URATE OXIDASE IN PREVENTION AND TREATMENT OF HYPERURICEMIA ASSOCIATEDWITH LYMPHOID MALIGNANCIES

Standard prophylaxis and treatment of malignancy-associated hyperurice mia in the USA has been allopurinol with vigorous hydration, urinary a lkalinization and osmotic diuresis. Urate oxidase, the enzyme that con verts uric acid to allantoin (a readily excreted metabolite that has 5 - to 10-fold higher solubility than uric acid), is an alternative ther apy; however, few published findings support this practice. Between Fe bruary 1994 and December 1996, we administered non-recombinant urate o xidase (Uricozyme) to 126 children with newly diagnosed non-B cell acu te lymphoblastic leukemia (ALL) during the first 5 days of chemotherap y with methotrexate, B-mercaptopurine or both. Their blood levels of u ric acid and other indicators of tumor lysis were measured at diagnosi s and during treatment and then compared with findings in 129 similarl y treated historical controls who had received allopurinol to control hyperuricemia, Clinical responses to urate oxidase were also determine d in eight patients with newly diagnosed B cell ALL or advanced-stage non-Hodgkin lymphoma. Patients treated with urate oxidase had rapid an d significantly greater decreases in their blood uric acid levels than did the historical controls (median maximal level during treatment, 2 .3 vs 3.9 mg/dl, P < 0.001). They also had lower creatinine (0.6 vs 0. 7 mg/dl, P = 0.01) and blood urea nitrogen (11 vs 24 mg/dl, P < 0.001) levels. Similar findings were made in the eight cases of B cell ALL o r non-Hodgkin lymphoma. None of the patients required dialysis for acu te renal failure. Six (4.5%) of the 134 children given urate oxidase h ad allergic reactions, manifested primarily by urticaria, bronchospasm and hypoxemia. Thus, non-recombinant urate oxidase is a more effectiv e uricolytic agent than allopurinol but is associated with acute hyper sensitivity reactions, even in patients without a history of allergy.