Ileostomy for steroid-resistant acute graft-versus-host disease of the gastrointestinal tract

Abstract

Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious-and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroidresistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.

Diverting Enterostomy Improves Overall Survival of Patients With Severe Steroid-refractory Gastrointestinal Acute Graft-Versus-Host Disease

“…Therefore, the mortality was mainly due to the complications of ASCT rather than the severity of the causal hematologic disease. Our results are consistent with the outcome of diverting ostomy in patients with a SR stage 4 GI-aGVHD reported for the first time by Turki and coworkers in 2019 33 . Their study included 10 patients (8 adults and 2 children) treated with ileostomy (n = 7), jejunostomy (n = 2), and loop ascendostomy (n = 1).…”

“…Considering these data, we hypothesized that a proximal diverting enterostomy (DE) would allow controlling severe steroid-refractory (SR) GI-aGVHD forms in the distal excluded ileocolonic segment. Recently, Turki and coworkers reported encouraging results of enterostomy in 10 patients experiencing stage 4 GI-aGVHD refractory to high-dose of corticosteroid 33 …”

The Pathology and Physiology of Ileostomy

“…Although less significant, similar results were obtained for IL-4, especially in lamina propria lymphocytes (41). Another study also showed ileostomy-induced immune modulation with a > 50% decrease in activated T cell numbers and an increase in that of regulatory T cells in patients with steroid-resistant acute graft-versus-host disease of the gastrointestinal tract (42). Consistent with this, a lack of luminal stimulation reduces the contact between the immune barrier and foreign antigens, which weakens the ability of the adaptive immunity.…”

Surgical Treatment of Severe Bowel Obstruction as a Rare Complication Following Allogenic Hematopoietic Stem Cell Transplantation

“…Conventional GVHD treatment and antiviral treatment were considered inadequate for further therapy, and the obliterating character of the inflammatory process was of such a nature that surgery was considered as the best therapeutic option. Surgical intervention for intestinal GVHD or other post-allo-HSCT complications is rarely necessary, and only a few cases and minor patient material are reported regarding this treatment approach [17][18][19][20][21][22].…”