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Neuropsychological Effects of Cranial Irradiation in Young Children With Acute Lymphoblastic Leukemia 9 Months After Diagnosis
William E. MacLean, Jr, PhD;
Robert B. Noll, PhD;
James A. Stehbens, PhD;
Thomas A. Kaleita, PhD;
Edward Schwartz, PhD;
J. Kenneth Whitt, PhD;
Nancy L. Cantor, PhD;
Mary Waskerwitz, BSN, CPNP;
Fred Ruymann, MD;
Louis J. Novak, MD;
Austin Woodard, PsyD;
G. Denman Hammond, MD;
Children's Cancer Group
Arch Neurol. 1995;52(2):156-160.
Abstract
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Study Objective
To determine the effects of cranial irradiation on neuropsychological test performance evident 9 months after diagnosis.
Design
A companion study to a randomized clinical trial (CCG-105).
Setting
Institutions participating in Childrens Cancer Group cooperative treatment trials.
Patients
Seventy-four children aged 3.0 to 6.5 years with average-risk acute lymphoblastic leukemia. Children with central nervous system leukemia at the time of diagnosis, preexisting mental retardation, or Down's syndrome or for whom English was not the primary language were not eligible for study.
Interventions
Children were randomized to receive treatment with one of four systemic chemotherapy regimens and either intrathecal methotrexate sodium during induction and consolidation plus 18 Gy of cranial irradiation or intrathecal methotrexate during induction, consolidation, and maintenance as central nervous system prophylaxis.
Measurement and Results
The groups were comparable with regard to chronologic age, sex, and family socioeconomic status. Children who received cranial irradiation plus intrathecal methotrexate scored significantly lower on the McCarthy Motor Scale (P<.05) and the Token Test (P<.05) than children who received intrathecal methotrexate alone. The groups did not differ significantly on the McCarthy General Cognitive Index, Developmental Test of Visual Motor Integration, or Peabody Picture Vocabulary Test—Revised.
Conclusions
Findings suggest that the combined effects of cranial irradiation and intrathecal methotrexate therapy on neuropsychological performance may be evident in young children as early as 9 months after diagnosis. Follow-up assessment of these children will reveal whether these effects remain constant, intensify, or resolve.
Author Affiliations
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From the Department of Psychology and Human Development, Peabody College of Vanderbilt University, Nashville, Tenn (DrMacLean); the Department of Hematology-Oncology, Children's Hospital Medical Center, University of Cincinnati (Ohio) (Dr Noll); the Department of Pediatrics, University of Iowa, Iowa City (Dr Stehbens); the Department of Pediatrics, University of California-Los Angeles (Dr Kaleita); the Department of Pediatric Psychology, University of Michigan, Ann Arbor (Dr Schwartz); the Department of Psychiatry, University of North Carolina-Chapel Hill (Dr Whitt); the Department of Psychology, Primary Children's Medical Center, University of Utah, Salt Lake City (Dr Cantor); the Department of Pediatric Hematology-Oncology, Butterworth Hospital, Grand Rapids, Mich (Ms Waskerwitz); the Department of Pediatric Hematology-Oncology, Ohio State University, Columbus (Dr Ruymann); the Department of Radiology, Case Western Reserve University, Cleveland, Ohio (Dr Novak); the Department of Neuropsychology, University of Wisconsin, Madison (Dr Woodard); and the Department of Pediatrics, University of Southern California School of Medicine, Pasadena (Dr Hammond).
Footnotes
Accepted for publication November 24, 1993.
This investigation was supported by the Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Department of Health and Human Services.
The authors gratefully acknowledge the valued contributions of David Tubergen, MD, Gerald Gilchrist, MD, Harland Sather, PhD, Richard O'Brien, MD, and Lonnie Zeltzer, MD, and also Kathlene Fitzhugh-Bell, PhD, P'Nian Chang, PhD, Thomas Curtis, PhD, Judith Groves, PhD, Hilda Kwok, PhD, Ernie Katz, PhD, Robin Goodman, PhD, Eric Brown, PhD, Robert Weils, MD, Joan Bachman, PhD, Fred Theye, PhD, Wayne McDonald, PhD, M. Douglas Ris, PhD, Kenneth Tarnowski, PhD, and Keith Yeates, PhD, for their assistance with data collection.
Reprint requests to Childrens Cancer Group, PO Box 60012, Arcadia, CA 91066-6012 (Dr Hammond).
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