Addition of Vedolizumab to induction regimen improves long term outcomes in intestinal transplantation

Background: Graft-versus-host disease (GvHD) and chimerism are key concerns in intestinal transplantation (IT), due to a larger burden of lymphocytes compared to other solid organ transplants (SOTs).However, the relationship between chimerism and GvHD is complex and not entirely understood.We report an evolution in strategy in the management of chimerism and GVHD after IT offering insights applicable to other SOTs, potentially improving immunological tolerance and reducing GvHD incidence Methods: Retrospective analysis of prospectively collected data in a single UK adult center performing intestine containing grafts between January 2007 and December 2023.Immunosuppression: Induction: Alemtuzumab and Methylprednisolone.Maintenance: Tacrolimus, steroids and Mycophenolate Mofetil or Azathioprine. Management of GvHDChimerism determination was only sought in response to typical GVHD symptoms (usually a rash) before 2015, but now T-cell chimerism monitoring is more routine.Initially, GvHD treatment involved intensified immunosuppression with alemtuzumab, methylprednisolone alongside Extra-Corporeal Photophoresis (ECP) in GvHD.However, after 2014 following two deaths from GvHD on increasing immunosuppression, we switched to reduction in immunosuppression and careful monitoring and ECP as required with favourable outcomes.Results: 144 patients received 151 intestine containing grafts.Multivisceral Transplant (n=50),Small Bowel (n=52),Liver Small-Bowel (n=33), Modified Multivisceral Transplant (n=16).GvHD was biopsy-proven in 8 (5%), with 4 surviving.7 had peripheral macro-chimerism (upto 85%) without clinical GvHD; one had a non-liver graft.Conclusions: GvHD remains challenging in IT.Reducing immunosuppression with careful monitoring of the graft, appears effective in managing and potentially mitigating GvHD in IT recipients even with significant chimerism.