

Management of TLS

The management of TLS includes:

• Early detection and treatment of TLS to prevent life-threatening complications, such as acute renal failure, cardiac dysrhythmia, and seizures 4
• Consideration of cytoreduction before the start of aggressive chemotherapy or gradual escalation of chemotherapy dose in high-risk cases 3
• Use of renal replacement therapy (RRT) in cases of hyperkalemia, severe hyperphosphatemia, or acidosis, and fluid overload unresponsive to diuretic therapy 3