Cognitive Effects of Childhood Leukemia Therapy: A Case for Four Specific Deficits

Abstract

Prophylactic treatment of the central nervous system (CNS) with cranial irradiation and antineoplastic drugs has made childhood acute lymphoblastic leukemia (ALL) a survivable disease, but at the same time there have been many reports of iatrogenic effects, including deficits in cognitive functioning. Previous research suggests a particular effect on the Freedom from Distractibility factor of the WISC-R, memory, and attention. These particular abilities are tested in a group of 43 ALL survivors, with comparisons against solid tumor as well as sibling controls. The results indicate that four cognitive processes are affected by CNS prophylaxis for ALL: short-term memory, speed of processing, visuomotor coordination, and sequencing ability. Younger children have a more severe speed of processing deficit and children treated with a less rigorous protocol appear to be slightly less affected generally. The specific cognitive deficits found are related to neurological evidence on both theoretical and empirical grounds. Results suggest that children who have received CNS prophylaxis are able to learn, but may be slower to acquire new material and may benefit from bimodal presentation.

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

“…The emerging consensus is that the substantial decline in IQ and academic achievement observed in childhood cancer survivors is the result of one or more cognitive-processing deficits involving attention, short-term memory, speed of processing, visuomotor coordination, or sequencing abilities [16,[87][88][89][90]. Some of the most convincing evidence for these specific deficits has come from the work of Brouwers et al [16,91], who conducted two studies using both neuropsychologic testing and CT or MR neuroimaging to evaluate long-term survivors of childhood ALL treated with chemotherapy and cranial irradiation.…”

Comparing attentional skills in children with acquired and developmental central nervous system disorders

“…Studies reporting on children treated with a combination of cranial irradiation and chemotherapy, document slowed processing speed and deficits in selective attention Cousens et al, 1988). In contrast, sustained and shifting attention skills appear to be spared (Anderson et al, 2004a;Goff et al, 1980).…”

Abstracts 2009

“…Early reports of neurocognitive outcome in the absence of CRT also describe impairment in non-verbal function and academic achievement [19,20] with specific deficits in four primary areas of function: short-term memory, processing speed, visuomotor coordination, and sequencing ability [21,22] . Comparisons of neurocognitive outcomes among children treated with or without CRT generally find evidence of neurocognitive dysfunction in children who did and did not receive CRT though the risk is greater with CRT [12] .…”

“…In vitro studies of BRCA1 deficiency, whether through inherited mutation or down-regulation BRCA1, reported increased sensitivity to DNA-damaging agents[17][18][19][20][21][22][23][24] . For example, antisense inhibition of BRCA1 in cisplatinresistant SKOV3 ovarian cancer cells dramatically sensitized these cells by disruption of BRCA1-dependent DNA repair 26 .…”

“…For example, antisense inhibition of BRCA1 in cisplatinresistant SKOV3 ovarian cancer cells dramatically sensitized these cells by disruption of BRCA1-dependent DNA repair 26 . Overexpression of BRCA1 in ID8 murine ovarian cancer cells reduced sensitivity to cisplatin and other DNA-damaging agents 27 .In contrast to the increased sensitivity to DNA damage-based chemotherapy, increased resistance to antimicrotubule (paclitaxel) agents was observed in BRCA1-deficient cells[18][19][20][21][22][23] . All the above suggest that BRCA mutation could be a predictor for survival in patients with advanced ovarian carcinoma 25 , probably due to the increased benefit fromplatinum-based chemotherapy and possible different response to other chemotherapies.…”