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Pediatr Blood Cancer. 2016 Jan;63(1):133-8. doi: 10.1002/pbc.25690. Epub 2015 Aug 27.

Neurocognitive Outcome in Very Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia After Treatment with Chemotherapy Only.

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Department of Paediatric Medicine, Women and Children's Division, Oslo University Hospital, Rikshospitalet, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Psychosomatic Medicine, Oslo University Hospital, Oslo, Norway.
Department of Psychology, University of Oslo, Oslo, Norway.
Department of Physical Medicine and Rehabilitation, Unit of Neuropsychology, Oslo University Hospital, Oslo, Norway.
Norwegian Centre for Mental Disorder Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
National Resource Centre for Late Effects After Cancer Treatment, Department of Oncology, Oslo University Hospital, Radiumhospitalet, Norway.



There is a concern regarding long-term cognitive late effects after treatment for acute lymphoblastic leukemia (ALL). The present study assessed neuropsychological function in very long-term childhood ALL survivors treated with chemotherapy only. We also investigated associations between neurocognitive performance and individual treatment load.


One-hundred and twelve adult ALL survivors, diagnosed 1970-2002 before age 16 and treated with chemotherapy only, and 100 comparison peers underwent neuropsychological tests covering processing speed, executive functions, working memory, and verbal learning and memory. Individual cumulative doses of cytostatic agents were extracted from the medical records for each patient.


Mean age at diagnosis for survivors was 6.3 years and mean follow-up time was 22.6 years. There was no difference in general intellectual ability between survivors and comparison peers. However, survivors performed significantly more poorly in the neurocognitive domains' processing speed (P = 0.003, Cohen's d 0.48), executive functions, and working memory (both P < 0.001, Cohen's d 0.81-0.95). Among survivors, the rates of poor neurocognitive performance (>1.5 SD below control mean) for processing speed was 22%, executive functions 31%, working memory 34%, and verbal learning and memory 16%. Comparing survivors with poor versus normal neurocognitive performance, we found no difference with respect to cumulative doses of any of the cytostatic agents, age at diagnosis, or gender.


Very long-term survivors of childhood ALL treated exclusively with chemotherapy showed no impairment in general intellectual ability, but significantly poorer performance in several neurocognitive domains than comparison peers. However, no associations emerged between neurocognitive impairment and treatment burden.


CNS-directed chemotherapy; acute lymphoblastic leukemia; childhood cancer survivor; cognitive function; late effects

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