BACKGROUND MTX induced neurotoxicity is often associated with LE, and diagnosed by white matter hyperintensities in MRI. This study was done to study: 1) risk and prevalence of LE in ALL receiving MTX through sequential MRI brain. 2) Safety of re-administration of MTX in toxic LE. 3) Relationship of serum homocysteine, B12 and folate with MTX induced LE. METHODOLOGY 34 pediatric ALL/lymphoblastic Lymphoma patients of age ≤18 years between June 2019 and 2020 were enrolled. Induction chemotherapy was initiated as per modified ALL IC BFM 2002 protocol. All patients underwent MRI brain and serum homocysteine, B12, folate level sequentially as per protocol at 4 occasions. 1st – at diagnosis; 2nd – post consolidation; 3rd – post extra compartment therapy; 4th – in maintenance. RESULTS LE secondary to MTX occurred in 7of116(6.03%) on MRI brain in 5of33(15.15%) patients of which 1(3.03%) had symptomatic LE and 4(12.12%) were asymptomatic. There was no difference in incidence with respect to mode of MTX administration. There was no increase in incidence after 4 courses of HD-MTX. MRI at baseline was not a predictor of development of LE. 3of5 LE patients had abnormal B12/folate/homocysteine with corresponding abnormal MRI brain. Low folate and/or b12 levels also led to increased systemic toxicity in few patients post methotrexate therapy. t(1:19) and t(9:22) were associated with leukoencephalopathy but t(12:21) was not associated with LE. CONCLUSION Most patients of MTX induced LE can be rechallenged with MTX. MRI at baseline is not a predictor of development of LE.