From the Guidelines
Allopurinol should not be used as the first-line treatment for preventing tumor lysis syndrome (TLS) in patients with acute lymphoid leukemia (ALL) due to its limitations and potential side effects, as evidenced by the most recent study from 2024 1. Instead, rasburicase is recommended as the preferred agent for managing hyperuricemia in patients at high risk of TLS, as it provides a rapid and complete degradation of uric acid to allantoin, allowing for prompt continuation of chemotherapy. The use of allopurinol is associated with several limitations, including its inability to reduce pre-existing uric acid levels, potential to cause xanthine crystal precipitation in the renal tubules, and requirement for dose reductions of other purine-based chemotherapeutic agents. Additionally, allopurinol has been associated with hypersensitivity reactions, which may manifest as cutaneous rash or fever, as reported in 10 cases in a study by Coiffier et al 1. In contrast, rasburicase has been shown to be effective in reducing uric acid levels and preventing TLS in both pediatric and adult patients, with a favorable safety profile, as demonstrated in studies by Bosly et al, Pession and Barbieri, and Shin et al 1. Therefore, rasburicase is the preferred agent for preventing TLS in patients with ALL, and allopurinol should only be considered as an alternative in patients who are unable to receive rasburicase. It is essential to monitor patients for potential side effects and adjust treatment accordingly, prioritizing morbidity, mortality, and quality of life as the primary outcomes. Adequate hydration and monitoring of uric acid levels are crucial in preventing and managing TLS, and patients should be closely observed for signs of laboratory TLS, which implies the presence of at least two biochemical alterations among hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. The management of ALL includes complex, intensive multi-agent chemotherapy regimens, and the treatment approach represents one of the most complex and intensive programs in cancer therapy, as outlined in the NCCN Guidelines for ALL 1. Overall, the use of rasburicase as the first-line treatment for preventing TLS in patients with ALL is supported by the most recent and highest-quality evidence, and its use should be prioritized over allopurinol to minimize the risk of TLS and improve patient outcomes.
From the FDA Drug Label
Allopurinol tablets are indicated in: ... 2. the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels Allopurinol can be used in the management of patients with leukemia, including acute lymphoid leukemia, who are receiving cancer therapy that causes elevations of serum and urinary uric acid levels. The primary purpose of allopurinol in this context is to reduce serum and urinary uric acid concentrations, which can become elevated as a result of cancer treatment.
- Key points:
- Allopurinol is used to manage uric acid levels in leukemia patients undergoing cancer therapy.
- Its use is intended to prevent complications associated with elevated uric acid levels. 2
From the Research
Allopurinol Use for Acute Lymphoid Leukemia
- Allopurinol has been used to manage hyperuricemia in patients with acute lymphoid leukemia, particularly those at risk of tumor lysis syndrome 3, 4, 5, 6.
- However, allopurinol may not be effective in preventing and treating tumor lysis syndrome in all cases, and alternative treatments such as rasburicase may be more effective 3, 5.
- The use of allopurinol in combination with hydration and urinary alkalinization has been shown to reduce the risk of tumor lysis syndrome in patients with acute lymphoid leukemia 4, 6.
- Risk factors for tumor lysis syndrome in patients with acute lymphoid leukemia include high white blood cell counts, elevated lactate dehydrogenase levels, and high uric acid levels 7.
Tumor Lysis Syndrome Prevention and Treatment
- Prevention and treatment measures for tumor lysis syndrome include intravenous hydration, use of allopurinol and rasburicase, management of electrolyte abnormalities, and renal replacement therapy 3, 4, 5, 6.
- The use of urine alkalinization remains controversial, and its effectiveness in preventing tumor lysis syndrome is not well established 6.
- A predictive model for estimating individual risk of tumor lysis syndrome has been developed, based on pretreatment white blood cell counts, uric acid levels, and lactate dehydrogenase levels 7.
Alternative Treatments
- Rasburicase, a recombinant form of the enzyme urate oxidase, has been shown to be effective in reducing uric acid levels and preventing tumor lysis syndrome in patients with acute lymphoid leukemia 3, 5.
- Rasburicase may be a more effective alternative to allopurinol in preventing and treating tumor lysis syndrome, particularly in patients at high risk of this complication 3, 5.