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Pitfalls, prevention, and treatment of hyperuricemia during tumor lysis syndrome in the era of rasburicase (recombinant urate oxidase)

机译:rasburicase(重组尿酸氧化酶)时代的肿瘤溶解综合征期间高尿酸血症的陷阱,预防和治疗

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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.
机译:除水合和尿碱化外,别嘌呤醇已成为治疗具有高肿瘤负担,易发生肿瘤溶解综合征的患者的高尿酸血症的标准药物。然而,这种药物常常不能有效地预防和治疗这种并发症。已经证明,rasburicase(重组尿酸氧化酶)可有效降低血液系统恶性肿瘤伴高尿酸血症或高发性尿酸血症患者的尿酸水平,并防止尿酸积累。葡萄果糖酶作用于嘌呤分解代谢途径的末端,与别嘌呤醇不同,它不诱导黄嘌呤或次黄嘌呤的积累。它的快速起效和降低预先存在的尿酸水平升高的能力是rasburicase相对于别嘌呤醇的优势。 Rasburicase是别嘌呤醇的有效替代品,可迅速降低尿酸水平,改善患者的电解质状况并逆转肾功能不全。该药物最初是在患有急性淋巴细胞性白血病和侵袭性非霍奇金淋巴瘤的儿科患者中研究的,似乎在具有类似淋巴恶性肿瘤或处于高肿瘤溶解综合征风险的成年人中显示出可比的益处。当前和将来的试验将评估替代药物和不同时间表的rasburicase,以维持其功效,同时降低其成本。该综述提供了TLS的发病机理,实验室和临床表现的全面而详细的综述,以及已经在儿科和成年患者中进行的临床研究。

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