2017 - CIRTA

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1- Rejection of the Intestine Allograft

15.2 - Early outcomes of a stepwise desensitization strategy to facilitate intestinal transplantation

Presenter: Daryl, Nnani, New York, United States
Authors: Andrew Santeusanio, Daryl Nnani, Angela Templeton, Alyssa Burnham, Jang Moon, Thomas Schiano, Kishore Iyer

Early outcomes of a stepwise desensitization strategy to facilitate intestinal transplantation

Andrew Santeusanio1,2, Daryl Nnani2, Angela Templeton1, Alyssa Burnham1, Jang Moon1, Thomas Schiano1, Kishore Iyer1.

1Intestinal Rehabilitation & Transplantation Program, Mount Sinai Medical Center, New York, NY, United States; 2Pharmacy, Mount Sinai Medical Center, New York, NY, United States

Background: Preformed donor specific antibody (DSA) is associated with a poor outcome after intestinal transplant (ITX): To describe preliminary results from a stratified approach to managing anti-HLA antibody prior to ITX.

Methods: Retrospective review of patients listed for ITX from January 2010-2016. All patients had baseline solid-phase (Luminex) testing done to detect anti-HLA antibody prior to ITX. For patients with panel reactive antibody (PRA) > 30%, desensitization was using a stratified approach (Figure 1). Patients with PRA > 30% were initially treated with standard therapy consisting of IVIG and rituximab. Patients who remained sensitized following standard therapy were treated with bortezomib, a proteasome inhibitor that targets plasma cells. Primary outcoerms were patient and graft survival.

Results: 8 patients received desensitization with baseline PRA > 30%. Three patients with PRA between 30 – 60% were treated with standard therapy alone. Five patients had an inadequate response to standard therapy and received plasmapheresis (PLEX) and bortezomib. 7 of the 8 patients were successfully transplanted after a mean wait-time of 151 days. One patient died on the wait list with persistently high PRA. Post-ITX, 5 patients were found to have a Flow positive cross-match (CMX) but with reasonable allograft survival 5/7 (71.4%) as of 2016. All desensitization therapies were well tolerated with only modest reductions in platelets and one infusion related reaction. Opportunistic infections did occur more frequently in the patients receiving bortezomib (Table 1). Both standard as well as bortezomib based desensitization therapies were associated with reductions in epitope specific anti-HLA antibodies following treatment (44.3% vs 13.6%; Table 2). Of note, bortezomib and PLEX were primarily effective in reducing class II DR and DQ antibodies.

Conclusion: Our preliminary experience with a tiered approach to desensitization allowed for successful transplantation of 7 previouslyhighly sensitized patients. Both standard therapy as well as bortezomib based desensitization were well tolerated, but with a relatively high incidence of opportunistic infections noted with bortezomib. Consequently, a patient centered, risk-stratified approach to desensitization is likely optimal. It may also be prudent to limit ongoing bortezomib use to patients with good functional status and those with primarily class II anti-HLA antibodies.

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