Hyperuricemia with tumor lysis syndrome

Prophylaxis and treatment of hyperuricemia associated with tumor lysis syndrome. ALL, acute lymphoblastic leukemia AML, acute myelogenous leukemia IV, intravenous. (Data from refs. 32 and 33.)... 

Tumor lysis syndrome together with increased cytokine release can occur with drugs such as clofarabine therefore, besides intensified hydration, allopurinol should be given if hyperuricemia is expected (321). 

There are several types of adverse effects that the cytostatic drugs have in common. These include hyperuricemia (as a result of tumor lysis syndrome), bone marrow suppression, oral mucositis, gastrointestinal discomfort, and alopecia. These are dealt with under the relevant headings below. 

AUopurinol inhibits xanthine oxidase and prevents the synthesis of urate from hypoxanthine and xanthine. It is used to treat hyperuricemia in patients with gout and to prevent it in those with hematological malignancies about to undergo chemotherapy (acute tumor lysis syndrome). Even though underexcretion rather than overproduction is the underlying defect in most gout patients, allopurinol remains effective therapy. 

Allopurinol is contraindicated in patients who have exhibited serious adverse fffects or hypersensitivity reactions to the medication, and in nursing mothers and children, except those with malignancy or certain inborn errors of purine metabolism (e.g., Lesch-Nyhan syndrome). Allopurinol generally is used in complicated hyperuricemia (see above), to prevent acute tumor lysis syndrome, or in patients with hyperuricemia post-transplantation. If necessary, it can be used in conjunction with uricosuric agents. 

Several enzyme therapies are also used in the treatment of cancer. For instance, rasburicase (uricase Elitek EC 1.7.3.3) is used in the treatment of hyperuricemia due to tumor lysis syndrome (TLS). This is a potentially life-threatening condition that is associated with rapidly developing tumors, such as those found in lymphoma and leukemia, in patients undergoing chemotherapy. The incidence of hyperuricemia in these patients is close to 20% [88]. Uricase is an interesting enzyme, because it is found in most mammals, with the exception of humans, where the gene contains a nonsense mutation [89]. Rasburicase is well tolerated, has a very fast onset of action, and is administered intravenously once a day. However, the enzyme cannot be used on patients with glucose-6-phosphate dehydrogenase deficiency [90]. The... 

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