Effects of chemotherapy on neurocognitive function in children with acute lymphoblastic leukemia: A critical review of the literature

Abstract

Chemotherapy-only treatment has increasingly become the standard of treatment for childhood acute lymphoblastic leukemia (ALL). The objective of this review is to assess the present state of knowledge of the neurocognitive effects of central nervous system (CNS)-directed chemotherapy in children with ALL, and to formulate directions for future research. We performed a review of studies published since 1997, that included an ALL group treated with chemotherapy only and a control group. Twenty-one studies met our inclusion criteria. There is evidence of subtle long-term neurocognitive deficits survivors of childhood ALL after treatment with chemotherapy only. These involve mainly processes of attention and of executive functioning, while global intellectual function is relatively preserved. Young age at diagnosis and female sex emerged as risk factors.

Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis

“…11-14 Conclusions from systematic reviews have been mixed, [16][17][18] largely because of reliance on qualitative methods to assess outcomes 18 and inclusion of studies with patients who had very recently completed therapy or without a control population. [16][17][18] Because neurocognitive impairment takes time to develop and/or be detected, early assessments are likely not adequate.…”

“…[16][17][18] Because neurocognitive impairment takes time to develop and/or be detected, early assessments are likely not adequate. Furthermore, because many of these neurocognitive measures are correlated with demographic factors, such as socioeconomic status, comparison with an appropriate healthy control group is particularly important.…”

“…[13][14][15] Individual studies in the past have shown some negative effects of treatment. However, most of these studies were hindered by small sample size and lack of appropriate controls, which makes it challenging to interpret and generalize their findings.11-14 Conclusions from systematic reviews have been mixed, [16][17][18] largely because of reliance on qualitative methods to assess outcomes 18 and inclusion of studies with patients who had very recently completed therapy or without a control population. [16][17][18] Because neurocognitive impairment takes time to develop and/or be detected, early assessments are likely not adequate.…”

Anticancer chemotherapy in teenagers and young adults: managing long term side effects

“…40 Antimetabolites and anthracyclines have been implicated. Although the association has long been established in childhood cancers, 41 emerging evidence shows a similar effect in TYAs. A retrospective study of more than 2500 cancer patients aged 11-21 identified deficiencies in emotional regulation, memory and task efficiency.…”

Neuropsychiatric aspects of paediatric brain tumours: an update

“…Methotrexate is known to interfere with folate metabolism resulting in demyelination and other toxic effects on CNS thereby leading to cognitive decline. (67) Problems that are reported with the use of chemotherapy in treatment of pediatric brain tumors are problems with sustained attention, which correlated with teacher reports of poorer academic performance, particularly in mathematics, increased internalizing behaviors on the Child Behavior Checklist, a parent report measure of social competence and behavior problems, visual processing, visual-motor functioning, attention and executive functioning, academic performance, verbal abilities, and memory with female gender and young age (particularly less than age 3 years) as risk factors. (68-70) Psychopharmacological and palliative care interventions for neurocognitive effects:…”