Cognitive Changes in Children Treated for Acute Lymphoblastic Leukemia With Chemotherapy Only According to the Pediatric Oncology Group 9605 Protocol

Abstract

The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Children's Hospital of Eastern Ontario. Mean age at diagnosis was 4.88 +/- 2.54 years. The mean (n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 +/- 15.69 and 84.83 +/- 19.11, respectively). Mean (n = 20) Verbal and Visual Memory Indexes of 82.95 +/- 15.46 and 88.30+/- 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity.

Neurodevelopmental sequelae of pediatric acute lymphoblastic leukemia and its treatment

“…Montour-Proulx et al [2005] reported leukoencephalopathy in 78% of 23 children treated on POG 9605. Acute WM abnormalities may be transient; in some cases, they improve significantly following completion of treatment [Harila-Saari et al, 1998;Reddick et al, 2005a,b].…”

“…Acute WM abnormalities may be transient; in some cases, they improve significantly following completion of treatment [Harila-Saari et al, 1998;Reddick et al, 2005a,b]. The instability of WM abnormalities results in poor correlations with neurocognitive findings in children on active treatment [Wilson et al, 1991;Montour-Proulx et al, 2005] and the implications of these early transient imaging abnormalities for long-term neurocognitive functioning are unknown.…”

Quantitative morphologic evaluation of magnetic resonance imaging during and after treatment of childhood leukemia

“…Both of these findings are consistent with our own experience in which acute neurologic toxicity is most often associated with IT-MTX, and chronic neurotoxicity such as decreased cognitive functioning is more likely associated with IV-MTX and LE. Montour-Proulx et al [84] found that children treated with chemotherapy alone on the POG9605 protocol experienced substantial adverse effects on intelligence and memory functioning: 78% of 23 subjects showed LE on at least one MR image.…”

Clinical trials in pediatric neuro-oncology: what is missing and how we can improve

“…In the pediatric brain tumor population, deficits seen with chemotherapy treatments are less than those seen with radiation. Nonetheless, specific chemotherapies such as methotrexate have previously demonstrated deleterious effects on neurocognition and chemotherapy, as a whole, has been linked to deficits in executive functioning, attention, visualmotor functioning, visual processing and overall IQ in children treated for leukemia [45,46,47]. Interestingly, a study done by Meyers and Hess, found that decreases in cognition preceded tumor progression on imaging in adult patients with brain tumors [48].…”