Cognitive function of children and adolescent survivors of acute lymphoblastic leukemia: A meta-analysis

Abstract

Pediatric cancer and its treatment may have an impact on the neurocognitive functions of childhood cancer survivors (CCS). The aim of the present meta-analysis was to compare the intelligence quotient (IQ) scores between CCS of acute lymphoblastic leukemia (ALL) and controls. A comprehensive electronic search identified original research articles that reported scores of the Wechsler Intelligence Scale (WISC; WISC-III, WISC-IV and WISC-R) for children and adolescents, aged 6-16 years at evaluation, survivors of ALL and healthy controls. The included CCS had completed anticancer treatment and were in remission at the time of assessment. A total of 16 studies were included in the meta-analysis, out of 128 extracted studies, and involved a total of 1,676 children and adolescents: 991 CCS (ALL) and 685 healthy controls. Among the studies, a random effects model revealed a moderate estimate of effect size [standardized mean difference (SMD), -0.78; 95% CI, -1.05 to -0.50], indicating that the WISC scores for total IQ were significantly lower in the CCS than in the controls. The mean total IQ range was 85.2-107.2 in the CCS and 88.4-114.1 in the controls. The difference in the mean total IQ between controls and CCS ranged from -13.8 to 20.6. As regards the WISC scores for verbal IQ, 11 studies were included. A random effects model revealed a moderate estimate of effect size (SMD, -0.71; 95% CI, -1.05 to -0.38), indicating that the WISC scores for verbal IQ were significantly lower in the CCS than in the controls. Among the 9 studies that had available data for performance IQ scores, a fixed effect model revealed a moderate estimate of effect size (SMD, -0.80; 95% CI, -1.09 to -0.52), indicating that the WISC scores for performance IQ were significantly lower in the CCS than in the controls. As the survival rates of children and adolescents with ALL are steadily increasing, regular, lifelong follow-up for neurocognitive late effects is imperative in order to improve their education and employment prospects and overall, their quality of life.

Keywords: IQ; WISC; acute lymphoblastic leukemia; adolescents; cancer; chemotherapy; children; cognitive; education; intelligence; learning difficulties; radiotherapy; survivors.

Figure 1.

PRISMA flow chart of study selection. PRISMA, preferred reporting items for systematic reviews and meta-analyses.

Figure 2.

Forest plot presenting the meta-analysis based on SMDs for the effect of WISC total IQ. The studies listed are as follows: Said et al (18), Cetingül et al (19), Raymond-Speden et al (20), Anderson et al (21), Reinfjell et al (22), Lofstad et al (23), Carey et al (24), Aukema et al (25), Halsey et al (26), Zou et al (27), Kesler et al (28), Reddick et al (29), Kim et al (30), Van Der Plas et al (31), Darling et al (32) and Sherief et al (33). SMD, standardized mean difference; WISC, Wechsler Intelligence Scale for Children; IQ, intelligence quotient.

Figure 3.

Forest plot presenting the meta-analysis based on SMDs for the effect of WISC verbal IQ. The studies listed are as follows: Said et al (18), Cetingül et al (19), Raymond-Speden et al (20), Anderson et al (21), Reinfjell et al (22), Lofstad et al (23), Aukema et al (25), Halsey et al (26), Kim et al (30) and Sherief et al (33). SMD, standardized mean difference; WISC, Wechsler Intelligence Scale for Children; IQ, intelligence quotient.

Figure 4.

Forest plot presenting the meta-analysis based on SMDs for the effect of WISC performance IQ. The studies listed are as follows: Said et al (18), Cetingül et al (19), Raymond-Speden et al (20), Anderson et al (21), Reinfjell et al (22), Lofstad et al (23), Halsey et al (26), Kim et al (30) and Sherief et al (33). SMD, standardized mean difference; WISC, Wechsler Intelligence Scale for Children; IQ, intelligence quotient.