Composite Tissue Allotransplantation: Current Challenges

Department of Surgery, University of Louisville, Louisville, Kentucky, USA.
Transplantation Proceedings (Impact Factor: 0.98). 11/2009; 41(9):3519-28. DOI: 10.1016/j.transproceed.2009.08.052
Source: PubMed


Composite tissue allotransplantation (CTA) in the clinic is taking firm root. Success at hand, face, knee, trachea, and laryngeal transplantation has led to widespread interest and increasing application. Despite this, skepticism is common, particularly in the realm of reconstructive surgeons. The risks of immunosuppression remain a barrier to the advancement of the field, as these are perceived by many to be prohibitive. Significant progress in the field require the development of newer immunosuppressive agents with less toxicity and methods to achieve donor specific tolerance. This review focuses on the current state of CTA-both in the clinic and the laboratory. A thorough understanding of the immunology of CTA will allow the widespread application of this promising field.

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    • "The majority of patients undergoing VCA have received T-cell depleting induction therapy [7]. Despite this aggressive immunosuppressive therapy, episodes of acute rejection have been recorded in 85% of hand and 54.5% of face transplant recipients in the first year after the transplant [9] [10] [11]. Thus the incidence of acute rejection following VCA transplantation is significantly higher than that seen currently with solid organ transplantation—the overall incidence of acute rejection within the first year after renal transplantation is now less than 15% [12]. "
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    ABSTRACT: Successful hand and face transplantation in the last decade has firmly established the field of vascularized composite allotransplantation (VCA). The experience in VCA has thus far been very similar to solid organ transplantation in terms of the morbidity associated with long-term immunosuppression. The unique immunological features of VCA such as split tolerance and resistance to chronic rejection are being investigated. Simultaneously there has been laboratory work studying tolerogenic protocols in animal VCA models. In order to optimize VCA outcomes, translational studies are needed to develop less toxic immunosuppression and possibly achieve donor-specific tolerance. This article reviews the immunology, animal models, mixed chimerism & tolerance induction in VCA and the direction of future research to enable better understanding and wider application of VCA.
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    ABSTRACT: From its origination involving successful rat hind-limb allograft studies using cyclosporine, face and upper extremity composite tissue allotransplantation has since developed into an exciting and promising subset of reconstructive transplant surgery. Current surgical technique involving composite tissue allotransplantation has allowed optimal outcomes in patients with massive facial and/or upper extremity defects; however, with its coexisting immunologic barrier, obligatory lifelong immunosuppression commits each patient to a daily risk of transplant-related complications with many unanswered questions. Since 1998, nearly 50 hand transplantations in 40 patients have been performed around the world at various levels ranging from wrist level to shoulder level. However, the risk-to-benefit ratio remains controversial in bilateral versus unilateral transplantation and has yet to be determined. From recent experience, the two most important determinants of the success of each patient's upper extremity transplant are patient compliance and intense rehabilitation. A total of nine face transplants have been performed since 2005. Multiple aesthetic subunits (i.e., nose, lips, eyelids) with or without underlying craniofacial skeletal defects (i.e., maxilla, mandible) have been successfully restored, thereby providing restoration of vital facial functions (i.e., smiling) in an unprecedented manner. As of today, face transplantation carries an estimated 2-year mortality of 20 percent. Concomitant composite tissue allotransplantation, which involves a variable combination of allograft subtypes, has been performed in two of the nine face transplant patients. These have included simultaneous bilateral hand transplants and tongue with mandible. Future study is warranted to investigate the potential advantages and disadvantages of using this approach versus a staged approach for reconstruction.
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