Cognitive functioning of children treated for acute lymphoblastic leukaemia with chemotherapy-only

Acute lymphoblastic leukaemia (ALL) is the most common form of malignancy in children. With current survival rates of approximately 85%, increasing attention is paid to the potentially adverse effects of treatment on quality of life in children with ALL. Until the mid-eighties, prophylactic central nervous system irradiation was an essential element of leukaemia treatment but this irradiation has been associated with deleterious effects on cognitive abilities. With the introduction of 'chemotherapy-only', protocols which replaced irradiation by intrathecal and high dose systemic chemotherapy, the number of patients with cognitive deterioration has dramatically decreased with stable or even improved survival rates. However, despite a more favourable neuropsychological outcome after chemotherapy-only protocols compared to protocols including central nervous irradiation, there is no consensus concerning possible more subtle negative effects of chemotherapy on intellectual development and specific neuropsychologcial functions such as attention, memory, and visual motor abilities. Prior studies concerning neuropsycological outcome after chemotherapy-only in children with ALL had major methodological limitations. In 1999, the nationwide study presented in this thesis was therefore initiated by the Paediatric Oncology Centre of the University Medical Centre Groningen. Main objective was to assess potential early and late negative late effects of chemotherapy-only on cognitive functioning in children with ALL. In this prospective longitudinal study, 50 newly diagnosed consecutive ALL patients aged 4 to 12 years treated according to Dutch Childhood Oncology Group (DCOG) ALL-9 protocol were included. Neuropsychological functioning of patients (median age at baseline testing 8.2 years) was assessed by an extensive test battery shortly after diagnosis, a few months after cessation of therapy and two years later. Repeated evaluations included measures of intelligence, memory, attention, visual-constructive function and fine-motor abilities. We applied hierarchical regression analyses and multilevel analyses to assess possible changes and differences over time compared to siblings. Multilevel technique allowed for the inclusion of patients with missing data in the analyses. Patients' results were additionally compared to population norms to assess whether test performance was in the normal range.