P4.60: Bortezomib for the treatment of chronic Graft Versus Host Disease in Intestinal Transplant recipient

Introduction: GVHD is a disparate immunological response between host and recipient tissues. When it occurs after Intestinal Transplantation (ITx), it can be deadly. Bortezomib is a proteasome inhibitor that affects dendritic and T-cell processes essential for the development of GVHD but also decreases B cells. The use of Bortezomib at time of bone marrow transplant (BMT) in mice protected against acute GVHD. Bortezomib has been used in ITx for refractory acute rejection with donor specific antibodies. To our knowledge, we present the 1st use of Bortezomib for chronic GVHD in ITx. Case: 25 yo female with Pseudo-obstruction as a result of Ehlers Danlos received a modified MVT. Induction immunosuppression (ISP) was Antithymoglobulin/Rituximab/Methylpred/Basiliximab and maintenance FK/Everolimus. Blood chimerism was followed serially. She developed a skin rash and persistent fevers on week (wk) 4 post transplant. Chimerism rose from 33% wk 4, 61% wk 5 and 80% wk 6. Endoscopy on wk 5 was negative for rectal chimerism and GHVD. Given ongoing symptoms, Alemtuzumab 30 mg IV x 2 was given for acute GVHD. Chimerism decreased to 1% wk 8 but again rose to 96% wk 11, fluctuating over the next month, 56–96%. A 3rd dose of Alemtuzumab was given wk 15. Chimerism decreased to 2% by 5 months (mn) post transplant. 6 mn post transplant, she developed neutropenia. Given possible bone marrow GVHD, a biopsy was done and negative. She again developed rash with alopecia but managed conservatively with prednisone. Course complicated with BK viremia (5.6 million copies) treated empirically with IVIG and decrease in ISP. 9 mn post transplant, she lost 14 pounds due to high ostomy output. Work up ruled out rejection, allergy and infection except BKV pcr + in bowel biopsy. She started Cidofovir, symptoms improved and blood BKV pcr decreased. 12 mn post transplant, liver enzymes increased and biopsy ruled out GVHD. However, she again presented with skin rash despite chimerism <5%. 14 mn post transplant, Bortezomib was given weekly x 4 for chronic GVHD. Thereafter, rash resolved in 4 weeks with no recurrence now 2 years post transplant. Discussion: GVHD continues to be a threat to ITx recipients with high mortality. Diagnosis is notoriously difficult as biopsies tend to be negative early in the course. A strong index of suspicion is necessary, before life threatening organ involvement develop, as early treatment is key to survival. Bortezomib may be an option for chronic GVHD in ITx.