Jejunal crypt cell abnormalities associated with methotrexate treatment in children with acute lymphoblastic leukaemia.

Jejunal mucosal crypts were examined in jejunal biopsies from eight children with acute lymphoblastic leukaemia who had recently received methotrexate treatment. By comparison with biopsies from children under investigation for suspected malabsorption crypt mitosis was significantly reduced and showed a negative correlation with the dose of methotrexate given prior to biopsy. The three major cell types were studied under light and transmission electron microscopy. Gut endocrine cells were unaffected by therapy and immature crypt enterocytes showed only patchy degenerative abnormalities. By contrast a number of Paneth cells showed striking structural alterations with vacuolar dilatation of the cytoplasm. The extent of this correlated with the time since methotrexate treatment rather than its dose and may have been a functional response rather than of a toxic nature.