Patients

All patients provided written informed consent to participate in the clinical trial (ClinicalTrials.gov number, NCT01281267) for face transplantation, as approved by the human research committee at Brigham and Women's Hospital and by the Army Medical Research and Materiel Command Human Research Protection Office.

Table 1. Table 1. Selected Characteristics of the Donors and Patients.

Figure 1. Figure 1. Photographs of the Three Patients before Transplantation and Immediately and Several Months after Surgery. Shown is the preoperative appearance (left column), immediate postoperative appearance (middle column), and appearance after surgery (right column) at 4 months (Patient 1), 3 months (Patient 2), and 2 months (Patient 3). All patients provided written consent for publication of their photographs.

All patients were evaluated by our multidisciplinary team before participation.10,11 Their medical histories are summarized in Table 1. Pretransplantation frontal photographs are shown in Figure 1, and pretransplantation profile photographs are shown in Figure 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org.

After extensive discussion of the indications, risks, and benefits, which included input from an ethicist, treatment by full-face transplantation was elected by all three patients in an attempt to enhance function and appearance. The New England Organ Bank identified and obtained consent for organ donation from families of suitable brain-dead donors who were matched with the patients according to sex and skin color. In addition, donors and recipients were matched on the basis of several clinical characteristics (Table 1), including negative T- and B-cell cross-matching. Our surgeons were divided into teams with specific objectives during the operations.

Transplantation Procedures

In each instance, one team performed facial allograft recovery that isolated all major motor and sensory nerves and arterial and venous components (Table 1 in the Supplementary Appendix). Another team recovered radial forearm flaps to act as sentinel tissue from Donors 1 and 2. Another two teams recovered the upper limbs from Donor 3. All recovered allografts were perfused with University of Wisconsin solution and transported in an ice-water slurry.

In synchronization with the donor operation, another team removed the skin, contoured the facial tissue remnants, and isolated bilateral motor- and sensory-nerve branches and neck vessels of the recipient. The residual functioning portions of the recipients' faces were preserved to allow them to return to their pretransplantation level of function in the event of transplant failure.11 All facial-nerve branches and sensory nerves were anastomosed unless they were not present because of injury (Table 1 in the Supplementary Appendix). Donor skin was tailored to the recipients' defects for optimal contour. All facial allografts had complete perfusion after implantation.

Table 2. Table 2. Timing of Selected Interventions and Events after Full-Face Transplantation.

A third team transplanted the sentinel skin flaps to an inconspicuous area (in Patient 1) and to a hand contracture (in Patient 2); Patient 3 underwent simultaneous bilateral transplantation of the upper limbs, a procedure that is not described in detail in this report. The patients were initially treated in the intensive care unit and were subsequently transferred to the surgical ward until discharge (Table 2).

Immunosuppression

All patients received mycophenolate mofetil, methylprednisolone, and rabbit antithymocyte globulin before allograft reperfusion. Maintenance immunosuppression consisted of mycophenolate mofetil, tacrolimus, and prednisone taper (Table 2, and Fig. 2 in the Supplementary Appendix). We obtained skin-biopsy samples from facial and sentinel allografts periodically and during suspected rejection (Table 2). Biopsy samples were graded according to the Banff 2007 scale.12 Immunosuppression was adjusted on the basis of clinical judgment, biopsy results, and tacrolimus trough levels (Table 2). Perioperative antibacterial prophylaxis consisted of vancomycin and cefazolin and was modified according to perioperative findings; Patients 2 and 3 also received perioperative antifungal prophylaxis with micafungin. All patients received trimethoprim–sulfamethoxazole and valganciclovir prophylaxis against Pneumocystis jirovecii and cytomegalovirus, respectively, for at least 6 months.

Postoperatively, all patients had tracheotomies placed; these were removed within 3 months in all cases. All patients had access to continuous counseling from psychiatrists and social workers.