Slight cognitive impairment and magnetic resonance imaging abnormalities but normal school levels in children treated for acute lymphoblastic leukemia with chemotherapy only

Kingma, Annette; Dommelen, Rieneke I. van; Mooyaart, Eduard L.; Wilmink, J. T.; Deelman, B.G.; Kamps, Willem A.

doi:10.1067/mpd.2001.117066

Cited by 102 publications

(117 citation statements)

References 28 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…CNSdirected chemotherapy for ALL, consisting of intrathecal methotrexate, alone or in combination with cytarabine and corticosteroids, and of systemic methotrexate and corticosteroids, is associated with central neurotoxicity (Kerr et al, 2001;Surtees et al, 1998). Various studies have demonstrated visuomotor deficits in relationship with other cognitive impairments in children with ALL after treatment with chemotherapy only (Copeland et al, 1996;Kingma et al, 2001;Lesnik et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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

Buizer

Sonneville

Heuvel‐Eibrink

et al. 2005

J. Inter. Neuropsych. Soc.

View full text Add to dashboard Cite

Treatment for childhood acute lymphoblastic leukemia (ALL), which includes CNS prophylaxis, is associated with central and peripheral neurotoxicity. The purpose of the present study was to analyze the effects of chemotherapy on various levels of visuomotor control in survivors of childhood ALL treated without cranial irradiation, and to identify risk factors for possible deficits. Visuomotor function was compared between children after treatment for ALL (n 5 34), children after treatment for Wilms tumor, which consists of non-CNS directed chemotherapy (n 5 38), and healthy controls (n 5 151). Three tasks were administered: a simple visual reaction time task and two tasks measuring visuomotor control with one requiring a higher level of cognitive control than the other. Visuomotor deficits were detected only in the ALL group, with poorer performance restricted to the condition requiring the highest level of control. Significant risk factors for poorer performance were female gender and a short time since end of treatment, and a trend was found for a young age at diagnosis. A high cumulative methotrexate dose was an adverse predictive factor in girls. The results indicate that chemotherapy-induced central neurotoxicity in childhood ALL treatment is associated with higher order visuomotor control deficits. Girls appear to be particularly vulnerable. (JINS, 2005, 11, 554-565.)

show abstract

Section: Introductionmentioning

confidence: 99%

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

Buizer

Sonneville

Heuvel‐Eibrink

et al. 2005

J. Inter. Neuropsych. Soc.

View full text Add to dashboard Cite

show abstract

“…Impairments in attention, mental flexibility, concentration, visual memory, and speed of information processing are estimated in some studies to occur in 4-75% of breast cancer patients who receive adjuvant chemotherapy and to persist even years after completion of the therapy (Ahles and Saykin 2002;Kingma et al 2001;O'Shaughnessy 2002;Schagen et al 1999Schagen et al , 2001Schagen et al , 2002aSchagen et al , b, 2006Silberfarb et al 1980;Tchen et al 2003;van Dam et al 1998;Wieneke and Dienst 1995). In these studies, the cognitive impairments are attributed to the chemotherapy but not to anxiety, depression, fatigue, self-reported complaints of cognitive dysfunction (Schagen et al 2006;Schagen et al 1999), patient age, or menopausal status (Brezden et al 2000).…”

mentioning

confidence: 99%

Effects of chemotherapeutic agents 5-fluorouracil and methotrexate alone and combined in a mouse model of learning and memory

