A meta‐analysis of the neuropsychological sequelae of chemotherapy‐only treatment for pediatric acute lymphoblastic leukemia

Peterson, Catherine; Johnson, Courtney E.; Ramirez, Lisa; Huestis, Samantha; Pai, Ahna L. H.; Demaree, Heath A.; Drotar, Dennis

doi:10.1002/pbc.21544

Cited by 159 publications

(173 citation statements)

References 31 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…Our findings are consistent with those of a recently published study that found over 90% of Latino parents of childhood cancer survivors expressed interest in a culturally competent intervention aimed at reducing neurocognitive late effects [9]. Our intervention is based on the premise that neurocognitive assessment should be a standard component of survivorship care for at-risk patients, and that it plays a crucial role in addressing immediate school needs, as well as longer-term educational, vocational, and employment outcomes [2][3][4]10]. We believe that the critical ingredient of our approach is its culturally competent design and implementation (Table S1), which includes a culturally and linguistically competent psychologist.…”

Section: Discussionsupporting

confidence: 80%

“…Although approximately 90% of patients become long-term survivors, up to 40% may develop treatment-related neurocognitive dysfunction that impairs learning and school performance [1][2][3]. Consequently, routine neuropsychological screening is recommended by the Children's Oncology Group (COG Long-Term Follow-Up Guidelines) for all childhood ALL survivors [4].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A parent‐directed intervention for addressing academic risk in Latino survivors of childhood leukemia: results of a pilot study

et al. 2016

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

A parent‐directed intervention for addressing academic risk in Latino survivors of childhood leukemia: results of a pilot study

et al. 2016

View full text Add to dashboard Cite

“…[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.…”

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

163

140

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

“…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][8][9][10][11][12] have identified deficits in neurocognitive function that might impair quality of life. Among others, investigators have consistently identified difficulties in attention, working memory, processing speed, mathematics, and visual motor integration, but the exact etiologic factors of these deficits have not yet been established.…”

Section: Introductionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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...

show abstract

A meta‐analysis of the neuropsychological sequelae of chemotherapy‐only treatment for pediatric acute lymphoblastic leukemia

Abstract: Results support the presence of neuropsychological and academic sequelae for ALL survivors treated solely with chemotherapy and highlight the need for ongoing follow-up of children with ALL using a standardized neuropsychological test battery and research methodology.

Cited by 159 publications

References 31 publications

A parent‐directed intervention for addressing academic risk in Latino survivors of childhood leukemia: results of a pilot study

A parent‐directed intervention for addressing academic risk in Latino survivors of childhood leukemia: results of a pilot study

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

Contact Info

Product

Resources

About