Abdominal CT in the Clinical Evaluation of Acute Graft-Versus-Host Disease of the Gastrointestinal Tract: Diffuse Small Intestine Involvement Is Associated with Severity and Outcome.
Authors: Shimoni Avichai , Hertz Marjory , Yeshurun Moshe , Portnoy Orit , Hardan Izhar , Amitai Michal , Nagler Arnon , Apter Sara 
Published: October 2019

Abstract
Acute graft-versus-host disease (GVHD) is the major treatment-related complication after allogeneic stem-cell transplantation. Acute GVHD of the gastrointestinal (GI) tract is a clinical diagnosis supported by histo-pathological findings. The presenting symptom is most often large volume diarrhea.The volume of diarrhea determines disease stage and prognosis, however its assessment is inconvenient and inaccurate due to low compliance. Moreover, patients (pts) may present with atypical symptoms such as abdominal pain and vomiting. Also, biopsies of the GI-tract may be falsely negative due to patchy involvement or may be contraindicated in pts with severe thrombocytopenia. This study was designed to determine the CT features associated with acute GI GVHD and to evaluate its role in the assessment of severity and prognosis. Thirty-four consecutive pts with symptoms suggestive of acute GI GVHD were evaluated early after presentation by abdominal CT. The median age was 52 years (range, 20–66). Diagnoses included AML (n=10), ALL (n=5), multiple myeloma (n=8), NHL (n=5), CLL (n=4) and others (n=2). The donors were HLA-matches sibling (n=21), 1-Ag mismatched relative (n=2) or matched unrelated (n=11). Nine pts had myeloablative conditioning and 25 had reduced-intensity regimens. None had infectious etiology by standard evaluation. Eighteen pts had clinical stage I–II of GI-GVHD and 14 had clinical stage III–IV by the Glucksberg criteria. Thirty-two pts had pathological finding in CT. The most consistent finding was thickening of the bowel wall, which was limited to the small (n=11) or large bowel (n=5) or involved both (n=16). Involvement was diffuse or segmental. Other manifestations included intestinal dilatation (n=11), mucosal enhancement (n=3) and gastric wall thickening (n=7). Extra-intestinal findings were also common and included mesenteric stranding (n=22), ascites (n=13) and biliary systems abnormalities (n=11). Ten pts had urinary excretion of orally administered gastrografin which is not normally absorbed by an intact intestine. Diffuse thickening of the small bowel wall and/or any involvement of the large intestine were patterns associated with severe clinical presentation. Eleven and 14 of the 16 patients with clinical stage III–IV GI-GVHD had these patterns, respectively, compared to 5 and 7 of the 18 pts with stage I–II disease (p=0.03). Overall, nineteen pts responded to immunesuppressive therapy. Nine pts are alive; 25 died, 13 of complications directly related to GVHD. Diffuse small bowel disease was associated with poor prognosis. Only six of 16 pts showing this pattern responded to immunosuppressive therapy compared to thirteen of 18 pts without this pattern (p=0.05). The cumulative incidence of GVHD-related death was and 56% (95% CI, 37–87) and 25% (95% CI 11–58), respectively (p=0.05), however overall survival was not significantly different in the two groups. In conclusion, abdominal CT may have an important role in the diagnosis of GVHD in atypical presentations and in the prognostic evaluation. Diffuse small intestinal disease and any colon disease are associated with severe clinical disease. Diffuse small intestinal disease is also associated with poor response to therapy and GVHD-related mortality. CT findings may direct the clinician in determining the therapeutic approach.