Grant Number:	5R01CA078957-03 Interpret this number
Primary Investigator:	Mulhern, Raymond
Organization:	St. Jude Children'S Research Hospital
Project Title:	Learning Impairments Among Survivors of Childhood Cancer
Fiscal Year:	2001

DESCRIPTION (adapted from investigator's abstract): Children surviving some types of cancer, particularly acute lymphoblastic leukemia (ALL) and brain tumors, have an increased incidence of learning impairments compared to their healthy peers in the general population. These impairments, for which there is no known effective treatment, are of sufficient severity to inhibit normal academic achievement, vocational attainment, and quality of life. Previous investigations have suggested a model in which treatment-induced lesions of the brain, especially in the white matter, are an underlying cause of learning difficulties that are frequently manifested as deficits in the ability to sustain attention. The goal of this research proposal is to test the validity of this model by defining the neuroanatomic substrates of problems with attention and learning and by assessing the behavioral response of these problems to pharmacological intervention. To accomplish this goal, quantitative magnetic resonance imaging (qMRI) of the brain and neuropsychological testing will be conducted on 625 participating children treated for ALL or malignant brain tumors at 3 pediatric cancer centers. It is hypothesized that volumes of normal white matter in patients will be: a) significantly reduced compared to healthy peers, b) directly associated with the intensity of their central nervous system treatment, and c) positively correlated with their performance on measures of sustained attention and learning. A second study hypothesis is that methylphenidate will be effective in reducing their problems with attention and learning. This hypothesis will be tested with 200 children selected from the larger screened sample on the basis of objective problems with sustained attention and learning with regard to: (a) immediate (1-1/2 hr) behavioral benefits in our laboratory and (b) short-term (3 week) benefits at home and school in randomized, placebo-controlled, crossover designs, and then (c) long-term (12 month) maintenance benefits at home and school. The results of these studies will have a potentially important impact on childhood cancer by reducing the cognitive morbidities of cancer and cancer treatment and by furthering our knowledge of their biological basis.




The Impact Of Attention On Social Functioning In Survivors Of Pediatric Acute Lymphoblastic Leukemia And Brain Tumors
Authors: Moyer K.H. , Willard V.W. , Gross A.M. , Netson K.L. , Ashford J.M. , Kahalley L.S. , Wu S. , Xiong X. , Conklin H.M. .
Source: Pediatric Blood & Cancer, 2012-12-15 00:00:00.0; 59(7), p. 1290-5.
PMID: 22848032
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Parent And Teacher Ratings Of Attention During A Year-long Methylphenidate Trial In Children Treated For Cancer
Authors: Netson K.L. , Conklin H.M. , Ashford J.M. , Kahalley L.S. , Wu S. , Xiong X. .
Source: Journal Of Pediatric Psychology, 2011 May; 36(4), p. 438-50.
PMID: 21097489
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Regional White Matter Anisotropy And Reading Ability In Patients Treated For Pediatric Embryonal Tumors
Authors: Palmer S.L. , Reddick W.E. , Glass J.O. , Ogg R. , Patay Z. , Wallace D. , Gajjar A. .
Source: Brain Imaging And Behavior, 2010 Jun; 4(2), p. 132-40.
PMID: 20502994
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Predicting Methylphenidate Response In Long-term Survivors Of Childhood Cancer: A Randomized, Double-blind, Placebo-controlled, Crossover Trial
Authors: Conklin H.M. , Helton S. , Ashford J. , Mulhern R.K. , Reddick W.E. , Brown R. , Bonner M. , Jasper B.W. , Wu S. , Xiong X. , et al. .
Source: Journal Of Pediatric Psychology, 2010 Mar; 35(2), p. 144-55.
PMID: 19465537
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Acute Neurocognitive Response To Methylphenidate Among Survivors Of Childhood Cancer: A Randomized, Double-blind, Cross-over Trial
Authors: Conklin H.M. , Khan R.B. , Reddick W.E. , Helton S. , Brown R. , Howard S.C. , Bonner M. , Christensen R. , Wu S. , Xiong X. , et al. .
Source: Journal Of Pediatric Psychology, 2007 Oct; 32(9), p. 1127-39.
PMID: 17569711
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Factor Analysis And Validity Of The Conners Parent And Teacher Rating Scales In Childhood Cancer Survivors
Authors: Helton S.C. , Corwyn R.F. , Bonner M.J. , Brown R.T. , Mulhern R.K. .
Source: Journal Of Pediatric Psychology, 2006 Mar; 31(2), p. 200-8.
PMID: 16467320
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Smaller White-matter Volumes Are Associated With Larger Deficits In Attention And Learning Among Long-term Survivors Of Acute Lymphoblastic Leukemia
Authors: Reddick W.E. , Shan Z.Y. , Glass J.O. , Helton S. , Xiong X. , Wu S. , Bonner M.J. , Howard S.C. , Christensen R. , Khan R.B. , et al. .
Source: Cancer, 2006-02-15 00:00:00.0; 106(4), p. 941-9.
PMID: 16411228
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Short-term Efficacy Of Methylphenidate: A Randomized, Double-blind, Placebo-controlled Trial Among Survivors Of Childhood Cancer
Authors: Mulhern R.K. , Khan R.B. , Kaplan S. , Helton S. , Christensen R. , Bonner M. , Brown R. , Xiong X. , Wu S. , Gururangan S. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2004-12-01 00:00:00.0; 22(23), p. 4795-803.
PMID: 15570081
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Attentional Functioning And White Matter Integrity Among Survivors Of Malignant Brain Tumors Of Childhood
Authors: Mulhern R.K. , White H.A. , Glass J.O. , Kun L.E. , Leigh L. , Thompson S.J. , Reddick W.E. .
Source: Journal Of The International Neuropsychological Society : Jins, 2004 Mar; 10(2), p. 180-9.
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