Lillywhite, Leasha Michelle;
(2004)
The long-term outcome of childhood leukaemia: Neuropsychological and neuroimaging investigations.
Doctoral thesis (Ph.D.), University College London (United Kingdom).
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Abstract
The recent introduction of pre-symptomatic central nervous system (PCNS) therapy in the treatment of childhood acute lymphoblastic leukaemia (ALL) has significantly improved the chances of long-term (LT) survival. However, the LT survival of ALL can be complicated by cognitive and behavioural impairments, and these problems may be related to the administration of PCNS therapy. This thesis investigated the role of PCNS therapies in determining the LT outcome of childhood ALL. In particular, attempts were made to identify the functional impairments associated with two PCNS therapies currently used in the treatment of standard-risk ALL, and to relate the profile of deficits identified to underlying structural abnormalities. Investigations were conducted in accordance with a proposed model of pathology. This model was based on the biochemical actions of the main component of both PCNS therapies, methotrexate (MTX). 32 LT survivors and 14 siblings participated in this research. Survivors were randomised to receive either (1) HD MTX + IT MTX + FAR (HD group), or (2) IT MTX-only (IT group) as PCNS therapy. Participants completed a battery of neuropsychological tests assessing the functional integrity of the frontal lobes and corpus callosum. In addition, the structural integrity of the brain was evaluated using conventional neuroradiological assessment and voxel-based morphometry (VBM). The neuropsychological and conventional neuroradiological investigations revealed minimal differences between the survivor and sibling groups. The VBM analyses, however, revealed common, subtle differences in brain structure between the survivors and their siblings. The differences included subtle pathology of the thalamus, caudate nucleus, and corona radiata. The pathology was regionally specific apparently sparing, for example, the pons and cerebellum. The methods used in the current research, however, were unable to establish a clear relationship between the subtle pathology identified and impairments in cognitive function.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | The long-term outcome of childhood leukaemia: Neuropsychological and neuroimaging investigations |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | (UMI)AAIU643795; Biological sciences; Leukemia |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10103426 |
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