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

J Hematol Oncol. 2011 Oct 13;4:42. doi: 10.1186/1756-8722-4-42.

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).

Conclusion: 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.

Trial registration: ISRCTN: ISRCTN16757172.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Intelligence / drug effects*
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*

Substances

  • Antineoplastic Agents
  • Methotrexate

Associated data

  • ISRCTN/ISRCTN16757172