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Page 2 of 17 Xu et al. Plast Aesthet Res 2022;9:33 https://dx.doi.org/10.20517/2347-9264.2021.116

Keywords: Vascularized composite allotransplantation (VCA), lower extremity, ethics, limb salvage, replantation

INTRODUCTION
Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a
functional unit, usually without the primary purpose of extending life. This practice is in contrast with solid
organ transplantation, which is often lifesaving in nature. Among the most widely practiced and publicized
forms of VCA is transplantation of the upper extremity, including the forearm and hand. VCA of the lower
extremity, conversely, is a frontier that has been only minimally explored but has potential value. The
number of individuals with loss of at least one lower limb in the United States was estimated at 1,027,000 in
[1]
2005 and projected to more than double by 2050 . This pool may be up to three times larger than that of
[1]
upper extremity amputees . Amongst these individuals, 43% would be interested in VCA of the lower
extremity . However, compared with upper extremity VCA, VCA of the lower extremity has a higher
[2]
ethical burden, as lower extremity prosthetics offer excellent function for amputees with substantial
potential for enhancing the quality of life of qualified patients .
[3,4]

Here, we discuss the ethical considerations surrounding VCA of the lower extremity - informed largely by
evidence for upper extremity transplantation - in its current state of practice as well as how new
advancements in immunosuppression and technology may change the conversation. We also compare VCA
with limb salvage and replantation in this context.

HISTORY OF VCA OF THE LOWER EXTREMITY
The first lower extremity transplantation occurred in 2006 between three-month-old ischiopagus twins, a
unique autologous situation for which the recipient did not necessitate immunosuppression . In 2011, the
[5-7]
first attempt at bilateral transfemoral transplantation in an adult patient was performed after the 20-year-old
recipient sustained traumatic above-knee amputations from a motor vehicle accident . Unfortunately, the
[8]
recipient developed brain lymphoma 15 months post-transplant and immunosuppression was ceased,
resulting in rejection and the removal of both limbs [9,10] . The third and fourth attempts occurred in 2012 as
part of the world’s first efforts at triple and quadruple extremity allotransplantation, respectively [11,12] . Both
recipients experienced rejection in the immediate postoperative period that required reamputation of the
allografts. The third recipient died within 5 months and the fourth recipient within 1 week of the procedure
due to complications [11,12] . Most recently, in 2018, a 32-year-old male underwent unilateral transfemoral
transplantation after an above-knee amputation one year prior. Only a six-month follow-up has been
published, at which point the recipient was partially weight-bearing with evidence of sensory and motor
[13]
function recovery . These five reports are the only known cases of VCA of the lower extremity, with none
taking place in the United States.

While the evidence for lower extremity transplantation is sparse, roughly 150 patients have received hand
transplantations since the first successful attempts in 1998 and 1999 [14,15] . Following successful early
outcomes, in 2002, the International Registry on Hand and Composite Tissue Transplantation (IRHCTT)
was established as a means of collecting and synthesizing outcomes data in a centralized manner. Over the
past decade, experimental immunosuppressive protocols have been adopted by medical centers nationwide
and internationally. In 2014, the U.S. Department of Health and Human Services’ Organ Procurement and
Transplantation Network (OPTN) Final Rule was modified to include limbs (both upper and lower
extremity), faces, and other VCAs under the definition of “organs” in order to supervise the processes for
identifying potential donors, requesting authorization, and safely and effectively allocating VCAs . At the
[16]
time of publication, 20 unique transplant programs for any type of VCA (e.g., limb, abdominal wall, face,