Emerging role of rasburicase in the management of increased plasma uric acid levels in patients with hematologic malignancies.

Tumor lysis syndrome (TLS) is defined as a group of metabolic derangements that result from the massive and abrupt release of cellular components into the bloodstream after rapid lysis of tumor cells. Breakdown of released materials leads to a number of electrolyte abnormalities, including elevated uric acid concentrations in the blood (hyperuricemia), which carries potentially serious consequences. The diagnosis, prevention, and management of TLS is complicated by variability in definitions, differences in risk factors based on patient- and tumor-specific characteristics, and practitioner preferences in terms of pharmaceutical management strategies. The best prevention and management option for a particular patient depends on the patient's baseline risk for TLS development, the severity of symptoms in the event of TLS development, practical management considerations, and financial implications of treatment.

Rasburicase for the prevention and treatment of hyperuricemia in tumor lysis syndrome.

PURPOSE: To review current knowledge about tumor lysis syndrome (TLS), a set of metabolic imbalances, including hyperuricemia, that often occur during chemotherapeutic or biotherapeutic treatment of patients with hematologic malignancies. DATA SOURCE: English language journal articles indexed in PubMed. STUDY SELECTION: Recent reviews and original research articles related to TLS, hyperuricemia, and treatment of hyperuricemia were selected for inclusion. RESULTS: The incidence of TLS depends highly on the type of malignancy, its growth characteristics, and the total tumor burden. Patients are at heightened risk if they have hyperuricemia, hypovolemia, or poor renal function before anticancer therapy begins. Recently published guidelines make risk assessment and patient staging more systematic. Prophylactic measures should be used to reduce the risk for TLS in vulnerable patients. Such measures include hydration to facilitate urinary excretion and administration of allopurinol to prevent de novo production of uric acid. If hyperuricemia occurs despite preventative efforts, uric acid concentrations can be reduced with rasburicase, a recombinant, intravenously administered urate oxidase. The cost of rasburicase therapy is substantial but is considerably less than that of hemodialysis and extended hospitalization. Shorter courses or smaller doses of rasburicase than those recommended may be effective in reducing hyperuricemia in some patients, but it is important to recognize that the alternative dosing still awaits validation. CONCLUSIONS: Allopurinol and rasburicase are recommended for preventing hyperuricemia in patients at intermediate or high risk for TLS, respectively. If hyperuricemia develops despite preventative measures, rasburicase treatment is an effective method for lowering uric acid concentrations within normal limits.

A prospective, randomized, double-blind controlled trial of acetaminophen and diphenhydramine pretransfusion medication versus placebo for the prevention of transfusion reactions.

BACKGROUND: Acetaminophen and diphenhydramine are commonly used as pretransfusion medications to prevent transfusion reactions. The purpose of this study was to prospectively compare the risk of transfusion reactions in hematology/oncology patients who receive acetaminophen with diphenhydramine or placebo before transfusion. STUDY DESIGN AND METHODS: A randomized, double-blind, placebo-controlled transfusion reaction study of 315 eligible patients was performed. Inclusion criteria were patients aged 18 to 65 years admitted to the leukemia or bone marrow transplant (BMT) services. Patients were excluded if they had a known allergy to either acetaminophen or diphenhydramine or had a documented history of a febrile or allergic transfusion reaction. All blood products were administered using a leukofilter. Study medications were given 30 minutes before transfusions and no other acetaminophen or diphenhydramine was given within 4 hours of administration of the study medications. Patients were monitored for the development of reaction symptoms within 4 hours after the transfusion. RESULTS: A total of 154 active drug patients were compared to 161 placebo patients. There was no significant difference in the overall risk of transfusion reactions between the two groups. However, analysis of specific reaction types revealed a significant decrease in the risk of febrile reactions when pretransfusion medication is used in addition to bedside leukoreduction. CONCLUSIONS: Pretransfusion medication of leukemia or BMT patients without a history of transfusion reaction does not decrease the overall risk of transfusion reactions. However, pretransfusion medication may decrease the risk of febrile nonhemolytic transfusion reactions to leukoreduced blood products.