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Small bowel enterocyte abnormalities caused by methotrexate treatment in acute lymphoblastic leukaemia of childhood
Insights
Methotrexate treatment in children with acute lymphoblastic leukaemia causes significant damage to intestinal cells, leading to malabsorption. These findings highlight the direct toxic effects of this chemotherapy on the small intestine.
Area of Science:
- Gastroenterology
- Pediatric Oncology
- Cell Biology
Background:
- Methotrexate is a common chemotherapy agent used in treating acute lymphoblastic leukaemia (ALL).
- Patients undergoing chemotherapy may experience gastrointestinal side effects, including malabsorption.
- The specific impact of methotrexate on the small intestinal lining in children with ALL is not fully understood.
Purpose of the Study:
- To investigate the morphological changes in the jejunum of children with ALL undergoing methotrexate treatment.
- To compare these changes with those in children without leukaemia or on different treatments.
- To elucidate the potential mechanisms behind methotrexate-induced enterocyte damage and malabsorption.
Main Methods:
- Jejunal biopsy specimens were obtained from 10 children with ALL on methotrexate and 10 controls.
- Light and electron microscopy were used to examine enterocyte morphology.
- Specimens were analyzed based on the timing of methotrexate administration relative to biopsy.
Main Results:
- Children on methotrexate showed marked morphological abnormalities in villus enterocytes.
- Abnormalities included distended intercellular spaces, cell vacuolation, and patchy necrosis.
- Changes were most severe when methotrexate was administered 24-72 hours before biopsy.
Conclusions:
- Methotrexate treatment causes direct toxic effects on mature enterocytes.
- It also interferes with the generation of new crypt cells, potentially leading to enterocyte aging and loss.
- These pathological changes likely contribute to malabsorption observed in children with ALL on methotrexate therapy.
Abstract:
Jejunal biopsy specimens from 10 children with acute lymphoblastic leukaemia on methotrexate treatment were compared with 10 from children being investigated for diarrhoea or failure to thrive. In association with methotrexate treatment on both light and electron microscopy, there were marked morphological abnormalities in the villus enterocytes. These consisted of a striking distention of the lateral basal intercellular spaces, cell vacuolation and patchy necrosis and was most marked when methotrexate treatment was given between 24 and 72 h before biopsy. Two mechanisms may be involved: an early direct toxic effect on the mature enterocyte coupled with interference with crypt cell generation, possibly causing ageing and loss of cells proximal to the normal extrusion zone. These pathological changes may account for the malabsorption in association with methotrexate treatment.