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Annals of Hematology

, Volume 98, Issue 10, pp 2407–2419 | Cite as

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

  • Amin T. TurkiEmail author
  • Evren Bayraktar
  • Oliver Basu
  • Tamas Benkö
  • Ji-Hee Yi
  • Jan Kehrmann
  • Asterios Tzalavras
  • Tobias Liebregts
  • Dietrich W. Beelen
  • Nina K. Steckel
Original Article

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.

Keywords

Hematopoietic stem cell transplantation Graft-versus-host disease Refractory GVHD Intestinal adaptation Ileostomy-induced immune modulation Intestinal microbiota 

Notes

Acknowledgments

We would like to thank Dr. Stefanie Bertram for advice on intestinal histopathology, Prof. Katharina Fleischhauer for critical review of the manuscript, and Martina Franke and all other colleagues of the BMT laboratory for technical assistance. Clinical research was supported by the University of Duisburg-Essen.

Authorship

ATT, NKS, and DWB designed the study. EB and ATT performed statistical analysis. ATT, JY, JK, AT, and OB performed data collection. TB, JK, and TL participated in data acquisition and analysis. ATT, EB, and NKS wrote the manuscript. DWB, TL, and TB contributed to write the manuscript. All authors had access to primary clinical trial data, read, and approved the final manuscript.

Compliance with ethical standards

The study and data acquisition was conducted in accordance with German legislation and the revised Helsinki Declaration and evaluated by the ethical institutional review board of the University of Duisburg-Essen (Protocol No. 18-8220-BO). Written consent to experimental surgical therapy was obtained from all patients with ileostomy. We confirm that no patient can be identified because of anonymized patient data.

Conflict of interest

ATT has received lecture fees from Jazz Pharmaceuticals and travel subsidies from Neovii Biotech outside the submitted work. NKS received travel subsidies from MSD and Jazz, DWB received travel subsidies from Medac, all outside the submitted work. The other authors declare that they have no competing interests.

Supplementary material

277_2019_3754_MOESM1_ESM.pdf (94 kb)
ESM 1 (PDF 94 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Amin T. Turki
    • 1
    Email author
  • Evren Bayraktar
    • 1
  • Oliver Basu
    • 2
  • Tamas Benkö
    • 3
  • Ji-Hee Yi
    • 1
  • Jan Kehrmann
    • 4
  • Asterios Tzalavras
    • 1
  • Tobias Liebregts
    • 1
  • Dietrich W. Beelen
    • 1
  • Nina K. Steckel
    • 1
  1. 1.Department of Bone Marrow Transplantation, West-German Cancer CenterUniversity Hospital EssenEssenGermany
  2. 2.Department of Pediatric Stem Cell Transplantation, Center of Pediatrics IIIUniversity Hospital EssenEssenGermany
  3. 3.Department of General-, Visceral- and Transplantation SurgeryUniversity Hospital EssenEssenGermany
  4. 4.Institute of Medical MicrobiologyUniversity Hospital EssenEssenGermany

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