Introduction—optimal treatment of malignancies associated with hyperuricemia

Abstract

A SYMPOSIUM entitled “Optimal Treatment of Malignancies Associated With Hyperuricemia” was held prior to the 42nd Annual Meeting of the American Society of Hematology in December 2000 in San Francisco, CA. Sponsored by the University of Tennessee, the symposium featured a group of leading clinical oncologists who reviewed the current treatment of malignancies associated with tumor lysis syndrome (TLS), with a focus on the current management of hyperuricemia, a key metabolic disorder in TLS. This supplement to Seminars in Hematology highlights novel strategies that may be implemented to reduce the morbidity and mortality associated with TLS, especially in patients with lymphoproliferative malignancies. TLS is a potentially fatal and metabolic complication that can occur in some patients with cancer.6,9,17 It is often associated with malignancies that have large tumor burdens and high proliferative fractions, including high-grade lymphomas and leukemias with high tumor burden.6~9~10~17~i9 Hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia are the hallmark signs of TLS and occur when the kidneys cannot process and excrete the large amounts of intracellular contents (including purine, potassium, and phosphorus) released during chemotherapy-induced cell lysis. The increased serum levels of these byproducts tax the mechanisms of normal renal excretion and can progress rapidly to acute renal failure and occasional fatal metabolic derangernent.7~10~17~i8 In some patients with cancer, the malignancy itself can raise uric acid levels, and treatment with cytotoxic agents, especially at high doses, further worsens the condition of hyperuricemia. TLS usually occurs at the time of maximal tumor cell lysis, beginning a few hours after the initiation of chemotherapy and persisting for 3 to 7 days. l7 In a comprehensive article, Dr Sima Jeha has provided an overview of the etiology and management of hyperuricemia and TLS. Uric acid is the end product of purine metabolism that is normally excreted by the kidneys.ir In the liver, hypoxanthine and xanthine are catalyzed sequentially by xanthine oxidase to uric acid.lg Uric acid is poorly soluble in the highly acidic environment of the urine, and hence there is a significant potential for urate crystallization in the renal tubules as uric acid concentrations increase.17,19 In normal individuals, moderately elevated serum levels of uric acid are usually corrected by increased excretion. In patients with cancer, however, uric acid crystals can cause an obstructive uropathy, decreasing the clearance of urates, as well as phosphorus, and increasing the potential for acute renal failure. To prevent renal failure, management of TLS is aimed at increasing urine production, decreasing uric acid and phosphorus concentrations, and increasing the solubility of uric acid and phosphorus in