Prospective Evaluation of Acute Graft-Versus-Host Disease

Abstract

Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation. Severe GVHD carries significant morbidity and mortality and remains one of the leading causes of treatment failure. Unfortunately, intestinal GVHD may present with a variety of non-specific symptoms and diagnosis based on clinical presentation is often inaccurate; biopsy is therefore needed for definitive diagnosis. At present, the optimal endoscopic approach to the diagnosis of gastrointestinal GVHD remains uncertain. The primary aims of our study were: (1) to evaluate the yield of upper versus lower endoscopy, and (2) to determine which anatomic regions were most likely to provide a histologic diagnosis. We conducted a prospective study of 27 consecutive patients who had undergone stem cell transplantation within the past 100 days and were referred to the Yale Gastrointestinal Procedure center between August 2002 and February 2006 for the evaluation of suspected acute GVHD. All patients underwent standardized endoscopic evaluation of the upper and lower gastrointestinal tract with biopsies. The diagnostic yield of upper versus lower endoscopy was compared in all patients. GVHD was identified in 18 of the 27 patients (67%). Of those with GVHD, 15 patients (83%) had diffuse intestinal involvement. Six of 10 patients (60%) with an endoscopically normal EGD had GVHD on biopsies of the upper gastrointestinal tract. Six of 13 (46%) patients with an endoscopically normal appearing colonoscopy had GVHD on colonic biopsies. Two of 18 (11%) patients had isolated GVHD of the upper intestinal tract and 1 (6%) had isolated colonic GVHD. Rectal biopsy alone identified 89% (16 of 18) of GVHD cases and all 16 cases of GVHD with colonic involvement. A diagnosis of GVHD was not altered by the additional performance of biopsy of the proximal colon or terminal ileum. In the present study, the majority of cases of acute GVHD demonstrate diffuse upper and lower gastrointestinal involvement with rectal, sigmoid, gastric and duodenal biopsies having similarly diagnostic yield. Based on our findings, we recommend starting with flexible sigmoidoscopy with rectal biopsy alone in patients who are poor candidates to undergo full colonoscopy with sedation or in those in whom GVHD is strongly suspected based on clinical findings. However, more extensive evaluations may be necessary to rule out infection and should be considered in those with no contraindications to sedation and in whom other differential diagnoses are also being considered.