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Neuropsychological Outcome in Chemotherapy-Only–Treated Children With Acute Lymphoblastic Leukemia

Nathalie C.A.J. Jansen, Annette Kingma, Arnout Schuitema, Anke Bouma, Anjo J.P. Veerman, Willem A. Kamps

From the Department of Pediatric Hematology Oncology, Beatrix Children's Hospital, University Medical Center Groningen, and Department of Clinical and Developmental Psychology, University of Groningen; Department of Pediatric Psychology, University Medical Center Utrecht, Utrecht; Department of Pediatrics, Free University Medical Center, Amsterdam; and the Dutch Childhood Oncology Group, the Hague, the Netherlands

Corresponding author: Nathalie C.A.J. Jansen, MSc, Beatrix Children's Hospital Groningen, Department of Pediatric Hematology Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30 001, 9700 RB Groningen, the Netherlands; e-mail: N.C.A.Jansen{at}umcutrecht.nl

Purpose To evaluate neuropsychological functioning over time in children treated for acute lymphoblastic leukemia (ALL) with chemotherapy only.

Patients and Methods Forty-nine consecutive patients (median age at first assessment, 6.8 years; range, 4.0 to 11.8 years) treated with intrathecal and systemic chemotherapy were included in a nationwide, prospective-longitudinal, sibling-controlled study. Patients and siblings completed three extensive neuropsychological assessments: at diagnosis, 3 to 6 months after completion of (2-year) treatment and 4.5 years after diagnosis. Assessments included measures of learning, memory, attention, speed, executive functioning, visual-constructive functioning, and fine-motor functioning. Multilevel analyses were applied to evaluate patients' performances over time and to compare patients to 29 siblings (median age of siblings at first assessment, 8.2 years; range, 4.5 to 12.6 years) and to normative data.

Results No major differences were found in neuropsychological performance between patients and siblings, with both groups performing mainly in the normal range. The patient group as a whole, however, scored significantly lower than the siblings on complex fine-motor functioning at the last evaluation. Large practice effects were found for both patients and siblings in four of 11 tasks. Patients who uttered physical complaints (ie, pain and/or tiredness) at the first pretreatment assessment scored significantly lower than siblings on attention and speed at the last two evaluations.

Conclusion Despite intensive and potentially neurotoxic treatment, no evident negative, neuropsychological late effects were found 4.5 years after diagnosis, except for effects on complex fine-motor functioning. Both the large practice effects observed and the poorer performances on sustained attention for patients with physical complaints should be reckoned with in prospective, longitudinal neuropsychological research in children.

Supported in part by Grant No. RUG 1998-1737 from the Dutch Cancer Society.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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