Composite tissue allotransplantation
The concept of transplanting tissues for restoration of acquired or congenital deformities is not new. In fact, the first account of transplanting tissue from one individual to another appeared in 348 AD, when the transplantation of a lower extremity by two saints was reported (1). It was not until many centuries later, in 1964, that success in solid organ transplantation led a team of surgeons in Ecuador to perform the first human hand transplant. In this case, the immunosuppression used [azathioprine (AZA) and hydrocortisone] was insufficient and the hand rejected and was subsequently amputated 2 weeks posttransplant (2,3). In the late 1970s and early 80s, three separate groups tested the efficacy of the then revolutionary new drug cyclosporine in preventing rejection of extremity transplants in primates (4–6). Although rejection was suppressed for periods of up to 296 days, in these experiments the skin portion of the transplanted extremities was rejected within the first months after transplantation. The discouraging results in Ecuador, together with these primate studies, caused reconstructive surgeons to abandon further attempts to transplant hands for another decade.
In the early 1990s cyclosporine-AZA steroid-based regimens were used in a series of clinical CTAs to reconstruct nerves, tendons, muscle, bone, joint, and laryngeal defects. However, transplantation of composite tissue allografts with skin was still considered impossible when using this regimen. Finally, in 1997 tacrolimus/mycophenolate mofetil (MMF)/prednisone therapy was reported by our group to have successfully prevented composite tissue allograft rejection, while causing minimal systemic toxicity in a preclinical swine forelimb model. Based on these findings, between 1998 and 1999, teams in Lyon (France), Louisville (KY), and Guangzhou (China) performed the first four successful human hand transplants using tacrolimus/MMF/prednisone combination therapy (7). The early outcomes of these four hand transplants, as well as the first larynx, vascularized bone, joint, nerves, and tendons were presented by the respective transplant teams at the Louisville meeting and are summarized below. For a thorough review, the reader is directed to the December 2000 special issue of Microsurgery (8).