Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate.
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.
Psychiatry Department, The Hospital for Sick Children, Toronto, Ontario ; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario.
Ellen
E
van der Plas
Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario ; Department of Medical Biophysics, University of Toronto, Toronto, Ontario.
Brian J
BJ
Nieman
Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario.
Darci T
DT
Butcher
Division of Haematology/Oncology and Cancer and Blood, Department of Pediatrics, the Hospital for Sick Children, Toronto, Ontario.
Johann K
JK
Hitzler
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.
Rosanna
R
Weksberg
Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, the Hospital for Sick Children, Toronto, Ontario.
Shinya
S
Ito
Psychiatry Department, The Hospital for Sick Children, Toronto, Ontario ; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario.
Russell
R
Schachar
acute lymphoblastic leukemia; chemotherapy; genetic variants; neurocognitive late effects; one-carbon metabolism