No lasting neuropsychological effects of chemotherapy for ALL in children

July 7, 2008

NEW YORK (Reuters Health) - Two years after the end of potentially neurotoxic intrathecal and systemic chemotherapy, no major differences in neuropsychological outcome were found between pediatric patients with acute lymphoblastic leukemia (ALL) and their healthy siblings. The only significant difference was in complex fine-motor functioning, where the patient group scored lower, according to a report by Dutch researchers in the June 20 issue of the Journal of Clinical Oncology.

The study involved 49 patients aged 4.0-11.8 years (median 6.8 years) at baseline, and 28 healthy siblings aged 4.9-12.6 years (median 8.2 years). Both groups were free of pre-existing disorders that might interfere with normal cognitive development.

Using a standard Dutch protocol, patients were treated with chemotherapy only, including vincristine, dexamethasone, daunorubicine with high-dose methotrexate, leucovorin rescue and triple intrathecal therapy as CNS prophylaxis. Total duration of treatment was 108 weeks.

The first of three neuropsychological assessments was done shortly after diagnosis and no more than 2 weeks after the start of chemotherapy. The second was done 3 to 6 months after the end of therapy, and the third was done 4.5 years after diagnosis (median 2.2 years after the end of therapy).

The intensive neuropsychological assessments evaluated performance on 11 tasks in 4 categories: learning and memory, sustained attention and speed, executive functioning, and visual-motor and fine-motor functioning.

No significant differences were found between patients and siblings for learning and memory, sustained attention and speed, or executive functioning. At the final assessment, however, patients scored significantly lower than siblings on complex fine-motor functioning.

The researchers, who were led by Nathalie C.A.J. Jansen of the University of Groningen, noted that children who missed more than 2 tests at the initial assessment because of physical complaints (such as pain or tiredness) scored significantly lower than their siblings on attention and speed at the later two assessments.

"We hypothesize that these patients have reduced cognitive reserve capacity," the authors write. "If true, the speed and attention task should be attempted at baseline; those patients who cannot complete it because of physical complaints are those who should be considered at risk for mild impairment."

The researchers also found large practice effects for both patients and siblings.