2008

View full text Add to dashboard Cite

Rationale-The concern that adjuvant cancer chemotherapy agents cause cognitive impairment in a significant number of patients has been expressed by patients and healthcare providers, but clinical studies have yielded conflicting results to date.Objective-We directly tested two commonly used chemotherapeutic agents in a mouse model of learning and memory.Materials and methods-In the present study, mice were conditioned to respond for a liquid reinforcer (Ensure solution) in the presence of an audible tone on day 1 as a measure of acquisition and were then required to perform the same response on day 2 as a measure of retrieval and retention. Methotrexate and 5-fluorouracil were administered prior to the day 1 session.Results-Methotrexate (1.0-32 mg/kg) alone failed to alter mean latency acquisition, retrieval, or reinforced response rates. Similar to scopolamine, a known amnesic in this assay, 5-fluorouracil (3-75 mg/kg) failed to alter response rates or acquisition latency on day 1 but significantly altered latency to retrieve a previously learned response on day 2. In combination, 3.2 mg/kg methotrexate plus 75 mg/kg 5-fluorouracil significantly increased day 1 and day 2 acquisition and retrieval latencies without altering responserates or motivation to respond as measured by progressive ratio responding. Conclusion-Takentogether, these data demonstrate that 5-fluorouracil causes increased latencies for retrieval of previously learned behavioral responses and that combination of chemotherapeutic agents may produce greater delays than either agent alone, including when neither agent alone does so.

show abstract

“…Four studies had a mean time since diagnosis of less than 6 years. 29,30,32,34 Most studies excluded ALL survivors with documented premorbid learning disabilities or other developmental conditions, such as Down syndrome. 11,[27][28][29][30][31]33 In most studies, healthy controls were selected from the surrounding community.…”

mentioning

confidence: 99%

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

Iyer

Balsamo

Bracken

et al. 2015

Blood

162

132

View full text Add to dashboard Cite

• Children treated for ALL without cranial radiation display significant IQ deficits of 6 to 8 points compared with healthy controls.• Moderate deficits occur in other neurocognitive domains including working memory, information processing speed, and fine motor functioning.Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with 5-year survival rates of ∼90% even after largely eliminating cranial radiation. This meta-analysis assesses the long-term neurocognitive functioning after chemotherapy-only regimens among survivors of childhood ALL. We conducted a systematic review to identify studies that evaluated long-term neurocognitive functioning following treatment of ALL by searching MEDLINE/PubMed, Database of Abstracts of Reviews of Effects, and secondary sources. Studies were included if ALL survivors were in continuous first remission, did not receive any radiation, were at least ‡2 years off therapy or ‡5 years since diagnosis, and were compared with a healthy control group. Weighted mean differences with 95% confidence intervals (CIs) were calculated. Ten nonexperimental studies met all eligibility criteria and included 509 patients and 555 controls. Meta-analysis demonstrated statistically significant moderate impairment across multiple neurocognitive domains evaluated, with intelligence most affected. Significant differences in standard deviation (SD) scores were found for Full Scale intelligence quotient (IQ) (20.52 SD; 95% CI, 20.68 to 20.37), Verbal IQ (20.54 SD; 95% CI, 20.69 to 20.40), and Performance IQ (20.41 SD; 95% CI, 20.56 to 20.27); these SD scores correspond to changes in IQ of 6 to 8 points. Working memory, information processing speed, and fine motor domains were moderately, but statistically significantly, impaired. Meta-analysis of ALL survivors treated without cranial radiation demonstrated significant impairment in IQ and other neurocognitive domains. Patients and their families should be informed about these potential negative effects to encourage surveillance and educational planning. Both preventive and intervention strategies are needed. (Blood. 2015;126(3):346-353) IntroductionAcute lymphoblastic leukemia (ALL) is the most common malignancy in children, accounting for 18% of all cancers and 74% of all leukemias.1 As a result of improvements in treatment and supportive care over recent decades, the current 5-year relative survival rate is 89% for children diagnosed with ALL before age 20 years 1 and exceeds 93% for children with standard risk features diagnosed before age 10 years.2 Because the vast majority of children with ALL are expected to survive their disease, it is important to understand the long-term burden of therapy.Neurocognitive and psychological difficulties as a result of chemotherapy have been documented in survivors of adult cancer across a variety of cancer types.3 However, most pediatric studies have focused on children with brain tumors or central nervous system (CNS)-directed radiation treatment. 4 Although the deleterious neurocognitive ...

show abstract

Slight cognitive impairment and magnetic resonance imaging abnormalities but normal school levels in children treated for acute lymphoblastic leukemia with chemotherapy only

Cited by 102 publications

References 28 publications

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

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

Effects of chemotherapeutic agents 5-fluorouracil and methotrexate alone and combined in a mouse model of learning and memory

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

Contact Info

Product

Resources

About