title: The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI.
abstract: BACKGROUND
  The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS) directed therapies in childhood acute lymphoblastic leukaemia (ALL). To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1) all patients (n = 555) versus related controls (n = 311), (2) low-risk children (presenting white cell count (WCC) < 50 × 10(9)/l) randomised to intrathecal methotrexate (n = 197) versus intrathecal and high-dose intravenous methotrexate (HDM) (n = 202), and (3) high-risk children (WCC ≥ 50 × 10(9)/l, age ≥ 2 years) randomised to HDM (n = 79) versus cranial irradiation (n = 77).
  
  
  RESULTS
  There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P < 0.002) with a higher proportion of children with IQs < 80 in the patient groups (13% vs. 5% at 3 years p = 0.003).
  
  
  CONCLUSIONS
  Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes.
  
  
  BACKGROUND
  ISRCTN: ISRCTN16757172.
authors: Department of Haematology, The Royal Hospital for Sick Children, Glasgow, UK.
authors: Christina
authors: C
authors: Halsey
authors: Georgina
authors: G
authors: Buck
authors: Sue
authors: S
authors: Richards
authors: Faraneh
authors: F
authors: Vargha-Khadem
authors: Frank
authors: F
authors: Hill
authors: Brenda
authors: B
authors: Gibson
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000187:drug effects*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D008727:Methotrexate