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 ASSH Hand Transplantation Policy, June 2013

The first case of hand transplantation was performed by French surgeons in September 1998.  Unfortunately, this unilateral transplantation resulted in re-amputation within several months, in large measure as a consequence of poor patient compliance.  Shortly after this case the first American hand transplant was performed in Louisville, Kentucky.  This individual’s transplanted hand has survived and functioned well.  However, despite this clinical success, there have been substantial complications related to immunosuppression in subsequent hand transplant recipients including avascular necrosis of both femoral heads, requiring hip arthroplasties.
 
Worldwide there have been close to 65 hand transplants documented, although it is possible that a greater number of undocumented cases may have been performed.  In addition to hand transplants, there has been transplantation done at a variety of proximal limb locations including above elbow levels and at the proximal forearm.  Partial hand transplantations have also been reported.  In addition to the upper extremity, vascularized composite allotransplants of the abdominal wall, larynx, the entire face and lower extremities have been reported.
 
For hand transplantation the variables that most affect outcome appear to be compliance both with an intensive program of hand therapy as well as with post-transplantation immunosuppressive therapy.  Careful patient selection is fundamental to meeting these critical therapeutic objectives.  As a result, in centers where hand transplantation is being performed, multidisciplinary teams that can fully assess candidates from not only a medical and surgical standpoint, but also from a psychosocial perspective, have proven to be essential.
 
The overall results from hand transplantation have, so far, been generally satisfactory.  Functional and cosmetic outcomes, particularly for bilateral amputees, have been similar to or better than hand replantation following traumatic amputation.  As is frequently the case with peripheral nerve injuries proximal to the wrist, intrinsic muscle function has not been restored to the transplanted hand in most instances.  As expected, and consistent with the experience with major limb replantations, the return of motor function with transplantation of limbs above the wrist is determined by the quality of re-innervation of the extrinsic flexors and extensors, and this has been more reliable than the reinnervation of the intrinsic muscles with hand transplantation.
 
One of the main concerns related to hand transplantation is the long term effects of lifelong immunosuppression.  However, it now appears clear that the level of immunosuppression required is equivalent to that used for kidney transplantation and the risks are approximately equal to those incurred by renal transplant recipients.  Newer concepts in immunosuppression are also evolving.  For example, a cellular based approach that uses donor bone marrow cell augmentation rather than a multiple drug regimen to prevent or truncate episodes of rejection has been used.  However, complications from chronic immunosuppression continue to be a concern.  Intimal hyperplasia leading to vascular compromise in the graft resulting in delayed thrombosis and transplant loss has been reported.  Major systemic problems such as fulminating sepsis and diabetes have also occurred.  Regardless of the nature of the immunosuppressive regimen, episodes of rejection of varying magnitude have been experienced by all patients who have undergone vascularized composite allotransplantation (VCA).
 
The number of cases that have been performed worldwide notwithstanding, hand transplantation is still considered an innovative intervention in most institutions, but several centers consider it to be standard of care for bilateral amputees.  There are several centers in the United States that have demonstrated a dedication to the further development of knowledge in this field and, as experience increases, the number of institutions capable of carrying out these procedures will grow.  Advances in solid organ transplantation, especially in the areas of tissue typing and refinement of immunosuppression protocols, have resulted in improved graft and patient survival.  It seems likely that these advances will also benefit patients who undergo hand transplantation, although it is clear that a composite of skin, muscle, bone, nerve and tendon, presents a set of challenges for the control of rejection that is somewhat more complex than that associated with a solid organ transplant.
Public perception of what can be achieved with VCA is also changing.  In some jurisdictions, organ procurement organizations have scripted documents specifically to request hand donation.  However, despite the advances made in the technical and biologic aspect of VCA, ethical concerns are still expressed by some.  The fundamental issue relates to the overall value of hand transplantation.  Solid organ transplantation is unequivocally a life saving intervention in patients requiring heart or liver.  VCA, including the hand, do not save life, and in fact may introduce a threat of decreased lifespan secondary to the complications of chronic immunosuppression.  Nonetheless, there is a potentially dramatically improvement in the quality of life that may ensue from hand transplantation and, as a result, the cost/benefit analysis becomes one of quality versus quantity.  Where this has been carefully studied in a hypothetical context using methods like the standard gamble, unaffected individuals have attributed a net benefit to the idea of undergoing hand transplantation.  In a real world setting, issues of appropriate patient expectation and the expectation of truly informed consent to undergo this kind of treatment remain issues that require further development.
 
At this time the American Society for Surgery of the Hand recognizes that hand transplantation represents an alternative to prosthetic fitting and rehabilitation. However, advances should continue to be made in the areas of patient selection, surgical technique and immunosuppression.  Additional challenges include the funding of patients for these procedures and for the lifelong immunosuppressive treatment.  This procedure may have substantial merit in properly selected recipients; however for the present it should be carried out only in centers with extensive experience in both hand surgery and solid organ transplantation.  It will be only in this type of setting that the combined expertise of hand surgeons and transplant physicians can be brought together to ensure the best results possible, while at the same time creating knowledge from gained experience.  No less important will be the efforts of those with the responsibility of defining meaningful methods of evaluating those outcomes.