Diffuse intestinal ulceration after marrow transplantation: a clinicopathologic study of 13 patients

The cases of 13 allogeneic marrow transplant recipients who had undergone laparotomy for manifestations of severe enteritis were reviewed to determine the causes of the severe intestinal disease and to assess the relation between clinical, histologic, and microbiologic findings. Laparotomies were performed a median of 63 days (range, 11 to 273 days) after transplantation for suspected peritonitis, intestinal obstruction, or bleeding. Intestinal tissue was available from small bowel resections in nine patients, intraoperative biopsies in one, and from autopsies in three patients who died shortly after laparotomy. Widespread small bowel ulceration was present in all 13 cases. Four causes of ulceration were identified: chemoradiation toxicity (n = 2), acute graft-versus-host disease (GVHD) (n = 5), opportunistic infections superimposed on either GVHD or toxicity from chemotherapy (n = 4), and Epstein-Barr virus-associated lymphoproliferative disorder (n = 2). Intestinal infections, unrecognized before laparotomy, were due to cytomegalovirus (CMV), herpes simplex virus (HSV), adenovirus, and Torulopsis glabrata. CMV- and HSV-infected cells, often lacking diagnostic inclusions, were identified in the intestine by in situ hybridization with biotinylated DNA probes. Eleven patients died in the perioperative period, and two died 452 and 558 days after surgery of complications of chronic GVHD. Poor outcomes were related to extensive intestinal involvement, which was commonly underestimated before surgery, failure to diagnose intestinal infections early, poor marrow function, impaired immunity, and refractoriness of severe GVHD.