title: Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia.
abstract: BACKGROUND
  Treatment of acute lymphoblastic leukemia (ALL) has included the use of prophylactic cranial irradiation in up to 20% of children with high-risk disease despite known cognitive risks of this treatment modality.
  
  
  METHODS
  Patients enrolled on the St Jude ALL Total Therapy Study XV, which omitted prophylactic cranial irradiation in all patients, were assessed 120 weeks after completion of consolidation therapy (n = 243) using a comprehensive cognitive battery. χ(2) analysis was used to compare the percentage of below-average performers among the entire ALL patient group to the expected rate based on the normative sample. Univariate logistic regression was used to estimate the effect of intensity of chemotherapy (treatment arm), age at diagnosis, and sex on the probability of below-average performance. All statistical tests were two-sided.
  
  
  RESULTS
  Overall, the ALL group had a statistically significantly higher risk for below-average performance on a measure of sustained attention (67.31% more than 1 SD below the normative mean for omission errors, P < .001) but not on measures of intellectual functioning, academic skills, or memory. Patients given higher intensity chemotherapy were at greater risk for below-average performance compared with those given lower intensity therapy on measures of processing speed (27.14% vs 6.25%, P = .009) and academic abilities (Math Reasoning: 18.60% vs 3.90%, P = .008; Word Reading: 20.00% vs 2.60%, P = .007; Spelling: 27.91% vs 3.90%, P = .001) and had higher parent-reported hyperactivity (23.00% vs 9.84%, P = .018) and learning problems (35.00% vs 16.39%, P = .005). Neither age at diagnosis nor sex was associated with risk for below-average cognitive performance.
  
  
  CONCLUSIONS
  Omitting cranial irradiation may help preserve global cognitive abilities, but treatment with chemotherapy alone is not without risks. Caregiver education and development of interventions should address both early attention deficits and cognitive late effects.
authors.affiliation: Department of Psychology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-2794, USA. heather.conklin@stjude.org
authors.forename: H M
authors.initials: HM
authors.lastname: Conklin
authors.forename: K R
authors.initials: KR
authors.lastname: Krull
authors.forename: W E
authors.initials: WE
authors.lastname: Reddick
authors.forename: D
authors.initials: D
authors.lastname: Pei
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: C H
authors.initials: CH
authors.lastname: Pui
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001288:Attention / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D016371:Cranial Irradiation / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D007278:Injections, Spinal; D007360:Intelligence / Q000187:drug effects*; D007361:Intelligence Tests; D016015:Logistic Models; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D015999:Multivariate Analysis; D018579:Patient Selection; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000523:psychology*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D015122:Mercaptopurine; D011241:Prednisone; D006854:Hydrocortisone; D008727:Methotrexate