Scott A. Gruber

Successful Hand Transplantation — One-Year Follow-up

Background On the basis of positive results in studies of the transplantation of pig extremities and the information exchanged at an international symposium on composite-tissue transplantation, we developed a protocol for human hand transplantation. Methods After a comprehensive pretransplantation evaluation and informed-consent process, the left hand of a 58-year-old cadaveric donor, matched for size, sex, and skin tone, was transplanted to a 37-year-old man who had lost his dominant left hand 13 years earlier. Immunosuppression consisted of basiliximab for induction therapy and tacrolimus, mycophenolate mofetil, and prednisone for maintenance therapy. Results The cold-ischemia time of the donor hand was 310 minutes. There were no intraoperative or early postoperative complications. Moderate acute cellular rejection of the skin of the graft developed 6, 20, and 27 weeks after transplantation. All three episodes resolved completely after treatment with intravenous methylprednisolone and topical tacrolimus...

Infectious complications after kidney transplantation: current epidemiology and associated risk factors

Abstract:u2002 Background:u2002 The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied.

Long-term survival of an extremity composite tissue allograft with FK506-mycophenolate mofetil therapy.

BACKGROUNDnHigh-dose tacrolimus (FK506) monotherapy has significantly prolonged rat hindlimb allograft survival. With an eye toward direct clinical application, we used a large-animal extremity composite tissue allograft model to assess the antirejection efficacy and systemic toxicity of combination FK506-mycophenolate mofetil (MMF) treatment.nnnMETHODSnRadial forelimb osteomyocutaneous flap transplants were performed between size-matched outbred pigs assigned to one of two groups: 5 control pigs received no immunosuppression and 9 animals received a once-daily oral FK506-MMF-prednisone regimen. Rejection was assessed by visual inspection of flap skin and was correlated with serial histopathologic examination of skin biopsy specimens.nnnRESULTSnIn all control pigs the flap was completely rejected on day 7. Of the 9 pigs receiving treatment, 3 died from pneumonia on days 29, 30, and 83 without signs of rejection and another died from gastric rupture on day 42 with persistent mild rejection. The remaining 5 animals were free of rejection at the end of the 90-day follow-up period (P < 0.005 vs controls). Overall, 5 pigs had pneumonia, 4 septic arthritis, 3 toe abscesses, and 5 diarrhea and decreased weight gain.nnnCONCLUSIONSnCombination oral FK506-MMF treatment provided a superior antirejection effect but more produced more toxicity than that previously demonstrated with cyclosporin A-MMF therapy in our model. Our results suggest that reduction of FK506 or MMF doses might decrease both infectious and drug-specific side effects while still providing adequate prophylaxis against rejection.

LOCAL DRUG DELIVERY TO COMPOSITE TISSUE ALLOGRAFTS

Unlike visceral solid-organ transplants, composite tissue allografts (CTA) are modules composed of various tissues, each with differing antigenicity, and therefore differing potential for rejection.1 Skin and muscle (and perhaps synovium) are the most antigenic and appear to be most susceptible to rejection, while bone, tendon, cartilage, and neurovascular tissue appear to be less immunogenic and evoke rejection responses of lower magnitude. Although CTA have tremendous potential clinical application for functional and structural reconstruction of major congenital and acquired peripheral tissue defects, these transplants, until recently, have remained one of the last frontiers in clinical organ transplantation because of concerns regarding their risk/benefit ratio.2,3 Two questions address the key issues involved: (1) Can rejection of these highly antigenic tissues be prevented using currently available immunosuppressive regimens with acceptable drug-specific and generalized toxicity? and (2) Will function be restored to a significant degree so as to justify the surgical and immunosuppressive risks involved? The information presented at the Second International Symposium on Composite Tissue Allotransplantation (Louisville, May, 18–19, 2000) has begun to shed some light on the answers to these questions. The recipients of hand transplants in Lyon (two patients), Louisville (one patient), and Guangzhou (two patients) all received a form of antilymphocyte antibody for induction (antithymocyte globulin and/or an interleukin-2 receptor [IL-2R] antagonist), and tacrolimus (FK506), mycophenolate mofetil, and prednisone therapy for maintenance immunosuppression. Despite this clinically acceptable but nonetheless intensive immunosuppressive regimen, akin to that currently utilized for rejection-prone, nonuremic, insulin-dependent diabetics who receive a pancreas transplant,4 the first Lyon patient sustained an episode of acute rejection at 8 weeks and the Louisville recipient developed moderate acute cellular rejection at 6, 20, and 27 weeks posttransplant.5,6 Although all these episodes resolved completely after combination systemic pulse steroid and topical FK506-clobetasol treatment, the transient increase in oral with or without intravenous (IV) prednisone and FK506 doses during and after each rejection episode further increased the already elevated immunosuppressive burden in these patients. Along these lines, the Louisville recipient developed tissue-invasive cytomegalovirus disease at 15 weeks posttransplant, requiring subsequent long-term ganciclovir prophylaxis. These preliminary results suggest that clinical application of CTA is more likely to gain widespread acceptance if the systemic immunosuppressive burden and its attendant long-term risks of infection, malignancy, and drug-specific side effects could be reduced while simultaneously preventing rejection and maintaining function.