Gastro-intestinal toxicity related to bone marrow transplantation: Disruption of the intestinal barrier precedes clinical findings

The intensive cytotoxic treatment given in connection with bone marrow transplantations induces severe injury to the gut consistent with an increase in intestinal permeability. Currently, extent of the gut injury is assessed by inspecting the mouth and recording symptoms deriving from the gastro-intestinal tract. The aims of this study were to evaluate whether changes in permeability correlate with clinical assessment of gut toxicity, according to the WHO criteria, and also to examine the duration of intestinal permeability after high-dose chemotherapy. In 18 consecutive patients undergoing bone marrow transplantation, gastrointestinal permeability was assessed by a Cr-51-EDTA absorption test before the start of cytotoxic treatment, and 4, 7, 10 and 14 days after stem-cell infusion. In another seven patients, permeability was assessed 2 days after the start of cytotoxic treatment, and 1, 7 and 14 days after stem cell infusion. During the same period, oral- and non-oral clinical toxicity according to the WHO criteria were recorded. Permeability increased significantly 2 days after the start of cytotoxic treatment (P < 0.05), on day 1 (P < 0.05), on day 4 (P < 0.0005), on day 7 (P < 0.0005) and on day 10 (P < 0.005) after stem cell infusion, compared with pre-treatment permeability. Despite significant barrier dysfunction, clinical toxicity was very moderate in the early transplantation course. Gastro-intestinal, but not oral clinical toxicity requiring therapy, was consistent with a significant increase in permeability compared with no clinical toxicity or toxicity not requiring therapy. Similarly, cumulative gastro-intestinal, but not oral toxicity correlated positively with the increase in permeability. The permeability test was unable to predict the severity of the clinical gastro-intestinal toxicity.