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van der Plas E, Nieman BJ, Butcher DT, et al. Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate. J Can Acad Child Adolesc Psychiatry. 2015;24(1):25-32
van der Plas, E., Nieman, B. J., Butcher, D. T., Hitzler, J. K., Weksberg, R., Ito, S., & Schachar, R. (2015). Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate. Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent, 24(1), 25-32.
van der Plas, Ellen, et al. "Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate." Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent vol. 24,1 (2015): 25-32.
van der Plas E, Nieman BJ, Butcher DT, Hitzler JK, Weksberg R, Ito S, Schachar R. Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate. J Can Acad Child Adolesc Psychiatry. 2015;24(1):25-32. Epub 2015 Mar 04. PMID: 26336377; PMCID: PMC4357331.
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J Can Acad Child Adolesc Psychiatry. 2015;24(1):25-32. Epub 2015 Mar 04.

Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate.

Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent

Ellen van der Plas, Brian J Nieman, Darci T Butcher, Johann K Hitzler, Rosanna Weksberg, Shinya Ito, Russell Schachar

Affiliations

  1. Psychiatry Department, The Hospital for Sick Children, Toronto, Ontario ; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario.
  2. Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario ; Department of Medical Biophysics, University of Toronto, Toronto, Ontario.
  3. Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario.
  4. Division of Haematology/Oncology and Cancer and Blood, Department of Pediatrics, the Hospital for Sick Children, Toronto, Ontario.
  5. Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario ; Division of Clinical and Metabolic Genetics, Department of Paediatrics, the Hospital for Sick Children, Toronto, Ontario ; Institute of Medical Science, The University of Toronto, Toronto, Ontario.
  6. Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, the Hospital for Sick Children, Toronto, Ontario.

PMID: 26336377 PMCID: PMC4357331

Abstract

Childhood cancer survivors frequently experience long-lasting consequences of chemotherapy on health outcomes. Neurocognitive late effects of chemotherapy occur in 40 - 60% of acute lymphoblastic leukemia (ALL) survivors. These deficits affect mental health, school performance, job success, and are associated with poor quality of life, therefore presenting a clinical challenge for psychiatrists. However, not all cancer survivors are impacted by treatment in the same manner and emerging evidence suggests that genetic variation may modulate neurocognitive outcomes. Much like other complex psychopathologies, neurocognitive deficits in cancer survivors are the result of complex interactions between genetic and environmental variables. This review describes adverse neurocognitive outcomes observed in survivors of acute lymphoblastic leukemia (ALL) and discusses genetic variability in biochemical pathways targeted by chemotherapeutic agents as a possible mechanism contributing to psychopathology in ALL survivors.

Keywords: acute lymphoblastic leukemia; chemotherapy; genetic variants; neurocognitive late effects; one-carbon metabolism

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