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Summary Composite tissue allotransplantation represents a new discipline in reconstructive surgery. Over the past 10 years, we have performed six human vascularized allogeneic knee transplantations. All of these grafts have been lost within the first 56 months. A histomorphologic assessment of the latest case resulted in the detection of diffuse concentric fibrous intimal thickening and occlusion of graft vessels. Findings are comparable with cardiac allograft vasculopathy. The lack of adequate tools for monitoring graft rejection might have allowed multiple untreated episodes of acute rejection, triggering myointimal proliferation and occlusion of graft vessels. Graft vasculopathy represents an obstacle to long‐term vascularized bone and joint allograft survival, and adequate tools for monitoring need to be developed.

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Summary Transplantation of vascularized knee joints is a novel approach in Composite Tissue Allotransplantation (CTA). In 1996 our group started a clinical knee transplantation project and six transplantations have been performed since. Key problems identified early were the monitoring of acute rejection and choice of an immunosuppressive regime. One graft was lost due to postoperative infection and one due to of noncompliance where the patient discontinued the immunosuppressant regime. In three cases late rejection lead to necrosis and graft dysfunction after 15, 16 and 24 months, respectively. Exit‐strategies were arthrodesis in one patient and Above Knee Amputation in two cases. With retrospective analysis after initial five cases the treatment protocol was improved. The immunosuppressive drug regime was altered, femoral diaphysis and knee joint grafting was combined and a vascularized block of donor skin and subcutaneous tissue was harvested with the graft (sentinel skin graft). The sentinel skin graft enabled us to monitor acute rejection by clinical and histological examination and avoid late rejection by rapid treatment with high dose steroids. In summary, over a four‐year period, one of six allogeneic vascularized knee transplants has survived, one was lost from a surgical site infection, one by noncompliance and three by late rejection. Analysis of our data leads us to suggest that knee transplantation should be limited to a combined injury consisting of extensive loss of cartilage and bone, deficient extensor mechanism and soft tissue and skin defects without any signs of infection. Transplantation should only be taken into consideration as last option before Above Knee Amputation in an otherwise healthy patient under 35 years of age.

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