Halal Research Center of Islamic Republic of Iran. Tel.: +98-21-88909033 Fax: +98-21-88890858 Email: jhhhm@halal.ac.ir IR.MCIG No. 85915 Human, Health and Halal Metrics 2717-1027 2 1 2021 10 05 Methotrexate-induced neurocognitive late effects in treatment of pediatric acute lymphoblastic leukemia: a review 63 74 138886 10.30502/jhhhm.2021.283539.1031 EN Mahdi Taherian General Directorate of Natural, Traditional and Complementary Products, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran. 0000-0003-4568-2837 Zohreh Tajabadi School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Arash Azhideh School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Reza Taherian School of Medicine, Hamadan University of Medical Sciences, Hamdan, Iran. 0000-0002-5556-6904 Journal Article 2021 04 29 <strong>Background and objective</strong>: Childhood cancer survivors frequently experience long-lasting consequences of chemotherapy. Acute lymphoblastic leukemia is one of the most common malignancies that occur during childhood. By the help of new protocols, 5-year survival is about 80%. Despite all improvement in treatment and increasing surveillance, morbidities of these treatments are lifetime. The aim of this study was to review the recent updates on chronic neurologic deficits occurred by treatment of acute lymphoblastic leukemia, risk factors of these neurologic deficits, and prevention of their side-effects. Also, this review discusses the genetic variability in biochemical pathways targeted by chemotherapeutic agents as a possible mechanism contributed to psychopathology in acute lymphoblastic leukemia survivors. <strong>Results and conclusion</strong>: The most important drug used for treatment of acute lymphoblastic leukemia is methotrexate. It is also the main drug for central nervous system prophylaxis. Most of chemotherapies drugs cannot pass blood brain barrier but methotrexate is an exception. Methotrexate is a double-edge sword, because it can pass blood brain barrier and can be used for central nervous system prophylaxis to decrease the relapses. On the other hand, it can cause chronic neurologic deficits as a result of its passage from blood brain barrier in the developing brain. In conclusion, prophylactic interventions during treatment (e.g., administration of leucovorin) and after treatment (e.g., cognitive training and maintenance of academic growth) are effective routes in prevention of late effects in survivors of acute lymphoblastic leukemia. https://jhhhm.halal.ac.ir/article_138886_eadfc497d51889591ed1ba1e1995604b.pdf