Outcomes 18 Months after the First Human Partial Face Transplantation

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Abstract

We performed the first human partial face allograft on November 27, 2005. Here we report outcomes up to 18 months after transplantation. The postsurgical induction immunosuppression protocol included thymoglobulins combined with tacrolimus, mycophenolate mofetil, and prednisone. Donor hematopoietic stem cells were infused on postoperative days 4 and 11. Sequential biopsy specimens were taken from a sentinel skin graft, the facial skin, and the oral mucosa. Functional progress was assessed by tests of sensory and motor function performed monthly. Psychological support was provided before and after transplantation. Sensitivity to light touch, as assessed with the use of static monofilaments, and sensitivity to heat and cold had returned to normal at 6 months after transplantation. Motor recovery was slower, and labial contact allowing complete mouth closure was achieved at 10 months. Psychological acceptance of the graft progressed as function improved. Rejection episodes occurred on days 18 and 214 after transplantation and were reversed. A decrease in inulin clearance led to a change in immunosuppressive regimen from tacrolimus to sirolimus at 14 months. Extracorporeal photochemotherapy was introduced at 10 months to prevent recurrence of rejection. There have been no subsequent rejection episodes. At 18 months, the patient is satisfied with the aesthetic result. In this patient who underwent the first partial face transplantation, the functional and aesthetic results 18 months after transplantation are satisfactory. Copyright 2007 Massachusetts Medical Society.

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Human hand allograft: report on first 6 months.

Marwan Dawahra, H Kapila, G Herzberg … (1999)

Long-term survival of animal limb allografts with new immunosuppressant combinations and encouraging results of autologous limb replantations led us to believe that clinical application of hand transplantation in human beings was viable. On Sept 23, 1998, we transplanted the right distal forearm and hand of a brain-dead man aged 41 years on to a man aged 48 years who had had traumatic amputation of the distal third of his right forearm. The donor's arm was irrigated with UW organ preservation solution at 4 degrees C, amputated 5 cm above the elbow, and transported in a cool container. We dissected the donor limb and the recipient's arm simultaneously to identify anatomical structures. Appropriate lengths of viable structures were matched. Transplantation involved bone fixation, arterial and venous anastomoses (ischaemic time 12.5 h), nerve sutures, joining of muscles and tendons, and skin closure. Immunosuppression included antithymocyte globulins, tacrolimus, mycophenolic acid, and prednisone. Maintenance therapy included tacrolimus, mycophenolic acid, and prednisone. Follow-up included routine post-transplant laboratory tests, skin biopsies, intensive physiotherapy, and psychological support. The initial postoperative course was uneventful. No surgical complications were seen. Immunosuppression was well tolerated. Mild clinical and histological signs of cutaneous rejection were seen at weeks 8-9 after surgery. These signs disappeared after prednisone dose was increased (from 20 mg/day to 40 mg/day) and topical application of immunosuppressive creams (tacrolimus, clobetasol). Intensive physiotherapy led to satisfactory progress of motor function. Sensory progress (Tinel's sign) was excellent and reached the wrist crease (20 cm) on day 100 for the median and ulnar nerves, and at least 24 cm to the palm by 6 months when deep pressure, but not light touch sensation, could be felt at the mid palm. Hand allotransplantation is technically feasible. Currently available immunosuppression seems to prevent acute rejection. If no further episode of rejection occurs, the functional prognosis of this graft should be similar to if not better than that reported in large series of autoreconstruction.

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First human face allograft: early report.

Cédric D'Hauthuille, Lionel Badet, Sylvie Testelin … (2006)

Extended soft tissue defects of the face are difficult to reconstruct, and autologous tissue transfers usually lead to poor cosmetic and functional outcomes. We judged that composite tissue transplantation could be valuable in facial reconstructive surgery. We transplanted the central and lower face of a brain-dead woman onto a woman aged 38 years who had suffered amputation of distal nose, both lips, chin, and adjacent parts of the cheeks. Transplantation consisted of revascularisation of right and left facial arteries and veins (ischaemic time 4 h), mucosal repair of oral and nasal vestibules, bilateral anastomoses of infraorbital and mental sensitive nerves, joining of mimic muscles with motor nerve suture on mandibular branch of the left facial nerve, and skin closure. Immunosuppressive treatment was with thymoglobulin, tacrolimus, mycophenolate mofetil, and prednisone. Two infusions of donor bone-marrow cells were given. Follow-up included routine tests, biopsies, physiotherapy, and psychological support. The initial postoperative course was uneventful. No surgical complication occurred. Bone-marrow graft and immunosuppression were well tolerated. Mild clinical signs of rejection were seen at day 20. Increased corticoids initially did not reverse rejection, but signs of rejection disappeared after three boluses of prednisone. Anatomical and psychological integration and recovery of sensation were excellent. At the end of the first postoperative week, the patient could eat, and speech improved quickly. Passive transmission of muscle contractions to the graft already exists; physiotherapy is being done to restore dynamic motions around the lips. The 4-month outcome demonstrates the feasibility of this procedure. The functional result will be assessed in the future, but this graft can already be deemed successful with respect to appearance, sensitivity, and acceptance by the patient.

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Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction.

E Quelvennec, G Semana, Mehdi ALIZADEH … (2002)

We have developed a real-time quantitative polymerase chain reaction (PCR) assay using TaqMan technology (Applied Biosystems, Foster City, CA) for monitoring donor cell engraftment in allogenic hematopoietic stem cell transplant recipients. For this purpose, we selected 19 specific sequence polymorphisms belonging to 11 human biallelic loci located on 9 different chromosomes. Using a set of specially designed primers and fluorogenic probes, we evaluated the 19 markers' informativity on a panel of 126 DNA samples from 63 recipient/donor pairs. In more than 90% of these pairs, discrimination between recipient and donor genetic profile was possible. By using serial dilutions of mixed DNAs, we evaluated the linearity and sensitivity of the method. A linear correlation with r higher than 0.98 and a sensitivity of 0.1% proved reproducible. Fluorescent-based PCR of short tandem repeats (STR-PCR) and real-time PCR chimerism assay were compared with a panel of artificial cell mixtures. The main advantage of the real-time PCR method over STR-PCR chimerism assays is the absence of PCR competition and plateau biases, and results evidenced greater sensitivity and linearity with the real-time PCR method. Furthermore, different samples can be tested in the same PCR run with a final result in fewer than 48 hours. Finally, we prospectively analyzed patients who received allografts and present 4 different clinical situations that illustrate the informativity level of our method. In conclusion, this new assay provides an accurate quantitative assessment of mixed chimerism that can be useful in guiding early implementation of additional treatments in hematopoietic stem cell transplantation.