Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review |
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| Affiliation: | 1. Children''s Center for Cancer and Blood Diseases, Children''s Hospital Los Angeles, Los Angeles, California;2. Dana-Farber/Boston Children''s Cancer and Blood Disorders Center, Boston, Massachusetts;3. Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland;4. Willem-Alexander Children''s Hospital, SCT Unit, Leiden University Medical Center, Leiden, The Netherlands;5. University of California San Francisco, Department of Pediatrics, Allergy, Immunology, and Blood and Marrow Transplant Division, San Francisco, California;6. Division of Immunology, Boston Children''s Hospital, Harvard Medical School, Boston, Massachusetts;7. Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland;8. St. Louis Children''s Hospital, Washington University, St. Louis, Missouri;9. Great North Children''s Hospital and Northern Institute of Cancer Research, Newcastle upon Tyne, United Kingdom;10. UCSF Benioff Children''s Hospital Oakland, Oakland, California;11. Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota;12. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington |
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| Abstract: | The intensified administration of chemotherapeutic drugs has gradually replaced cranial radiation therapy (CRT) for the treatment of childhood acute lymphoblastic leukemia (ALL). While CRT is often implicated in neurocognitive impairment in ALL survivors, there is a paucity of the literature that evaluates the persistence of neurocognitive deficits in long-term survivors of pediatric ALL who were treated with contemporary chemotherapy-only protocols. Results from this systematic review concurred to the probable cognitive-sparing effect of chemotherapy-based protocols over CRT in long-term survivors. However, coupled with multiple intrinsic and extrinsic factors, survivors who received chemotherapy treatment still suffered from apparent cognitive impairment, particularly in the attention and executive function domains. Notably, there is evidence to suggest that the late neurotoxic effect of methotrexate on survivors’ neurocognitive performance may be dose-related. This review also recommends future pharmacokinetic, neuroimaging and genetic studies to illuminate the multifactorial nature of this subject matter and discusses the potential value of neurochemical, physiological, inflammatory and genetic markers for the prediction of susceptibility to neurocognitive impairment in long-term survivors of childhood ALL. |
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| Keywords: | Acute lymphoblastic leukemia Cancer survivorship Chemotherapy Neurocognitive Pediatric cancer |
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