Effect of chemotherapy (with and without radiotherapy) on the intelligence of children and adolescents treated for acute lymphoblastic leukemia; a meta‐analysis

Abstract

Objective: This meta-analysis assesses cognitive functioning in children with acute lymphoblastic leukemia post-treatment who were treated with either chemotherapyonly (CT-only) or in combination with radiation therapy (CTRT). Methods:The databases Pubmed and PsychInfo were searched between 1-1-2000 and 31-12-2021. Data were analyzed using Comprehensive Meta-Analysis (version 2).Results: Mean weighted intelligence after treatment was 100.2 (number of studies n = 51, 95% CI: 98.8-101.5). For CT-only, it was 100.8 (95% CI: 99.5-102.2) and for CTRT 97.8 (95% CI: 95.9-100.2). Compared to recruited healthy controls, treated children had on average lower IQ scores (n = 23, mean difference −7.8, 95% CI: −10.7 to −5.0, p < 0.001). When looking only at studies using controls recruited from the patient's family, results remained significant (n = 5, mean difference −6.0, 95% CI: −8.6 to −3.5, p = 0.001). Meta-regressions aimed at identifying predictors of IQ after treatment failed to find an effect for sex or age. We could demonstrate an effect of time between diagnosis and IQ measurement for the CTRT treated patient (B = −0.26, 95% CI: −0.40 to −0.1, p = 0.002).Conclusions: IQ scores of patients treated with CT-only or CTRT treatment regimens did not differ from the normative population. However, compared to recruited control groups, patients showed lower mean IQ scores. The Flynn effect and/or selection effects may play a role in this discrepancy. Considering time since diagnosis may have a significant impact on IQ, at least in CTRT treated patients, longterm clinical follow-up of neurocognitive development may be prudent to detect possible (late) neurocognitive effects.

Cumulative Dosage of Intrathecal Chemotherapy Agents Predicts White Matter Integrity in Long-Term Survivors of Acute Lymphoblastic Leukemia: A PETALE Study

“…Our control group was matched for the level of education attained, the age at the time of the study, and sex. A common bias in studies of the neurocognitive status of ALL survivors is the control group, which tends to have an average IQ higher than the mean IQ of the normative population (100) [ 82 ]. Our recruitment efforts have allowed us to form a control group that has an average IQ of 104.9, which does not differ significantly from the normative population mean of 100 ( t (20) = 1.622, p = 0.121).…”