Abstract
Acute gastro-intestinal graft-versus-host disease (GI-GVHD) is a major complication following allogeneic stem cell transplantation (allo-SCT) and results in high morbidity and mortality. Diagnosis of GI-GVHD is problematic due a lack of specific symptoms and confounding variables in allo-SCT patients. Although diarrhea is the most common (but non-specific) presenting symptom in acute GI-GVHD, diagnosis is especially difficult when the diarrheal disorder is atypical (i.e. when there is no or limited skin involvement). In a previous study, we reported the positive impact of wireless video-capsule endoscopy (VCE) in the diagnosis of post-transplant diarrhea. Here, we report our experience over the last 5 years with an overall diagnostic approach (including VCE) to the management of allo-SCT patients with suspected acute GI-GVHD. In addition to wireless VCE, patients with atypical post-transplant diarrhea underwent bacterial and viral investigations and upper and/or lower GI-tract endoscopy (plus biopsies, as appropriate). VCE images were scored according to standard endoscopic classification. The final diagnosis took account of the results of the investigation as a whole and the response to therapy. Between August 2002 and October 2007, 240 patients underwent allo-SCT. Thirty patients underwent 37 extensive investigations, with VCE being performed in the following situations: febrile and/or hemorrhagic diarrhea (n=17), isolated diarrhea (n=15), persistent diarrhea or relapse despite appropriate adjustment of immunosuppressive (IS) treatment (n=5). Median time between allo-SCT and VCE was 50 days (range: 19–197). The final diagnosis was acute GVHD (n=19), viral infection (n=6, with 5 CMVs and 1 HHV6s) and a combination of both in 3 cases. The result of our approach was negative in 9 cases (with a normal GI tract by VCE in 8 of them) who were ultimately diagnosed as having functional diarrhea and recovered without any specific treatment.
We observed 5 (14%) VCE failures, either due to an absence of intestinal passage (n=3) or major GI hemorrhage (n=2). In the other cases, VCE results were concordant with the final diagnosis. It was noteworthy that VCE was superior to biopsies in some cases. Thus, while VCE demonstrated typical GI-GVHD lesions in 8 patients with histological proven GI-GVHD, VCE showed a normal GI tract (n=4) or GI-GVHD features in 8 other cases where the biopsies were uncertain (n=7) or non-contributive (n=1). The response to appropriate treatment was favorable in 20 cases but was unfavorable and required further therapeutic adjustment in 8 cases (7 GVHDs, 1 CMV). Five patients died of GVHD (n=3), HHV6 infection (n=1) or both (n=1). This study confirms that VCE is a more sensitive investigative method than GI-endoscopy and biopsies. This approach enhanced our ability to modulate IS treatments in patients suffering from atypical post-transplant diarrhea. With its apparently high predictive value, routine use of VCE could be of great interest, particularly with a view to avoiding unnecessary digestive biopsies.
Direct visualization of drug behaviors in the upper GI tract via magnetically controlled capsule endoscopy
