What are the prophylactic measures for tumor lysis syndrome (TLS) in patients with diffuse large B cell lymphoma (DLBCL)?

From the Guidelines

Tumor Lysis Syndrome Prophylaxis in DLBCL Patients

Tumor lysis syndrome (TLS) prophylaxis is strongly recommended for patients with diffuse large B cell lymphoma (DLBCL) who are at high risk of developing TLS 1.

Prophylactic Measures

The following prophylactic measures are advised:

• Aggressive hydration with at least 2-3 liters of intravenous fluids per day 1
• Allopurinol 300 mg orally once daily, or rasburicase 3-6 mg intravenously as a single dose 1
• Monitoring of uric acid, potassium, phosphate, and calcium levels every 6-8 hours for the first 24-48 hours after initiation of chemotherapy 1

Administration and Dosage

• Allopurinol should be started 1-2 days before initiation of chemotherapy and continued for 7-10 days, or until the risk of TLS has decreased 1
• Rasburicase can be administered as a single dose, but may be repeated if uric acid levels remain elevated 1
• In patients with renal impairment, the dose of allopurinol should be adjusted, and rasburicase should be used with caution 1

Additional Recommendations

• Avoid using NSAIDs and diuretics, which can increase the risk of TLS 1
• Consider administering TLS prophylaxis in a hospital setting for high-risk patients, where close monitoring and supportive care can be provided 1

From the FDA Drug Label

A total of 342 adults with either leukemia, lymphoma, or other hematologic malignancy received Elitek in five 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. 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 patients with diffuse large B cell lymphoma (DLBCL) include:

• Rasburicase (Elitek) administration to reduce uric acid levels
• Monitoring of laboratory parameters for hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia
• Assessment of renal function to prevent renal failure or injury
• Use of allopurinol in combination with rasburicase or as an alternative for patients who cannot receive rasburicase 2 Key points:
• Rasburicase is effective in reducing uric acid levels and preventing clinical TLS
• Close monitoring of patients at high risk or potential risk for TLS is necessary to prevent complications
• A combination of rasburicase and allopurinol may be used to manage hyperuricemia in some patients 2

From the Research

Prophylactic Measures for Tumor Lysis Syndrome (TLS) in Patients with Diffuse Large B Cell Lymphoma (DLBCL)

• The mainstays of TLS prevention include:
  • Aggressive hydration
  • Control of hyperuricemia with allopurinol and rasburicase treatment 3
  • Close monitoring of electrolyte abnormalities 3
• Prophylaxis with allopurinol and rasburicase is recommended in all patients who are at an increased risk for tumor lysis syndrome 4
• A single-dose of rasburicase (0.1-0.2 mg/kg) can be effective in preventing progression of TLS in patients with lymphoma at high risk for TLS 5
• Fractionated rituximab, an anti-CD20 antibody, may also be a feasible approach in preventing clinical TLS, especially when used in addition to preventive strategies such as hyperhydration, urate-lowering treatments, and a steroid prophase strategy 6

Patient-Specific Considerations

• Patients with high-grade lymphomas, acute lymphoblastic leukemia, and those with a high proliferative rate and/or a large tumor burden are at increased risk for TLS 3
• Patients with end-stage renal disease (ESRD) may require aggressive treatments with daily hemodialysis and allopurinol rather than hydration to manage TLS 7
• Close monitoring of electrolyte abnormalities and renal function is crucial in patients at risk for TLS 3

Treatment Strategies

• Rasburicase can be used to prevent TLS in patients with lymphoma at high risk for TLS, with a single-dose being effective in some cases 5
• Allopurinol can be used to control hyperuricemia and prevent TLS 4, 3
• Fractionated rituximab may be used in addition to preventive strategies to prevent clinical TLS 6