Although vascularized composite allotransplantation (VCA) remains a controversial topic in upper limb amputations, hand transplantation remains an important restorative surgery that can currently be provided for upper limb amputations. Hand loss is a devastating event that affects nearly every activity of daily living and leaves patients with substantial disability.^1,2 The effect on a patient of losing both sensibility and prehension often results in despondency, and its adverse consequences cannot be overstated. Despite promising technologic advances in upper limb prostheses, the available literature still demonstrates high prosthesis rejection rates for upper limb amputations. These findings suggest that prostheses cannot replicate the complex prehensile and sensory functions of the native hand and arm in a reliably comfortable and useful form.^{3,4,5,6,7,8,9,10,11} Residual limb discomfort, prosthesis weight, and limited usefulness remain the most commonly cited reasons for the rejection of upper limb prosthetics.^3,12,13

Hand transplant pioneers surmised that prosthetic devices would never completely satisfy an individual with an upper limb amputation. Even if dexterity and prehensile function of the human hand could be restored, these would do little to restore highly coveted body image or hand sensibility. Rather, they postulated that these functions could be replaced only with “like” human tissue and full neural reintegration.¹⁴ The VCA field has grown from this desire to fully restore the functional and emotional aspects of the human hand (Figure 1).

The world’s first hand transplant, likely inspired by the solid organ transplantation community’s rapid growth, was performed in South America in 1964.^1,15,16 Unfortunately, because of relatively primitive immunosuppression techniques as well as a lack of basic science preparation, acute rejection predictably occurred, and the transplanted limb was amputated less than 1 month later.^12,17 This failure, or the realization that the hand surgery community had reached too far, too fast, resulted
in a long interval before the next hand transplant attempt in Lyon, France, in 1998.^12,18,19 Technically, this procedure succeeded; however, the technical success was unsustainable because the patient did not adapt psychologically to the new hand and discontinued immunosuppressive medications. The limb was eventually amputated because of chronic rejection and lack of function.¹ Dr. Warren Breidenbach performed the first truly successful hand transplant in the United States in 1999. The patient still has the transplanted hand currently—nearly 16 years later—with excellent function, even returning to work afterward.^12,13,20

Advances in solid organ transplantation made possible the early success in hand transplantation in the late 1990s. New medications, such as tacrolimus and mycophenolate mofetil, decreased the likelihood of rejection. Animal models of VCA have provided the basic and translational science evidence that successful allotransplantation without rejection is possible with these medications.^12,21,22,23 Since then, the VCA field has grown dramatically. Worldwide, estimates are that more than 130 hand transplants have been performed to date.

Primum non nocere—first do no harm—must be the paramount principle as the VCA field progresses. Cooney et al²⁴ echoed this sentiment in their 2002 American Society for Surgery of the Hand position statement, when they recommended “great caution and a measured approach to the patient requesting limb transplant.” This caution has, appropriately, slowed the growth of VCA compared with growth in solid organ transplantation. Because the patient considering hand transplantation is not faced with a life-or-death situation, hand transplantation is very different from most solid organ transplantations.²⁵ Developing widely accepted indications for subjecting a physiologically healthy person to the risks of lifelong immunosuppression remains the preeminent challenge for the allotransplantation community.²⁶

In 2009, Hollenbeck et al¹⁴ indicated that well-defined indications do not exist for hand or face transplants. Unfortunately, this statement currently remains relatively accurate, and the indications remain open to interpretation by individual VCA centers.^27,28 Having recognized the need for more refined indications for hand transplantation, the allotransplantation community founded the American Society for Reconstructive Transplantation in 2008, whose goal is to provide a platform for advancing composite tissue allotransplantation as relevant to reconstructive and transplant surgery. The society published guidelines for medical necessity determination for transplanting the hand and/or an upper limb. Despite this comprehensive and admirable attempt at defining indications, further refinement is necessary to ensure the safe advancement of the field.¹³

Hand allotransplantation represents a lifelong commitment by a surgeon, the patient, the patient’s family, and, ultimately, the healthcare system. Without the commitment of each entity, the true lifelong success of transplantation will not be realized. For this reason, screening for VCA is expensive and laborious, but vitally important. Every aspect of the life of the transplant candidate must be reviewed. Medical screening should include primary care, cardiology, infectious disease, and transplant medicine. In-depth evaluations of a patient’s behavior, social support, financial security, and psychiatric and psychological health are necessary and may ultimately disqualify a patient for transplant if possible risk factors that could lead to failure are identified. The outcome of a hand transplant is very much dependent on patient participation, cooperation, and compliance with hand therapy, medications, and follow-up screening appointments. Every preoperative screening is critical because these screenings may both predict patient compliance and identify other medical risk factors for failure. Literature specific to the VCA psychosocial screening is unfortunately limited, but Department of Defense-funded research is currently ongoing to hopefully add to this paucity of evidence.

The psychological assessment is likely the most critical component of transplant screening, and most patients
have been found to have at least one psychological disorder.²⁹ The success of a kidney, liver, or heart transplant depends only on a patient’s compliance with medications, but relatively high rates of medication noncompliance occur among patients who depend on the transplant(s) for life.^30,31 Among a combined heart and heart/lung transplant population, the only risk factor for graft loss between 6 and 12 months was being unmarried or not living in a stable relationship. The social support for an individual candidate must be identified, and a transplant should not occur if the surgeon is not comfortable with a patient’s support system.¹³ In one unique study by Kinsley et al,³² the authors queried hand transplant recipients from the International Registry on Hand and Composite Tissue Transplantation and suggested that anxiety, depression, posttraumatic stress disorder, participation in occupational therapy, expectations for posttransplant function, and family support are associated with postsurgical transplant status.