title: Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients.
abstract: BACKGROUND
  High-dose methotrexate (HDMTX)-induced acute kidney injury is a rare but life-threatening complication. The methotrexate rescue agent glucarpidase rapidly hydrolyzes methotrexate to inactive metabolites. The authors retrospectively reviewed glucarpidase use in pediatric cancer patients at their institution and evaluated whether subsequent resumption of HDMTX was tolerated.
  
  
  METHODS
  Clinical data and outcomes of all patients who received glucarpidase after HDMTX administration were reviewed.
  
  
  RESULTS
  Of 1141 patients who received 4909 courses of HDMTX, 20 patients (1.8% of patients, 0.4% of courses) received 22 doses of glucarpidase. The median glucarpidase dose was 51.6 U/kg (range, 13-65.6 U/kg). At the time of administration, the median plasma methotrexate concentration was 29.1 μM (range, 1.3-590.6 μM). Thirteen of the 20 patients received a total of 39 courses of HDMTX therapy after glucarpidase. The median time to complete methotrexate excretion was 355 hours (range, 244-763 hours) for the HDMTX course during which glucarpidase was administered, 90 hours (range, 66-268 hours) for the next HDMTX course, and 72 hours (range, 42-116 hours) for subsequent courses. The median peak serum creatinine level during these HDMTX courses was 2.2 mg/dL (range, 0.8-9.6 mg/dL), 0.8 mg/dL (range, 0.4-1.6 mg/dL), and 0.6 mg/dL (range, 0.4-0.9 mg/dL), respectively. One patient experienced nephrotoxicity upon rechallenge with HDMTX. Renal function eventually returned to baseline in all patients, and no patient died as a result of methotrexate toxicity.
  
  
  CONCLUSIONS
  The current results indicated that it is possible to safely resume HDMTX therapy after glucarpidase treatment for HDMTX-induced acute kidney injury.
authors.affiliation: Department of Pharmaceutical Services, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Christensen
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pauley
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Molinelli
authors.forename: John C
authors.initials: JC
authors.lastname: Panetta
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ward
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: James M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: Scott C
authors.initials: SC
authors.lastname: Howard
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Pappo
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Crews
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019233:Retreatment; D055815:Young Adult; D011623:gamma-Glutamyl Hydrolase / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D011623:gamma-Glutamyl Hydrolase; D008727:Methotrexate