Ileostomy As a Treatment Option in Patients with Refractory Acute Gastro-Intestinal Graft Versus Host Disease
Authors: Guidez Stéphanie , Coiteux Valerie , Gerard Romain , Dulery Remy , Magro Leonardo , Yakoub-Agha Ibrahim , Saudemont Alain , Seguy David 
Published: October 2019

Abstract
Introduction: Treatment of refractory gastro-intestinal GVHD (rGI-GVHD) is still disappointing. Indeed, combination of or escalating dose of immunosuppressive treatments not only have no beneficial effects on disease progression but also are responsible for an increased risk of infections with short-term survival rate less than 20%. GI surgery has been for long time offered to patients with Crohn disease; this approach is usually restricted to patients with GVHD-related GI occlusion. Given the similarity between the two diseases, and the predominance of GI-GVHD damages in the distal part of the small bowel, we have considered surgery in 8 patients with rGI-GVHD. We performed an end ileostomy in order to circumvent the affected portion of the intestine and limit the use of immunosuppressive treatment. Here, we report our experience on patients with rGI-GVHD who underwent GI-surgery.
Methods: Eight patients with acute grade 4 GVHD according to standard criteria were retrospectively analyzed. First line treatment consisted of steroids at the dose of 2 mg/kg/day for all patients. Second-line therapy consisted of anti-IL2R monoclonal antibodies (n=6) or anti-thymocyte globulin (n=2). Six patients had received 2 lines of therapy before surgery while 1 had received 4 lines and 1 after 5 lines. The diagnosis of acute GI-GVHD was confirmed by comprehensive GI examination including upper and lower endoscopies with biopsies, wireless video-capsule endoscopy and investigation for eliminate infection. In addition, barium small follow-through was performed to evaluate the extension of the GI damages before surgery in order to guide the intervention. After surgery, oral feeding was encouraged and patients received both enteral and parenteral nutrition until GI-lesions recovery and restoration of intestinal continuity with end-to-end anastomosis.
Results: Table 1 summarizes patient's characteristics and outcome. The median occurrence of aGVHD was 30 days (25-34) from transplant. Four patients are alive and GVHD free, 81, 71, 11 and 6 months after transplant. The first patient underwent an initial resection of 150cm of distal ileum with immediate intestinal continuity restoration for a progressive obstructive syndrome. The other patients had proximal ileostomy at 100 cm to 150cm after the post duodenal angle. For one patient, perendoscopic gastrostomy was also realized during surgery to simplify enteral nutrition. Two patients (#4 and #5) died of infections 6 and 13 days after surgery. They were in very bad condition at surgery. Patient #3 who improved his GVHD after surgery, died 225 days later of severe flu infection.
Conclusion: Despite its limited size, this cohort of patients with severe rGI-GVHD treated with ileostomy appears promising. Whenever possible, this original and multidisciplinary approach should be considered in patients with grade IV rGI-GVHD after 2 lines of immunosuppressive treatment. A prospective study will start soon to evaluate the safety and efficacy of GI surgery in GI-GVHD after one line of therapy.
Table 1: Patients and GVHD characteristics and outcome. # Age Gender Onsetof aGVHDfrom transplant(Days) Number of Prior line of immunosuppressive therapy(Lines) Time of surgery from GVHD (Days) Outcome(Time from transplant) 1 41 1 30 2 185 Alive, GVHD-free (81 months) 2 46 2 30 4 93 Alive, GVHD-free (71 months) 3 61 2 30 2 140 Dead (13months) 4 33 1 26 5 64 Dead (3 months) 5 27 2 25 2 49 Dead (3 months) 6 44 2 34 2 22 Alive, GVHD-free (11 months) 7 21 1 30 2 25 Dead (4 months) 8 33 1 35 2 120 Alive, GVHD free (6 months)

Disclosures
No relevant conflicts of interest to declare.