Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia

Authors

  • Wilburn E. Reddick Ph.D.,

    Corresponding author
    1. Division of Translational Imaging Research, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Departments of Electrical and Computer Engineering and Biomedical Engineering, University of Memphis; Memphis, Tennessee
    • Division of Translational Imaging Research (MS 210), Department of Radiological Sciences, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105-2794
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    • Fax: (901) 495-5706

  • Zuyao Y. Shan Ph.D.,

    1. Division of Translational Imaging Research, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • John O. Glass M.S.,

    1. Division of Translational Imaging Research, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Susan Helton Ed.S.,

    1. Division of Behavioral Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Xiaoping Xiong Ph.D.,

    1. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Shengjie Wu M.S.,

    1. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Melanie J. Bonner Ph.D.,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina
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  • Scott C. Howard M.D.,

    1. Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee
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  • Robbin Christensen B.S.,

    1. Pharmaceutical Services, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Raja B. Khan M.D.,

    1. Division of Neurology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee
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  • Ching-Hon Pui M.D.,

    1. Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Raymond K. Mulhern Ph.D.

    1. Division of Behavioral Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee
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    • Deceased.


  • The authors dedicate this article to Raymond K. Mulhern.

Abstract

BACKGROUND

The primary objective of this study was to test the hypothesis that survivors of childhood acute lymphoblastic leukemia (ALL) have deficits in neurocognitive performance, and smaller white-matter volumes are associated with these deficits.

METHODS

The patients studied included 112 ALL survivors (84 patients who had received chemotherapy only, 28 patients who had received chemotherapy and irradiation; 63 males, 49 females; mean age ± standard deviation, 4.1 yrs ± 2.6 yrs at diagnosis; mean ± standard deviation yrs since diagnosis, 6.0 ± 3.5 yrs), and 33 healthy siblings who participated as a control group. Neurocognitive tests of attention, intelligence, and academic achievement were performed; and magnetic resonance images were obtained and subsequently were segmented to yield tissue volume measurements. Comparisons of neurocognitive measures and tissue volumes between groups were performed, and the correlations between volumes and neurocognitive performance measures were assessed.

RESULTS

Most performance measures demonstrated statistically significant differences from the normative test scores, but only attention measures exceeded 1.0 standard deviation from normal. Patients who had received chemotherapy alone had significantly larger volumes of white matter than patients who had received treatment that also included cranial irradiation, but their volumes remained significantly smaller than the volumes in the control group. Smaller white-matter volumes were associated significantly with larger deficits in attention, intelligence, and academic achievement.

CONCLUSIONS

Survivors of childhood ALL had significant deficits in attention and smaller white-matter volumes that were associated directly with impaired neurocognitive performance. Cranial irradiation exacerbated these deficits. Cancer 2006. © 2006 American Cancer Society.

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