Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modification by covalent attachment of monomethoxypolyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of injected enzymes, making their use as therapeutic agents feasible. We report the first clinical use of PEG-modified Arthrobacter protoformiae uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma and renal insufficiency who was allergic to allopurinol. Two intramuscular injections totaling 3 U/kg body weight during the first 30 hours of treatment lowered the plasma urate level from 910 to 190 mumol/L (15.3 to 3.2 mg/dL), after which a dose of 2 U/kg every 5 to 6 days maintained the plasma urate level at 540 mumol/L (9 mg/dL) or lower. After the injection of PEG-uricase, uricase activity appeared in plasma rapidly, peaking within 24 hours and persisting for approximately 5 days; an inverse relation between plasma uricase activity and plasma urate concentration was noted. The agent was nontoxic and well tolerated. No antibody to either PEG-uricase or unmodified uricase developed over a 3-week period, during which four doses of PEG-uricase were administered. Because of its long circulating life, PEG-uricase is probably a more effective hypouricemic agent than unmodified uricase, which has previously had limited use. As an adjunct to cytolytic therapy for hematologic malignancies when protection from hyperuricemia is needed rapidly, PEG-uricase deserves further study.
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PMID:Use of polyethylene glycol-modified uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma. 328 28

Standard prophylaxis and treatment of malignancy-associated hyperuricemia in the USA has been allopurinol with vigorous hydration, urinary alkalinization and osmotic diuresis. Urate oxidase, the enzyme that converts uric acid to allantoin (a readily excreted metabolite that has 5- to 10-fold higher solubility than uric acid), is an alternative therapy; however, few published findings support this practice. Between February 1994 and December 1996, we administered non-recombinant urate oxidase (Uricozyme) to 126 children with newly diagnosed non-B cell acute lymphoblastic leukemia (ALL) during the first 5 days of chemotherapy with methotrexate, 6-mercaptopurine or both. Their blood levels of uric acid and other indicators of tumor lysis were measured at diagnosis and during treatment and then compared with findings in 129 similarly treated historical controls who had received allopurinol to control hyperuricemia. Clinical responses to urate oxidase were also determined in eight patients with newly diagnosed B cell ALL or advanced-stage non-Hodgkin lymphoma. Patients treated with urate oxidase had rapid and 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 or non-Hodgkin lymphoma. None of the patients required dialysis for acute renal failure. Six (4.5%) of the 134 children given urate oxidase had allergic reactions, manifested primarily by urticaria, bronchospasm and hypoxemia. Thus, non-recombinant urate oxidase is a more effective uricolytic agent than allopurinol but is associated with acute hypersensitivity reactions, even in patients without a history of allergy.
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PMID:Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies. 936 11

Along with hydration and urinary alkalinization, allopurinol has been the standard agent for the management of hyperuricemia in patients with a high tumor burden who are at risk for tumor lysis syndrome. However, this agent often fails to prevent and treat this complication effectively. Rasburicase, a recombinant urate oxidase, acts at the end of the purine catabolic pathway and, therefore, does not induce accumulation of xanthine or hypoxanthine, which can precipitate in the kidneys and lead to impaired renal function. Rasburicase may represent an effective alternative to allopurinol in rapidly reducing uric acid levels, improving patients' electrolyte status, and reversing renal insufficiency. The drug initially was studied in pediatric patients with acute lymphoblastic leukemia and aggressive non-Hodgkin lymphoma; data may suggest comparable benefit in adults with similar lymphoid malignancies. Current and future trials will evaluate alternate doses and schedules of rasburicase to maintain its efficacy while reducing its cost.
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PMID:Managing malignancy-associated hyperuricemia with rasburicase. 1579 44

Along with hydration and urinary alkalinization, allopurinol has been the standard agent for the management of hyperuricemia in patients with a high tumor burden at risk of tumor lysis syndrome; however, this agent often fails to prevent and treat this complication effectively. Rasburicase (recombinant urate oxidase) has been shown to be effective in reducing uric acid and preventing uric acid accumulation in patients with hematologic malignancies with hyperuricemia or at high risk of developing it. Rasburicase acts at the end of the purine catabolic pathway and, unlike allopurinol, does not induce accumulation of xanthine or hypoxanthine. Its rapid onset of action and the ability to lower pre-existing elevated uric acid levels are the advantages of rasburicase over allopurinol. Rasburicase represents an effective alternative to allopurinol to promptly reduce uric acid levels, improve patient's electrolyte status, and reverse renal insufficiency. The drug, initially studied in pediatric patients with acute lymphoblastic leukemia and aggressive non-Hodgkin lymphoma, seems to show comparable benefit in adults with similar lymphoid malignancies or at high risk of tumor lysis syndrome. Current and future trials will evaluate alternative doses and different schedules of rasburicase to maintain its efficacy while reducing its cost. The review provides a comprehensive and detailed review of pathogenesis, laboratory, and clinical presentation of TLS together with clinical studies already performed both in pediatric and adult patients.
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PMID:Pitfalls, prevention, and treatment of hyperuricemia during tumor lysis syndrome in the era of rasburicase (recombinant urate oxidase). 1970 36