Paeds Haematologic Neoplasms

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

Ann Hematol. 2019 Oct;98(10):2407-2419

Authors: Turki AT, Bayraktar E, Basu O, Benkö T, Yi JH, Kehrmann J, Tzalavras A, Liebregts T, Beelen DW, Steckel NK

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 steroid-resistant 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.

PMID: 31338570 [PubMed - indexed for MEDLINE]

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