Research

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

Christina Halsey^1,2, Georgina Buck³, Sue Richards³, Faraneh Vargha-Khadem⁴, Frank Hill⁵ and Brenda Gibson^1*

• * Corresponding author: Brenda Gibson Brenda.gibson@ggc.scot.nhs.uk

Author Affiliations

¹ Department of Haematology, The Royal Hospital for Sick Children, Dalnair Street, Glasgow G3 8SJ, UK

² Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120, University Place, Glasgow G12 8TA, UK

³ Clinical Trial Service Unit, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LF, UK

⁴ Developmental Cognitive Neuroscience Unit, UCL Institute of Child Health, 30 Guildford Street, London, WC1N 1EH, UK

⁵ Department of Haematology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Journal of Hematology & Oncology 2011, 4:42 doi:10.1186/1756-8722-4-42

Published: 13 October 2011

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 × 10⁹/l) randomised to intrathecal methotrexate (n = 197) versus intrathecal and high-dose intravenous methotrexate (HDM) (n = 202), and (3) high-risk children (WCC ≥ 50 × 10⁹/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