Managing tumor lysis syndrome in 2010.

In this issue of Leukemia and Lymphoma, Darmon et al. report that patients with renal injury manifest by an acute rise in serum creatinine or the development of oliguria without a rise in the serum creatinine (presumably insufficient time has elapsed for creatinine to accumulate in the serum) have a significantly shorter survival than patients who develop tumor lysis syndrome but maintain adequate renal function. All patients with acute renal injury in this study had a serum creatinine, at ICU admission, of greater than 126 mmol/L of creatinine (serum creatinine41.4 mg/dL). At 6 months, patients with acute renal injury had a survival of 35% compared with 85% in the no acute renal injury group. This cohort is not representative of all patients with tumor lysis syndrome because milder forms were cared for outside of the intensive care unit and were excluded from this study [1]. Tumor lysis syndrome is characterized by the acute development of hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and renal injury after chemotherapy [2]. The development of tumor lysis syndrome has three prerequisites. The tumor mass needs to be high; the tumor itself needs to be highly sensitive to systemic chemotherapy, and a high fraction of cells must be destroyed by systemic chemotherapy. Tumor lysis syndrome was first described in the management of Burkitt lymphoma, a consequence of the high sensitivity of this malignancy to treatment with cyclophosphamide [3]. The prevalence of tumor lysis syndrome has been rising as more effective systemic chemotherapies have been developed. The majority of patients have a hematologic malignancy because the majority of patients with solid tumors have an insufficient fraction of highly chemotherapy-sensitive cells. The tumors, most commonly associated with tumor lysis syndrome today, are acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and a fraction of high-grade lymphomas. Clinical parameters predicting a high risk of tumor lysis syndrome include: elevation of the lactate dehydrogenase and a white blood cell count over 50 000/mL. The dangers associated with tumor lysis syndrome include the metabolic disturbances associated with acute hypocalcemia and hyperphosphatemia that can lead to frank tetany [4], as well as cardiac arrhythmias precipitated by the combination of hypocalcemia and hyperkalemia. The most devastating complication is the development of oliguric renal failure related to uric acid nephropathy. Historically preventative therapy necessitated alkalinization of the urine and the administration of allopurinol, an inhibitor of xanthine oxidase, preventing the conversion of hypoxanthine and xanthine, normal purine metabolites, from being converted into uric acid. As xanthine and hypoxanthine are far more soluble than uric acid, their precipitation in the renal tubule is less likely, although xanthine urolithiasis can occur [5]. Although allopurinol sharply reduced the risk of post chemotherapy hyperuricemia, the inhibition of xanthine oxidase does nothing to reduce the level of uric acid at presentation. The introduction of rasburicase has altered the natural history of this syndrome. Rasburicase is a recombinant urate oxidase and catalytically degrades uric acid. Rasburicase oxidizes uric acid, converting it to allantoin, which is 10-fold more soluble than uric acid and does not precipitate as crystals. Rasburicase is produced after the proteolytic hydrolysis of Aspergillus flavus urate oxidase, which permits the formation of oligodeoxynucleotide probes that are used to obtain DNA