Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant

Leuk Lymphoma. 2014 Dec;55(12):2866-73. doi: 10.3109/10428194.2014.897701. Epub 2014 May 27.


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.

Keywords: Clofarabine; acute kidney injury; glomerular filtration rate; pharmacokinetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / diagnosis
  • Adenine Nucleotides / administration & dosage
  • Adenine Nucleotides / adverse effects*
  • Adenine Nucleotides / pharmacokinetics
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Arabinonucleosides / administration & dosage
  • Arabinonucleosides / adverse effects*
  • Arabinonucleosides / pharmacokinetics
  • Area Under Curve
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clofarabine
  • Female
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Severity of Illness Index
  • Transplantation Conditioning / adverse effects*
  • Transplantation, Homologous


  • Adenine Nucleotides
  • Antimetabolites, Antineoplastic
  • Arabinonucleosides
  • Clofarabine