Neuropsychological Effects of Cranial Irradiation in Young Children With Acute Lymphoblastic Leukemia 9 Months After Diagnosis

MacLean, William E.; Noll, Robert B.; Stehbens, James A.; Kaleita, Thomas A.; Schwartz, Edward; Whitt, J. Kenneth; Cantor, Nancy; Waskerwitz, Mary J.; Ruymann, F. B.; Novak, Louis J.; Woodard, Austin; Hammond, G. Denman

doi:10.1001/archneur.1995.00540260060017

Cited by 37 publications

(14 citation statements)

References 25 publications

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“…Several possibilities may explain these discrepant results. Firstly, the majority of studies showing adverse effects of cranial radiotherapy included very young children, and in many the adverse effects of radiotherapy were strongly associated with the younger age groups [10,14,18,24,25,29,30]. Since radiotherapy is thought to cause neurotoxicity predominantly by demyelination [31] and myelination is not complete until much later in childhood, younger children would be expected to be particularly vulnerable.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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BackgroundThe 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).ResultsThere 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).ConclusionChildren 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 registrationISRCTN: ISRCTN16757172

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Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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“…Specifically, there is some suggestion that the hippocampus may be implicated (Dupont et al, 2000). In contrast to findings from the CRT literature, even when neuropathology has been identified, the functional impact of these findings has been unclear (Anderson et al, 1994;MacLean et al, 1995;Mulhern, Ochs, & Fairclough, 1992). The absence of findings may not necessarily reflect lack of deficit, but may suggest that previous investigations have used measures not sensitive to the deficits demonstrated following this treatment.…”

Section: Impairments Of Attention Following Treatment With Cranial Irmentioning

confidence: 93%

Impairments of Attention Following Treatment With Cranial Irradiation and Chemotherapy in Children

Anderson

Godber

Smibert

et al. 2004

Journal of Clinical and Experimental Neuropsychology

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Neurobehavioral impairments are frequently reported following treatment for childhood cancers, with cranial irradiation (CRT). This study investigated attention and information processing skills, predicting that these skills would be impaired due to the vulnerability of cerebral white matter in early childhood. Three treatment groups were studied: (i) CRT+chemotherapy (n = 35); (ii) chemotherapy alone (n = 19); (iii) healthy children (n = 35). All children were aged 9 to 16 years at time of assessment, with no pre-diagnosis history of neurologic, developmental, or psychiatric disorder. Children were administered a series of task measuring processing speed and sustained, selective, and shifting attention. For children treated with CRT + chemo, results identified residual deficits in processing speed for complex tasks, selective and shifting attention. In contrast, processing speed was intact for simple tasks, and there was no clear evidence of deterioration in performance over time, as might be expected in the presence of a sustained attention deficit. Children treated with chemotherapy alone demonstrated generally intact attentional skills. However, this group did record an increasing number of attentional lapses over time on tasks tapping sustained attention skills.

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“…Because children with ALL are treated according to risk-stratified protocols, random assignment is only ethical within risk-stratified cohorts [see MacLean et al, 1995;Waber et al, 2004Waber et al, , 2007. Investigation of the role of demographic variables (e.g., age, sex) on neurocognitive outcomes is complicated by the fact that these same variables are often used in the initial risk stratification and, inevitably, are confounded with treatment.…”

Section: Methodological Issuesmentioning

confidence: 99%

“…On-treatment studies IQ scores of children on active CO treatment are at least average [Williams et al, 1986;MacLean et al, 1995;Krappman et al, 2007;Moore et al, 2008], with no evidence of decline over the course of treatment [Copeland et al, 1988;Dowell et al, 1989;Brown et al, 1996;Copeland et al, 1996;Carey et al, 2007]. However, difficulties with perceptual motor speed [Copeland et al, 1988[Copeland et al, , 1996, working memory [Carey et al, 2007], academic achievement [Brown et al, 1996], and fine motor skills [Dowell et al, 1989;Hockenberry et al, 2007] have been reported.…”

Section: Chemotherapy-onlymentioning

confidence: 99%

Neurodevelopmental sequelae of pediatric acute lymphoblastic leukemia and its treatment

Janzen

Spiegler

2008

Dev Disabil Res Revs

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This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research. It is concluded that neurocognitive outcomes for the majority of children with standard-risk ALL treated according to current chemotherapy protocols is relatively good, but subgroups of children are more significantly compromised. As medical treatments advance and survival rates continue to improve, neurocognitive outcomes and other quality of life indicators will become increasingly important. Preventing or ameliorating treatment-related neuropsychological sequelae represents the next major challenge in pediatric ALL.

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Neuropsychological Effects of Cranial Irradiation in Young Children With Acute Lymphoblastic Leukemia 9 Months After Diagnosis

Cited by 37 publications

References 25 publications

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

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

Impairments of Attention Following Treatment With Cranial Irradiation and Chemotherapy in Children

Neurodevelopmental sequelae of pediatric acute lymphoblastic leukemia and its treatment

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