Leukoencephalopathy As Marker of Cognitive Impairment After Chemotherapy For Childhood ALL

MedicalResearch.com Interview with:
Yin Ting Cheung, PhD

Department of Epidemiology and Cancer Control and
Noah D Sabin, MD
Department of Diagnostic Imaging
St Jude Children’s Research Hospital
Memphis, TN

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Long-term survivors of childhood acute lymphoblastic leukemia (ALL) who are treated with high-dose intravenous methotrexate or intrathecal chemotherapy are at risk for neurocognitive impairment, particularly in cognitive processes such as processing speed, attention and executive function. However, many children who receive these therapies do not experience significant impairments, suggesting the need for biomarkers to identify patients at greatest risk. Prior research from our team demonstrated that, during chemotherapy, patients were at risk for white matter changes in the brain, also known as leukoencephalopathy. No studies documented the persistence or impact of brain leukoencephalopathy in long-term survivors of childhood ALL treated on contemporary chemotherapy-only protocols.

In this study, we included prospective neuroimaging from active therapy to long-term follow-up, and comprehensive assessment of brain structural and functional outcomes in long-term survivors of ALL treated with contemporary risk-adapted chemotherapy. We demonstrated that survivors who developed leukoencephalopathy during therapy displayed more neurobehavioral problems at more than 5 years post-diagnosis. Moreover, these survivors also had reduced white matter integrity at long-term follow-up, and these structural abnormalities were concurrently associated with the neurobehavioral problems.

MedicalResearch.com: What should readers take away from your report?

Response: Long-term survivors of childhood ALL treated with contemporary chemotherapy-only protocols are at risk for neurobehavioral problems; those who develop leukoencephalopathy during chemotherapy are at highest risk. Leukoencephalopathy during chemotherapy is also predictive of white matter microstructural abnormalities in the brain during long-term survivorship. Close monitoring of neurobehavioral development in this population is warranted.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Future research should determine whether early preventative cognitive and/or educational interventions in survivors who develop leukencephalopathy reduce the risk for long-term neurobehavioral problems and brain white matter abnormalities.

Future research should also include identifying biomarkers related to white matter damage within cerebrospinal fluid collected in survivors during active treatment to better understand the specific neurophysiologic process of brain injury.

MedicalResearch.com: Is there anything else you would like to add?

Response: Most survivors of childhood ALL will not develop neurobehavioral problems, though for the significant subset of patients who do, the problems can have a significant impact on educational attainment, future employment and level of adult independence. Thus, early repated screening and early intervention is essential.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.


Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis
Cheung, Yin Ting et al.
The Lancet Haematology , Volume 3 , Issue 10 , e456 – e466

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Last Updated on October 4, 2016 by Marie Benz MD FAAD