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A Systematic Review of Neuropsychological Studies Confirms that Adequate Folinic Acid Rescue Prevents Post Methotrexate Neurotoxicity
  • Michelle Sadeh,
  • Helen Toledano,
  • Ian Cohen
Michelle Sadeh
Israel Cancer Association
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Helen Toledano
Schneider Children's Medical Center of Israel
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Ian Cohen
Schneider Children's Medical Center of Israel Department of Internal Pediatrics A
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Abstract

A comprehensive literature search was performed of all databases of the Web of Science Citation Index, during 1990-2020, for the terms: neuropsychological, neurocognitive, cognitive, acute lymphoblastic (and lymphocytic) leukemia, and osteogenic sarcoma, to see if there was evidence of a correlation between folinic acid (FA) rescue inadequacy and long-term cognitive damage. All English language, peer-reviewed articles of neuropsychological assessments of children who had been treated with high-dose methotrexate without irradiation, and which included details of methotrexate and FA schedules, were selected. Four groups of studies were found and analyzed, Those with no evidence of cognitive deterioration, Those with evidence of cognitive deterioration, studies with more than one protocol grouped together, preventing separate analysis of any protocols, and those with significant serious methodical problems. In all studies, protocols without evidence of cognitive deterioration reported adequate FA rescue, and those with evidence of cognitive deterioration reported inadequate FA rescue.