A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow transplantation

Snover, Dale C.; Weisdorf, Sally A.; Vercellotti, Gregory M.; Rank, Brian H.; Hutton, Scot W.; McGlave, Philip B.

doi:10.1016/s0046-8177(85)80232-x

Cited by 163 publications

(102 citation statements)

References 7 publications

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“…Patients with severe cGVHD may also present with wasting or failure to thrive, which may improve with effective immunosuppressive therapy. 8,9 We describe four cases with a common clinical presentation of malabsorption secondary to pancreatic insufficiency. In all cases, the symptoms were initially felt to be due to gut GVHD because of the absence of infectious causes and the presence of cGVHD.…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted, however, that the histopathologic diagnosis of chronic gut GVHD may be difficult to make with muscosal biopsies because fibrosis and other histologic findings including mononuclear cell infiltration and sclerosis and hyalinization of small venules are usually confined to the submucosa and subserosa. 9 After infection and gut GVHD have been excluded, the cause of diarrhea seen in these four patients was considered to be either due to an unidentified small bowel mucosal etiology or pancreatic insufficiency potentially from chronic pancreatitis. The likelihood of pancreatitis was of particular importance in the first case because of a previous history of abdominal trauma and atrophic pancreas on the CT scan.…”

Section: Discussionmentioning

confidence: 99%

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Pancreatic insufficiency in patients with chronic graft-versus-host disease

Akpek

Valladares

Lee

et al. 2001

Bone Marrow Transplant

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Summary:Diarrhea is a difficult diagnostic problem in patients with chronic graft-versus-host disease (cGVHD) because there are many causes of it. Although intestinal involvement has been reported in early studies of untreated cGVHD, this is now a very rare presentation of the disease. In addition to other etiologies, pancreatic insufficiency should also be considered in patients with cGVHD who demonstrate malabsorption. The pathogenesis of pancreatic insufficiency in these patients is unknown. Pancreatic enzyme supplements can be very effective in treating this rare condition. Bone Marrow Transplantation (2001) 27, 163-166. Keywords: chronic GVHD; malabsorption; diarrhea; pancreas; pancreatic insufficiency Although the incidence of diarrhea falls after day 100 following hematopoietic stem cell transplantation, it can still be a problem, particularly in patients with ongoing graftversus-host disease (GVHD). 1,2 The most common cause of diarrhea in long-term transplant survivors is infection because of the incomplete immune reconstitution in the majority of these patients, especially in those with cGVHD. [2][3][4][5][6] Although intestinal involvement in patients with untreated cGVHD was described in early studies, this is now a very rare phenomenon because of the widespread use of potent immunosuppressive(s) in the treatment of extensive cGVHD. The lower gastrointestinal (GI) tract, particularly the small bowel, is less frequently affected by cGVHD than the esophagus. The diagnosis of GI involvement by cGVHD requires extensive evaluation to rule out other causes of malabsorption or maldigestion. 5,6 In this report, we present four cases with unexplained diarrhea masquerading as chronic gut GVHD. Case reports Case oneA 38-year-old white male with chronic myelogeneous leukemia in chronic phase underwent allogeneic bone marrow transplantation (BMT) from his HLA-identical sibling following a busulfan/cyclophosphamide conditioning regimen. His past history was significant for abdominal trauma due to a motor vehicle accident. Approximately 3 months after his BMT, the patient developed a skin rash, oral lichenoid changes and dry eye symptoms, which were consistent with chronic GVHD. A skin biopsy was inconclusive but a salivary gland biopsy confirmed the diagnosis of cGVHD. He responded to an immunosuppressive regimen which included steroids, cyclosporine and PUVA.At the 6 month follow-up visit, he was noted to have abdominal discomfort, bloating and nausea, which did not improve with an H-2 receptor blocker, omeprazole, propulsid or ondansetron. An esophagogastroduedenoscopy (EGD) was unremarkable. Gastric and duodenal biopsies were negative for GVHD and any infectious agents. Subsequently, his cGVHD flared with increased oral symptoms associated with lichenoid lesions, skin rash and abnormal liver function tests. Thalidomide was added to cyclosporine and prednisone. Although his cGVHD improved with this therapy, the GI symptoms persisted. At 20 months post BMT, he developed upper abdominal pain and diarrhea. His dia...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pancreatic insufficiency in patients with chronic graft-versus-host disease

