title: Rational use of rasburicase for the treatment and management of tumor lysis syndrome.
abstract: Purpose There is a lack of high-level evidence identifying meaningful outcomes and the optimal place in therapy of rasburicase in patients with, or at high risk for tumor lysis syndrome. The primary objective of this study was to evaluate and characterize outcomes resulting from an institution-specific guideline emphasizing supportive care, xanthine oxidase inhibitors, and lower doses of rasburicase. Methods In this retrospective chart review, we compared conservative rasburicase dosing, in accordance with newly developed UMHS tumor lysis syndrome guidelines, with aggressive rasburicase in adult patients (≥ 18 years of age) with hematological or solid tumor malignancies, and a uric acid level between 8 and 15 mg/dL. The primary efficacy outcome assessed the difference in the proportion of patients achieving a uric acid level <8 mg/dL within 48 h using a one-sided noninferiority test. The principle safety outcomes analyzed included incidence of acute kidney injury and hemodialysis requirement. Results One hundred sixty-one patients met inclusion criteria and were included in the study. Within 48 h of an elevated uric acid level, treatment was successful in 97.03% of patients in the conservative group, as compared with 98.33% in the aggressive group (difference, 1.3 percentage points; 95% confidence interval [CI], -3.33 to 5.93). Furthermore, there was no difference in the proportion of patients requiring hemodialysis (2.97% vs. 10.0%, p-value 0.079), or incidence of acute kidney injury (4.0% vs. 12.5%, p-value 1.00) between the treatment group and control group, respectively. Conclusions Conservative rasburicase use was noninferior to aggressive rasburicase use in patients with or at high risk for tumor lysis syndrome.
authors.affiliation: Department of Pharmacy Services and Clinical Sciences, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Suhail A
authors.initials: SA
authors.lastname: Shaikh
authors.affiliation: Department of Pharmacy Services and Clinical Sciences, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Marini
authors.affiliation: Department of Pharmacy Services and Clinical Sciences, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Hough
authors.affiliation: Department of Pharmacy Services and Clinical Sciences, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Perissinotti
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000175:diagnosis; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D019468:Disease Management; D005260:Female; D006074:Gout Suppressants / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000639:trends; D012189:Retrospective Studies; D016896:Treatment Outcome; D015275:Tumor Lysis Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D014503:Urate Oxidase / Q000008:administration & dosage* / Q000009:adverse effects; D014527:Uric Acid / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D006074:Gout Suppressants; C469709:rasburicase; D014527:Uric Acid; D014503:Urate Oxidase
keywords: Rasburicase; hyperuricemia; leukemia; lymphoma; tumor lysis syndrome