Analysis of additional treatment strategies for refractory gastrointestinal graft-versus-host disease

At present, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment strategy for hematological malignancies. Although supportive care for allo-HSCT has improved in recent years, graft-versus-host disease (GvHD) is still a serious condition, even life threatening, after transplantation. GvHD of the gastrointestinal tract (GI GvHD) can cause inferior morbidity and mortality as well as worsen the patient’s systemic status. There have been several reports of initial treatment of both acute and chronic forms of GvHD with corticosteroid therapy. Patients with GI GvHD, who do not respond to initial corticosteroids, require second-line treatment. There have been various reports on second-line therapy options for refractory GI GvHD including anti-thymocyte globulin (ATG), alemtuzumab, mesenchymal stromal cells (MSCs), and intraarterial steroid infusion. However, the most effective therapy for steroid-refractory disease remains controversial.

A group of researchers from the Division of Hematology, Saitama Medical University, Jichi Medical University, Saitama, Japan, retrospectively analyzed the outcomes of patients with GI GvHD in their institution and discussed the benefit of an additional treatment strategy for steroid refractory GI GvHD. The research group reviewed the clinical charts of patients who underwent allo-HSCT at their center between May 2007 and May 2017. The study was published in Annals of Hematology.

Patient characteristics:

• N = 68 cases with GI GvHD
• Median age at transplantation: 47.5 years (range, 16–68)

Key findings:

• 1-year overall survival was significantly inferior in patients who did not respond to first-line treatment: 27.3% vs 69.2%, P = 0.0017
• 1-year progression-free survival was significantly lower in patients who did not respond to the first-line treatment: 23.5 vs 64.2%, P = 0.0018
• Non-relapse mortality was inferior in patients who did not respond to first-line treatment: 50.0 vs 18.6%, P = 0.026
• Eighteen patients were refractory to all steroid-based treatments such as steroid pulse therapy and oral beclomethasone dipropionate (BDP)
• Steroid-refractory patients receiving steroid only showed an increased response rate after the initial diagnosis of steroid refractoriness

Diagnosis and follow-up with colonoscopy:

• Fifty-two cases were diagnosed as lower GI GvHD, of these, 18 patients underwent repeated colonoscopy for prolonged diarrhea
• Median duration from the diagnosis of GI GvHD to the first follow-up colonoscopy: 38 days (range, 13–178)
• Median time of follow-up colonoscopy: 2 (range, 1–7)
• In the steroid refractory group, colonoscopy was repeated in 12/18 patients
• Detected conditions other than GvHD in 11/18 patients: CMV colitis, thrombotic microangiopathy, and post-transplant lymphoproliferative disease

In summary, in the observed steroid-refractory patients with GI GvHD, clinical outcomes were inferior. However, in steroid refractory patients the response rate significantly improved without additional immunosuppressants after the diagnosis of steroid refractoriness. The authors state that "these later responses may be explained by the problem of evaluating the response based solely on the volume of diarrhea. Severe mucosal damage due to refractory GI GVHD may require a longer recovery even after the sufficient inhibition of immunological attack by donor cells." The authors further added that continual colonoscopy is essential in this patient population. Continuous observation and enhanced supportive care might be a feasible option for GvHD patients who are steroid refractory.