No evidence for longterm chemotherapy-induced neurotoxicity for pediatric ALL patients:A prospective study

Survival rates of pediatric Acute Lymphoblastic Leukemia (ALL) patients have been increasing during the last decades. Given that radiotherapy for central nervous prophylaxis is not used in our frontline therapy anymore, and treatment became only chemotherapy based, chemotherapy-induced side effects, such as cognitive decline, become important to assess. Although chemotherapy-induced neurotoxicity was demonstrated in cross-sectional studies, the number of follow-up studies remains limited. Still, to investigate long-term neurotoxic effects, a longitudinal design is most suitable.

Methode

We evaluated neurocognitive development of 94 Flemish pediatric ALL patients, standard risk, diagnosed between 1990 and 1997, who were treated according to the EORTC 58881. Intellectual functioning was assessed with the WISC-R every three years since diagnosis, according to their age. In a fixed effects repeated measures analysis: gender, disease risk, education of the parents, age at diagnosis, IQ subscale (verbal (VIQ) vs performal (PIQ) intelligence), and test moment were included as predictors for IQ.

Resultaten

IQ scores did not decline over time. Although PIQ scores were significantly lower than VIQ at baseline, PIQ scores increased such that this difference disappeared throughout time. A significant interaction effect of IQ subscale and test moment (p=.0079) was found. IQ scores were not predicted by gender (p=.78), nor by disease risk (p=.49), but were significantly higher when one parent had followed higher education (p<.0001). Finally, diagnosis at lower age (p=.0009) predicted lower IQ scores.

Conclusie

Given that IQ scores did not decline, nor did disease risk relate to cognition, our findings suggest the absence of long-term chemotherapy-induced neurotoxicity. Lower IQ scores for patients who were diagnosed at younger age however, highlight the stronger impact of the disease and/or treatment at younger age. Given that PIQ was most explicitly lowered at baseline, specifically for patients diagnosed at younger age, this may suggest that performal functioning is more vulnerable to acute neurotoxicity.

Auteurs

Sleurs, C. MSc^{1, 2}, Lemiere, J. PhD¹, Vercruysse, T. MSc¹, Nolf, N. MSc3, Van Calster B. PhD², Deprez S. PhD⁴, Renard M. MD¹,Vandecruys E. MD³, Benoit Y. MD, PhD³, Uyttebroeck A. MD, PhD^{1, 2}

1 Department of Pediatric Haematology and Oncology, University Hospitals Leuven, Belgium

2 Department of Development and Regeneration, KU Leuven, Belgium

3 Departement of Pediatric Haematology and Oncology, Ghent University Hospital, Belgium

4 Department of Radiology, KU Leuven, Belgium