Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.

Abstract

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.

Cognitive and psychosocial functioning of pediatric hematopoietic stem cell transplant patients: A prospective longitudinal study

“…44 Many of the children in this study were diagnosed with ALL and had undergone intensive systemic and intrathecal chemotherapy, which has been identified as a risk factor for neurocognitive problems in children with ALL. [1][2][3][4][5][6]44 Mental arithmetic requires both attention and short-term memory, also abilities that can be affected by CNS treatment.…”

“…Due to the lack of sufficient data from pediatric GSCT patients, the suspected impact of treatment on cognitive functioning has been extrapolated from other diseases and treatments, ie cranial irradiation and chemotherapy for acute lymphocytic leukemia (ALL) or CNS tumors, [1][2][3][4][5][6] the effects of which were demonstrated to be dose-and agerelated. It has been hypothesized that pre-HSCT conditioning regimens, including total body irradiation (TBI) have a detrimental effect on children undergoing HSCT.…”

Methotrexate‐associated alterations of the folate and methyl‐transfer pathway in the CSF of ALL patients with and without symptoms of neurotoxicity

“…Severe leukoencephalopathy was associated with demyelination [2]. Moreover, children treated with MTX may develop learning disabilities and a decreased intelligence quotient [12][13][14].…”

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

“…This has resulted in an increasing interest in the late effects of disease and treatment on physical, mental and social well-being of the survivors. Several elements of therapy for ALL may affect the function of the central and peripheral nervous system, and cognitive deficits (e.g., Anderson et al, 2000;Brown et al, 1992;Butler et al, 1994;Moleski, 2000;Ochs et al, 1991) as well as gross and fine motor impairments (Galea et al, 2004;HarilaSaari et al, 2001;Lehtinen et al, 2002;Reinders-Messelink et al, 1996;Vainionpaa, 1993;Wright et al, 1998) have been reported in survivors of childhood ALL. CNS-directed treatment is a standard component of therapy for ALL.…”