title: Risk factors for high-dose cytarabine neurotoxicity: an analysis of a cancer and leukemia group B trial in patients with acute myeloid leukemia.
abstract: OBJECTIVE
  We analyzed pretreatment characteristics of patients with postremission acute myeloid leukemia (AML) treated with high-dose cytarabine (HIDAC) during a recent Cancer and Leukemia Group B (CALGB) trial to determine risk factors associated with HIDAC neurotoxicity.
  
  
  METHODS
  One hundred seventy-six patients received at least one course of HIDAC as part of a CALGB protocol designed to determine the optimal dose of cytarabine (ara-C) for postremission treatment of AML. HIDAC consisted of 3 g/m2 ara-C infused over 3 hours at 12-hour intervals on days 1, 3, and 5. The pretreatment characteristics of 170 patients were available for risk analyses.
  
  
  RESULTS
  Eighteen patients (10%) experienced neurotoxicity. Univariate analyses demonstrated associations between the occurrence of neurotoxicity and elevated serum creatinine, age, and alkaline phosphatase (AP). Multivariate analysis showed that these variables were independent risk factors. These findings were used to construct a risk model with the following parameters: creatinine greater than or equal to 1.2 mg/dL, age greater than or equal to 40 years, and AP greater than or equal to 3 x normal. Seventeen of 46 (37%) patients with two or more of these criteria developed neurotoxicity compared with one of 124 (1%) patients with one or none. The sensitivity and specificity of this model were 94% and 81%, respectively.
  
  
  CONCLUSIONS
  We conclude that patients with two or more of the following parameters may be at increased risk for HIDAC neurotoxicity: (creatinine greater than or equal to 1.2 mg/dL, age greater than or equal to 40, and AP greater than or equal to 3 x normal). However, this model should be confirmed by analysis of additional groups of patients treated with HIDAC.
authors.affiliation: Division of Biostatistics and Epidemiology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
authors.forename: E H
authors.initials: EH
authors.lastname: Rubin
authors.forename: J W
authors.initials: JW
authors.lastname: Andersen
authors.forename: D T
authors.initials: DT
authors.lastname: Berg
authors.forename: C A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: R J
authors.initials: RJ
authors.lastname: Mayer
authors.forename: R M
authors.initials: RM
authors.lastname: Stone
mesh_terms: D000208:Acute Disease; D000328:Adult; D000367:Age Factors; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000097:blood / Q000139:chemically induced*; D012307:Risk Factors
chemical_list: D003561:Cytarabine; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase