Background: the Primary medication used in acute lymphoblastic leukemia is

methotrexate, and the problem with this treatment is that it is hazardous to cancer

patients. The study aim was evaluation of vitamin D effect on methotrexate toxicity,

including oral ulcerations, bone marrow, renal, and hepatic toxicity, besides

inflammatory mediators; IL-6 and TNF-α role in this toxicity. Methods: Methotrexate

was used to treat 58 patients with acute lymphoblastic leukemia in a clinical trial which

was a double-blinded randomized study; (30 in Group A - no vitamin D for 2 weeks

after methotrexate treatment) and (28 in Group B - patient received vitamin D3 drops

for 2 weeks after methotrexate treatment). Results: Leukocytic count, Hemoglobin and

platelet count were significantly lower in patients didn't receive Vitamin D compared

to patients received Vitamin D. Serum bilirubin, liver enzymes, urea, creatinine, IL-6

and TNF-α levels were significantly higher in patients didn't receive vitamin D

compared to the other group, while there is no significant change in levels of albumin

and total proteins in both groups. 24 hours after 2nd cycle of methotrexate, the study

group's methotrexate level significantly decreased, while it significantly elevated in the

control group. Mild oral mucositis grade (I, II) showed a significant increase in the

study group and a decrease in the control group, whereas severe oral mucositis grade

(III, IV) showed a significant decrease in the study group and an increase in the control

one. Conclusion: Medication with vitamin D may be a significant factor in reducing

methotrexate toxicity.