Composite tissue allotransplantation (CTA), also known as reconstructive transplantation or vascularized composite allografts (VCAs), involves multiple tissues (skin, muscle, tendon, bone, cartilage, fat, nerves and blood vessels). The primary applications of this type of transplantation have been of the hand and face (partial and full). Federal regulations for CTA, through the Organ Procurement Transplant Network (OPTN), became effective in July 2014. Composite tissue allotransplantation is not considered life-saving, and its primary goal is to increase the individual's quality of life by providing a more normal appearance and a sense of wholeness.
Hand and face transplants have been shown to be technically feasible. The most commonly performed face transplant procedure has been to restore the lower two-thirds of facial structure, especially the perioral area (i.e., lips, cheeks, chin) and in some cases the forehead, eyelids, and scalp. Facial transplantation has been performed on individuals whose faces have been disfigured by trauma, burns, disease, or birth defects and who are unable to benefit from traditional surgical reconstruction. Hand transplantations have been done in individuals who lost a hand due to trauma or life-saving interventions that caused permanent injury to the hand. To date, hand transplants have not been performed for congenital anomalies or loss of a limb due to cancer.
COMPOSITE TISSUE ALLOTRANSPLANTATION OF THE HAND(S)
The most comprehensive worldwide experience with hand and upper-limb transplant was published by Shores, et al in 2015. The study involved 72 individuals, 37 of whom received bilateral transplants and 35 unilateral, for a total of 109 transplanted hand/upper extremities. There are 4 known mortalities: 1 occurred after a bilateral hand transplant; the other 3 followed multitype composite tissue allotransplantations (CTAs; i.e., combined upper- and lower-limb or combined upper-limb and face transplants). Twenty-four graft losses have been reported; 8 of these were also associated with multiple CTA procedures and another 7 occurred in China during their early experience with hand transplantation.
In the United States, 21 known individuals have undergone isolated upper-limb transplantation; 13 were unilateral and 8 were bilateral (limb or digit) procedures. There was 1 immediate graft loss of the bilateral transplanted limb/digit. An additional 3 individuals experienced hand loss at 9 months, 2 years, and 4 years post-transplant. There is sparsely reported data on functional outcomes following hand transplantation. The authors noted that there is a lack of agreement on appropriate outcome measures, and the level of transplantation varies greatly among individuals, making it difficult to compare functional improvement.
An article describing data from the International Registry on Hand and Composite Tissue Allotransplantation was published in 2011 and reported 39 individuals who underwent hand transplants. The article stated that 85% of transplant recipients experienced at least 1 episode of acute rejection in the first year after transplant. Acute rejection episodes were reversible in all individuals compliant with treatment. The most commonly reported complications were metabolic complications (35/39 [90%]) and opportunistic infections (30/39 [77%]). Transient hyperglycemia occurred in 17 (44%) individuals and cytomegalovirus reactivation in 10 (26%) individuals. Ten individuals required surgery for complications (2 arterial thromboses, 1 venous thrombosis, 6 small area of skin necrosis, 1 venous fistula). Five cases of graft loss were reported between day 5 and day 275 following transplant. The early (day 5) graft loss occurred in an individual who underwent face and bilateral hand transplant, and this individual died at day 65 from cerebral anoxia. This was the only reported death in this series of individuals. Hand function was reported in the article, but specific numbers (e.g., mean function scores) were not included. No studies comparing health outcomes in individuals undergoing hand transplantation versus those who received hand/upper-limb prostheses were identified.
COMPOSITE TISSUE ALLOTRANSPLANTATION OF THE FACE
The first successful full face transplant occurred in 2010 in Spain, with the first partial face transplant taking place in 2005 in France.
As of December 2015, there have been a total of 31 face allotransplantations reported worldwide. In 2014, Smeets et published a systematic analysis of outcomes involving face allotransplantations. There were a total of 27 face transplantations that took place worldwide. Ten of the 27 face transplants were full face transplantations, with the remainder being partial face transplants. The literature did not report on any cases of graft loss, chronic rejection, or graft-versus-host disease. However, all face transplant individuals who were 1 year post-surgery reported experiencing 1 episode of an acute rejection following the procedure. Other common complications were related to drug toxicity from immunosuppressive therapy, leading to opportunistic infections, metabolic disorders, and increased incidence of malignancy. There have been 3 reported cases of malignancy to date. Three deaths occurred in the transplant recipients. One individual died 27 months after surgery due to lack of compliance with immunosuppressive therapy. A second death occurred in an early transplant French recipient who had multidrug-resistant infection and graft necrosis. A third individual died of recurrent cancer.
In regard to function, tactile sensitivity recovered at an average of 4.1 months post-surgery when nerve repair was performed or at an average of 7.3 months, without nerve repair. Temperature sensitivity recovered at an average of 4.3 months with nerve repair and at 12.5 months without nerve repair. Motor recovery began at an average of 7.8 months after surgery. The recovery of motor function started with contractions of single muscles, and complex movements appeared within the first year in a number of the recipients.
Long-term results are still forthcoming in most face allotransplantations. After 5 years of follow-up, the first face transplant recipient was able to fully open her mouth, smile, speak, chew, and swallow.
Another published study in 2015, by Fischer et al, reported on 29 face transplants performed through 2013. The study reported on the functional outcomes on five of those 29 face transplants before and after the face transplantation. Prior to surgery, all 5 individuals had compromised respiratory status, sensations, and facial expression. Following the surgery, they had considerable improvement in breathing post-surgery, speech improvement 3 to 9 months after surgery, as well as response to light touch and distinguishing between hot and cold. All 5 of the recipients being followed were capable of oral food intake, 3-29 days following surgery, with no restrictions from 3 to 12 months after surgery. However, all 5 individuals did develop opportunistic infections following the face transplantation.
SUMMARY
There are ongoing clinical trials involving composite tissue allotransplantation for face and hand/upper limbs. To date, the sparsity of evidence is based on small case series and systematic reviews of case studies worldwide. Although the studies on composite tissue allotransplantation reveal the surgery is technically feasible, the functional outcomes and data for improvement on quality of life are lacking. Composite tissue allotransplantation is associated with potential risks and benefits. Individuals who undergo face or hand transplantation must adhere to a lifelong regimen of immunosuppressive drugs. Risks of immunosuppression include acute and chronic rejection, opportunistic infection that may be life-threatening, and metabolic disorders such as diabetes, kidney damage, and lymphoma. There are also potential adverse impacts on quality of life, including the need to commit to the immunosuppression regimen. Therefore, the data has not proven whether the benefits outweigh the risk. The evidence is insufficient to determine the effects of the technology; composite tissue allotransplantation for face and hand(s) on health outcomes.
