Methotrexate-induced neurocognitive late effects in treatment of pediatric acute lymphoblastic leukemia: a review

Document Type : Review


1 General Directorate of Natural, Traditional and Complementary Products, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran.

2 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 School of Medicine, Hamadan University of Medical Sciences, Hamdan, Iran.


Background and objective: 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.
Results and conclusion: 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.


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