The purpose of this study is to test a math intervention for children diagnosed with acute lymphoblastic leukemia (ALL) who receive triple intrathecal chemotherapy and systemic intermediate dose methotrexate according to Pediatric Oncology Group (POG) protocols. Despite increasing evidence of academic difficulties in children successfully treated for ALL, there are no reports of intervention studies. The primary aim of this study is to determine if a math intervention can prevent a significant decline in math achievement in children with ALL who receive triple intrathecal therapy and systemic intermediate dose methotrexate. One hundred and twenty children (4-10 years of age) with ALL recruited from two POG institutions will be randomly assigned to Standard Care or to a Math Intervention. It is hypothesized that there will be a greater decline in math achievement scores in the Standard Care group than in the Math Intervention group.
The second aim i s to determine the nature of the decline in math skills associated with triple intrathecal therapy. Three classes of variables will be examined: (1) The concentration of four phospholipids in cerebral spinal fluid (CSF): sphingomyelin, phosphatidylcholine, lysophosphatidylcholine and cardiolipin; (2) Other cognitive abilities that may be related to math achievement; and (3) Characteristics of the child: age at time of diagnosis, sex, number of school absences, socioeconomic status and baseline performance on academic and cognitive measures. A longitudinal prospective design with four evaluations of math and language achievement and cognitive abilities is proposed. The concentration of phospholipids, a biological marker of CNS injury, will be measured in CSF samples collected when lumbar punctures are done for intrathecal therapy. A comparison group of healthy children will be included to provide an estimate of the effects of repeated testing and to estimate losses in cognitive abilities associated with ALL treatment. Data will be analyzed in a two-step process aimed at developing measurement models and output will be used in subsequent analyses, including structural equation models. Measurement models will be established by confirmatory factor analysis. Child Characteristics will also be evaluated (as moderator variables). Individual growth curves for each child will be used in models. Long-term disease free survival from ALL is 80% because of aggressive systemic and CNS therapy. Pediatric oncology nurses manage acute and long-term toxicities of treatment. The proposed study addresses the cognitive and academic sequelae associated with CNS treatment, and to our knowledge is the first randomized intervention trial designed to prevent minimize math deficits in children receiving ALL treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR004905-05
Application #
6704755
Study Section
Nursing Research Study Section (NURS)
Program Officer
Hare, Martha L
Project Start
2000-06-01
Project End
2006-10-31
Budget Start
2004-03-01
Budget End
2006-10-31
Support Year
5
Fiscal Year
2004
Total Cost
$537,575
Indirect Cost
Name
University of Arizona
Department
Type
Schools of Nursing
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
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Moore, Ida M; Hockenberry, Marilyn J; Anhalt, Cynthia et al. (2012) Mathematics intervention for prevention of neurocognitive deficits in childhood leukemia. Pediatr Blood Cancer 59:278-84
Stenzel, Stephanie L; Krull, Kevin R; Hockenberry, Marilyn et al. (2010) Oxidative stress and neurobehavioral problems in pediatric acute lymphoblastic leukemia patients undergoing chemotherapy. J Pediatr Hematol Oncol 32:113-8
Caron, Joshua E; Krull, Kevin R; Hockenberry, Marilyn et al. (2009) Oxidative stress and executive function in children receiving chemotherapy for acute lymphoblastic leukemia. Pediatr Blood Cancer 53:551-6
Moore, Ida M Ki; Miketova, Petra; Hockenberry, Marilyn et al. (2008) Methotrexate-induced alterations in beta-oxidation correlate with cognitive abilities in children with acute lymphoblastic leukemia. Biol Res Nurs 9:311-9
Carey, Marissa E; Hockenberry, Marilyn J; Moore, Ida M et al. (2007) Brief report: effect of intravenous methotrexate dose and infusion rate on neuropsychological function one year after diagnosis of acute lymphoblastic leukemia. J Pediatr Psychol 32:189-93
Kaemingk, Kris L; Carey, Marissa E; Moore, Ida M et al. (2004) Math weaknesses in survivors of acute lymphoblastic leukemia compared to healthy children. Child Neuropsychol 10:14-23
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