17 September 2018

Children who received chemotherapy for acute lymphoblastic (ALL) leukaemia may be more likely to experience specific types of delayed neurodevelopment, new findings show.

To examine the long-term cognitive effects of treatment for leukaemia, brain imaging techniques were used to study the connections between different parts of the brain, and how they may be disrupted as a result of chemotherapy.

Dr Kevin Krull and colleagues at St. Jude Children's Research Hospital, Memphis, Tennessee, USA, examined 161 long-term survivors of acute lymphoblastic leukaemia aged 8 to 21 years.

Problems with executive functions are frequent amongst survivors of ALL, and can be wide ranging, such as difficulties with concentration, impulse control, adapting to different situations, and planning. To try to understand what causes these problems, the researchers looked at survivors with and without executive dysfunction, looking for differences in the connectivity within the brain and how the brain processes information.

Among the participants with executive dysfunction, they found their brains had impaired global connectivity – a measure of the brain’s ability for process different pieces of information at the same time.

The authors report that the risk for impaired connectivity and poorer information processing is higher for those survivors who were diagnosed at a younger age, who received more chemotherapy containing methotrexate, and in particular those who received multiple intrathecal methotrexate injections.

The results of the study were published in the journal Brain Connectivity. The journal’s editor, Dr Christopher Pawela, said: "The ten-year cure rate for acute lymphoblastic leukaemia is approaching over 90% in children. Long-term cognitive impairment is a serious issue facing survivors and there has been a lack of understanding of the mechanism of how acute lymphoblastic leukaemia and chemotherapy affect brain function."

He said the study "establishes for the first time using brain imaging that age of diagnosis and the length of chemotherapeutic treatment have compounding maladaptive effects on the brain networks involved in executive cognitive function."

The authors of the study conclude that the results “highlight the need for interventional strategies that will help prevent and manage cognitive impairment […] in patients with pediatric ALL and assist these patients with maintaining brain health across the life span.”

Source: Kesler, S.R., Ogg, R., Reddick, W.E., Phillips, N., Scoggins, M., Glass, J.O., Cheung, Y.T., Pui, C.H., Robison, L.L., Hudson, M.M., Krull, K.R. (2018), “Brain Network Connectivity and Executive Function in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia”, Brain Connectivity, available at doi: 10.1089/brain.2017.0574.


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