Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant
Year: 2014
Type: article
Abstract: We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal.
Institutions: University of Chicago, Weill Cornell Medicine
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Busulfan conditioning: optimization, kinetics, genomics, Immunologic and pharmacologic studies in allotransplant, Mechanisms of anemia of chronic inflammation and aging in mice., Developing an Oncology Workforce for the 21st Century, PACTTE-Partnership for Anemia: Clinical and Translational Trials in the Elderly, Medical Scientist Training Program, Cancer Center Support Grant
OpenAlex ID: W2132307884