Akpek

Valladares

Lee

et al. 2001

Bone Marrow Transplant

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“…2,3,17 CMV infection was diagnosed on the basis of morphologic features which included large cells containing amphophilic intranuclear inclusions, immunopositivity for viral markers, or a positive viral culture. Upper GI GVHD was not diagnosed if epithelial cell necrosis was observed within foci of CMV infection.…”

Section: Histologic Examinationmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8] It has been suggested that clinical features of GVHD differ by geographic area or among races because of different immunogenetic backgrounds. [11][12][13][14] Therefore, the clinical significance of upper GI GVHD in previous reports may not necessarily apply to patients outside the United States.…”

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Prospective evaluation for upper gastrointestinal tract acute graft-versus-host disease after hematopoietic stem cell transplantation

Wakui

Okamoto

Ishida

et al. 1999

Bone Marrow Transplant

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Summary:The incidence and clinical significance of upper gastrointestinal tract acute graft-versus-host disease (upper GI GVHD) were prospectively evaluated in 44 Japanese patients who underwent allogeneic (n = 26) or autologous (n = 18) stem cell transplantation. Endoscopic examination was routinely performed between days 20 and 50 post-transplant and when symptoms of upper GI and/or acute GVHD of other organs were present. The results were compared with the historical records of 49 allograft and 20 autograft recipients. The diagnosis of upper GI GVHD was confirmed by histologic findings of GVHD and persistent upper GI tract symptoms. The incidence of upper GI GVHD was 46% in the prospective allograft group, higher than in the retrospective group. Upper GI GVHD was not diagnosed in any autograft patients. Twelve of 19 patients with upper GI GVHD had skin GVHD, and two of the 12 had concurrent lower GI GVHD. Upper GI GVHD was successfully treated with steroids and did not progress to symptomatic lower GI GVHD. In addition, upper GI GVHD completely resolved without specific alteration in immunosuppressant therapy in six patients. No risk factors for upper GI GVHD could be identified. The presence of upper GI GVHD did not significantly affect early death rate, incidence of chronic GVHD, and overall survival. In conclusion, by the prospective evaluation of the upper GI tract by endoscopy we could accurately diagnose upper GI GVHD in half our allogeneic recipients. However, upper GI GVHD was successfully controlled with or without additional steroids in all cases and had little impact on transplant outcome.

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Role of apoptosis in gastric epithelial turnover

Herbay

Rudi

2000

Microsc. Res. Tech.

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Gastric epithelial turnover is a dynamic process. It is characterized by continous cell proliferation, which is counterbalanced by cell loss. The biological principle that mediates the homeostasis of epithelium is programmed cell death, or apoptosis. Currently, several subtypes of apoptosis are distinguished, which are mediated by different mechanisms. Various subtypes of apoptosis also occur in the gastric epithelium under various conditions. In the normal stomach, apoptosis due to cell isolation (anoikis) mediates the physiological epithelial turnover. Albeit rarely seen in routine histology, approximately 2% of epithelial cells in the normal stomach are apoptotic. In Helicobacter pylori‐induced gastritis, apoptosis and epithelial proliferation are moderately increased, with approximately 8% apoptotic epithelial cells. In gastritis, factors such as CD95 ligand or tumor necrosis factor (TNF) alpha act as death factors. They bind to specific receptors, CD95 and TNF‐R, which are induced either by other cytokines, such as interferon gamma, or by Helicobacter pylori itself. In addition to CD95, H.pylorican also induce upregulation of CD95 ligand expression. Taken together, the upregulated expression of CD95, and the presence of CD95L in the close proximity to apoptotic gastric epithelial cells suggest a functional role of the CD95‐CD95L system in the induction of apoptosis in H.pylori‐gastritis. The role of other pathways to apoptosis is currently under study. Apart from being a biological phenomenon, apoptosis in the stomach may also have direct clinical consequences. An extreme example is given in gastric graft‐vs.‐host disease when epithelial denudement occurs. Microsc. Res. Tech. 48:303–311, 2000 © 2000 Wiley‐Liss, Inc.

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A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow transplantation

Cited by 163 publications

References 7 publications

Pancreatic insufficiency in patients with chronic graft-versus-host disease

Pancreatic insufficiency in patients with chronic graft-versus-host disease

Prospective evaluation for upper gastrointestinal tract acute graft-versus-host disease after hematopoietic stem cell transplantation

Role of apoptosis in gastric epithelial turnover

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