Face Transplantation In A Highly Sensitized Recipient
Anil Chandraker, MD, Ramon Arscott, MD, George Murphy, MD, Christine Lian, MD, Ericka M. Bueno, PhD, Francisco Marty, MD, Stefan Tullius, MD, PhD, Bohdan Pomahac, MD, Helmut Rennke, MD.
Brigham and Women's Hospital, Boston, MA, USA.
PURPOSE: Vascularized composite-tissue allotransplantation (VCA) had not been attempted in patients with high immune sensitization due to concerns of rejection and allograft loss. We performed facial allotransplantation in a highly sensitized recipient with positive pre-operative donor-recipient crossmatch and hereby report our experience.
METHODS: A 45-year-old female presented with a history of extensive chemical burns and more than 50 conventional reconstructive procedures (Figure 1). She had high levels of circulating anti-HLA antibodies, with a calculated panel reactive antibody (cPRA) score of 97. Consequently, the patient remained on the face transplant wait list for 14 months, during which time numerous donors were presented to the team, but rejected after flow crossmatches were found positive. A decision was then made to proceed with full face allotransplantation even if the donor was T- and B-cell flow crossmatch positive. A clear plan was devised for tailoring immunosuppression and salvage options in the event of allograft failure. Shortly thereafter, a donor became available.
RESULTS: The operation was uneventful. Plasmapheresis and immunosuppression induction with thymoglobulin were provided and followed by mycophenolic acid, tacrolimus and steroids. Significant swelling of the lower face was noted on post-operative day (POD) 5. Biopsies showed no evidence of cellular rejection (Figure 1), however, donor specific antibodies in blood were stronger when compared with the pre-transplant levels, and continued to rise with evidence of C4d deposits on biopsy. Despite administration of high dose steroids and thymoglobulin, by POD19 BANFF grade III rejection was diagnosed. Thymoglobulin was stopped due to serum sickness. Combination therapy of plasmapheresis, eculizumab, bortezomib, and reduced dose alemtuzumab successfully decreased donor specific antibody levels (Figure 2). The erythema of the allograft slowly subsides. Allograft biopsies taken on POD29 showed both a downgrade to BANFF Grade II rejection and less C4d immunoreactivity. By POD116, biopsies showed no evidence of active cellular or antibody-mediated rejection (AMR) and have remained as such until 6 months post-op.
CONCLUSIONS: Face transplantation in a highly sensitized patient with a positive crossmatch is possible and manageable. This case may constitute the first AMR reported in VCA to date. Further studies are needed to better classify the histology and mechanism of action of AMR in VCA.
Figure 1: Pre-operative (before), immediate post-operative (POD 0), during acute allograft rejection (POD 6) and POD95 photographs.
Figure 2: Histograms showing donor-specific anti-HLA class I and II antibody levels (2a and 2b respectively) in the patient’s serum as determined by Luminex solid phase single antigen assays. Time on the x-axis is not to scale; time points 1 to 5 correspond with post-operative days 0, 20, 32, 39 and 47 respectively.
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