Methotrexate Induced Encephalopathy in Acute Lymphoblastic Leukemia in Omani Children

Abstract

Objectives: To investigate the incidence and clinical profile of methotrexate related encephalopathy in Omani children with pre-B Acute Lymphoblastic Leukemia (ALL). Methods:A retrospective cohort study of 8 children with Pre B Acute Lymphoblastic Leukemia who developed encephalopathy while being treated according to United Kingdome Research Council (UK MRC) ALL protocol during the period between [2005][2006][2007][2008][2009][2010][2011][2012][2013][2014][2015][2016]. Demographic data, clinical presentation, diagnosis and treatment are discussed.Results: Eight children (4 males,4 females), 7 of them were above 10 years of age, with ALL treated according to intermediate risk UK MRC ALL protocol developed transient encephalopathy during treatment. Six children had one episode, one had two episodes, and last one had 3 episodes. All except one recovered completely within 24-96 hours after symptomatic treatment. This one had extensive neurological involvement and took seven days to recover. All children had normal coagulation and thrombophilia studies. Four out of the 8 patients subsequently received intrathecal (IT) cytarabine instead of methotrexate without any neurotoxicity. The other 4 patients received further IT methotrexate. Three of these four had recurrence on re-challenge, while the fourth remained asymptomatic. Seven children with neurotoxicity had MRI findings of white matter changes. Six out of eight children are in complete remission while two died later following relapse. Conclusion:Methotrexate induced encephalopathy can occur after intrathecal methotrexate treatment especially in children older than 10 years of age. Diffusion weighted MRI is the currently available best diagnostic tool. Treatment of methotrexate neurotoxicity is mainly supportive and recovery is usually complete. Further studies are needed to understand the mechanism of neurotoxicity, risk factors, and to define the safe dose to prevent such neurotoxicity.