title: The relationship of sex and treatment modality to neuropsychologic outcome in childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Long-term adverse neurobehavioral sequelae frequently are observed in pediatric patients treated for acute lymphoblastic leukemia (ALL). To clarify the relative contribution of cranial irradiation (CRT) therapy and drug therapy to these outcomes, we evaluated neuropsychologic outcomes associated with different doses of CRT and intravenous (IV) methotrexate (MTX) in long-term survivors.
  
  
  METHODS
  Fifty-one patients treated for ALL on Dana-Farber Cancer Institute protocol 81-01 were evaluated by standardized cognitive and academic achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received 1,800 cGy or 2,800 cGy CRT, respectively. A subgroup of these patients was randomized to receive MTX during remission induction, either as a single low dose (LD; 40 mg/m2) or a single high dose (HD; 4 g/m2) with leucovorin rescue.
  
  
  RESULTS
  Sex and MTX randomization jointly predicted the intelligence quotient (IQ). Fifty percent of girls versus 14% of boys exhibited low IQ (less than 90; P = .01); 80% of girls who received HD MTX versus 25% of girls who received LD MTX exhibited low IQ (P = .03). In contrast, risk group better predicted performance on tasks sensitive to verbal memory and/or coding.
  
  
  CONCLUSIONS
  We conclude that (1) significant neurotoxicity occurred principally in girls; (2) increased dose intensity of IV MTX was associated with lower IQ, but only in girls; and (3) increased dose of CRT may have been associated with impairment of verbal memory and coding.
authors.affiliation: Department of Radiation Oncology, Children's Hospital, Boston, MA 02115.
authors.forename: D P
authors.initials: DP
authors.lastname: Waber
authors.forename: N J
authors.initials: NJ
authors.lastname: Tarbell
authors.forename: C M
authors.initials: CM
authors.lastname: Kahn
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: S E
authors.initials: SE
authors.lastname: Sallan
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects* / Q000528:radiation effects*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007360:Intelligence / Q000187:drug effects / Q000528:radiation effects; D007361:Intelligence Tests; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D012737:Sex Factors
chemical_list: D008727:Methotrexate