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

Abstract

This meta-analysis assesses cognitive functioning in children with acute lymphoblastic leukemia post-treatment who were treated with either chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). The databases Pubmed and PsychInfo were searched between 1-1-2000and 31-12-2021. Data were analyzed using Comprehensive Meta-Analysis (version 2). 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). 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, long-term clinical follow-up of neurocognitive development may be prudent to detect possible (late) neurocognitive effects.