No Major Cognitive Impairment in Young Children With Acute Lymphoblastic Leukemia Using Chemotherapy Only: A Prospective Longitudinal Study

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

doi:10.1097/00043426-200202000-00010

Cited by 76 publications

(71 citation statements)

References 21 publications

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“…27,28,[31][32][33][34] The other 4 studies used a longitudinal design, identified patients at diagnosis, and completed periodic neurocognitive assessments during treatment and off therapy. 11,19,29,30 Collectively, the study population included in the analyses had a mean age at diagnosis of 4.4 years (median, 4.0), a mean age at last evaluation of 11.7 years (median, 10.3), and a mean time since diagnosis of 8.0 years (median, 8.2). Four studies had a mean time since diagnosis of less than 6 years.…”

Section: Resultsmentioning

confidence: 99%

“…Intelligence or overall cognitive ability was measured by 8 studies. 11,19,28,[30][31][32][33] IQ was measured and assessed across 3 dimensions of the Wechsler Intelligence Scales (version dependent on age of patient): FSIQ, VIQ, and PIQ. For FSIQ, 432 ALL survivors met eligibility to be included in the treatment group and were compared with 465 healthy control subjects.…”

Section: Resultsmentioning

confidence: 99%

“…4 Although the deleterious neurocognitive effects of cranial radiation in ALL patients have been well-documented, [5][6][7][8][9][10] upfront treatment of ALL now rarely involves cranial radiation and instead accomplishes CNS prophylaxis with systemic and intrathecal chemotherapy. 11,12 Results have varied on the negative effects of chemotherapy without radiation in pediatric cancer populations. [13][14][15] Individual studies in the past have shown some negative effects of treatment.…”

Section: Introductionmentioning

confidence: 99%

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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

163

132

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• 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 ...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

163

132

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“…Cranial radiation is associated with more severe neurocognitive impairment than that conferred by systemic and intrathecal chemotherapy. 20,[27][28][29] As previously discussed, our study overcame many of the limitations of the Waber et al study. 26 Our overall results are consistent with smaller studies based on patients with ALL.…”

Section: Discussionmentioning

confidence: 96%

A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia

Kadan‐Lottick

Brouwers

Breiger

et al. 2009

Blood

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In previous clinical trials of childhood acute lymphoblastic leukemia (ALL), dexamethasone resulted in higher event-free survival rates than prednisone, presumably due to greater central nervous system penetration. Dexamethasone's association with long-term neurocognitive toxicity is unknown. In this multisite study, we measured neurocognitive functioning in 92 children with standard-risk ALL, 1 to 9.99 years at diagnosis, at a mean of 9.8 years after randomization to prednisone (n ‫؍‬ 41) or dexamethasone (n ‫؍‬ 51) on Children's Cancer Group (CCG) 1922. No significant overall differences in mean neurocognitive and academic performance scores were found between the prednisone and dexamethasone groups after adjusting for age, sex, and time since diagnosis. The exception was that patients receiving dexamethasone scored one-third of a standard deviation worse on word reading (98.8 ؎ 1.7 vs 104.9 ؎ 1.8; P ‫؍‬ .02). There were no group differences in the distribution of test scores or the parents' report of neurologic complications, psychotropic drug use, and special education. Further analyses suggested for the dexamethasone group, older age of diagnosis was associated with worse neurocognitive functioning; for the prednisone group, younger age at diagnosis was associated with worse functioning. In conclusion, our study did not demonstrate any meaningful differences in long-term cognitive functioning of childhood ALL patients based on corticosteroid randomization. This study is registered with http://www. clinicaltrials.gov under NCT00085176. IntroductionCorticosteroids have long been recognized as an important component of therapy for childhood acute lymphoblastic leukemia (ALL). More recently, randomized control clinical trials have established a therapeutic benefit of dexamethasone over prednisone. In the Children's Cancer Group (CCG) 1922 trial of 1060 patients, Bostrom et al concluded that patients randomized to dexamethasone had a 6-year event-free survival of 85% plus or minus 2% compared with 77% plus or minus 2% for those randomized to prednisone (P ϭ .002). 1 Patients randomized to dexamethasone had a lower rate of both isolated central nervous system (CNS) and bone marrow relapse. These results are consistent with those found by most other cooperative groups. 2-4 Dexamethasone's therapeutic advantage is thought to be, in part, due to its better CNS penetration. 5 The recently completed CCG 1991 trial reported event-free survival rates approaching 90% and overall survival rates of approximately 95% for standard-risk ALL patients, who were nonrandomly treated with dexamethasone. 6 Therefore, the effect of different therapies on future quality of life has increasingly been considered as a critical factor in the selection of optimal treatment. Multiple previous studies of long-term survivors of childhood ALL, even those who did not receive cranial radiation, 7-12 have identified deficits in neurocognitive function that might impair quality of life. Among others, investigators have consistently identified di...

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“…Kingma et al found normal cognitive functioning but "lower test scores in patients compared with controls in the test of attention, speed, sequencing, mental flexibility, and visual search" (8). Lofstad et al found that even though "the cognitive outcome for children with ALL treated with chemotherapy only was in the normal range, it represented a substantial decrease of as much as one standard deviation compared to matched healthy controls" (9).…”

Section: Introductionmentioning

confidence: 99%

Neurodevelopmental Outcome of Childhood Cancer Survivors Treated at the Eric Williams Medical Sciences Complex

2014

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No Major Cognitive Impairment in Young Children With Acute Lymphoblastic Leukemia Using Chemotherapy Only: A Prospective Longitudinal Study

Abstract: Children surviving ALL have no major cognitive impairment after chemotherapy, including intrathecal and high-dose intravenous methotrexate. The slightly better outcome in the current group may indicate possible adverse effects of more dexamethasone treatment in the previous group.

Cited by 76 publications

References 21 publications

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

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

A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia

Neurodevelopmental Outcome of Childhood Cancer Survivors Treated at the Eric Williams Medical Sciences Complex

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