*Purpose: Reconstructive transplantation represents a therapeutic option for severe tissue defects which are not amendable to conventional reconstructive attempts. We herein report long-term follow-up data over a period of 18 years (mean 11.2 years).

*Methods: Between March 2000 and March 2014 five patients received a bilateral hand (n=3), bilateral forearm (n=1) and a unilateral hand (n=1) transplant performed at the Medical University of Innsbruck. Antithymocyte globulin or alemtuzumab was used for induction therapy, followed by triple (tacrolimus/prednisolone/mycophenolate mofetil) or dual (tacrolimus/mycophenolate mofetil) immunosuppression.

*Results: Hand function and sensitivity continuously improved during the first five years and remained stable with insignificant fluctuations thereafter. To reduce the burden of calcineurin inhibitors, m-TOR inhibitors (n=2/5) and belatacept (n=3/5) were added to the therapeutic regimen. At total of 38 rejection episodes was observed. The majority were cellular rejections (65,79%), while 11 (28.85%) were identified as antibody-mediated rejections (AMR) with presence of donor-specific alloantibodies (DSA). AMR manifested both early and late after transplantation. While it was successfully treated in two patients with anti-CD25, IVIG and immunoadsorption, the hand allograft of the unilateral transplant recipient had to be amputated at seven years after multiple, unmanageable AMRs with significant levels of DSAs, eventually resulting in severe allograft vasculopathy, and hence chronic rejection. The same patient was diagnosed with stage IV gastric adenocarcinoma 12 months after graft removal and passed away six months after diagnosis. The remaining four patients are currently rejection-free with moderate levels of immunosuppression and without any evidence of chronic rejection.

*Conclusions: In immunologically stable patients, the introduction of belatacept was able to help reduce overall burden of immunosuppressive therapy. AMR is challenging, and early de-novo DSA was associated with a complex immunological course.

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