Long-term Outcomes After Facial Allotransplantation: Systematic Review of the Literature

Abstract

Original Clinical Science-General Background. Facial vascularized composite allotransplantation (fVCA) represents a reconstructive approach that enables superior improvements in functional and esthetic restoration compared with conventional craniomaxillofacial reconstruction. Outcome reports of fVCA are usually limited to short-term follow-up or single-center experiences. We merge scientific literature on reported long-term outcome data to better define the risks and benefits of fVCA. Methods. We conducted a systematic review of PubMed/MEDLINE databases in accordance with PRISMA guidelines. English full-text articles providing data on at least 1 unique fVCA patient, with ≥3 years follow-up, were included. Results. The search yielded 1812 articles, of which 28 were ultimately included. We retrieved data on 23 fVCA patients with mean follow-up of 5.3 years. More than half of the patients showed improved quality of life, eating, speech, and motor and sensory function following fVCA. On average, the patients had 1 acute cell-mediated rejection and infectious episode per year. The incidence rates of acute rejection and infectious complications were high within first-year posttransplant but declined thereafter. Sixty-five percent of the patients developed at least 1 neoplastic or metabolic complication after transplantation. Chronic vascular rejection was confirmed in 2 patients, leading to allograft loss after 8 and 9 years. Two patient deaths occurred 3.5 and 10.5 years after transplant due to suicide and lung cancer, respectively. Conclusions. Allograft functionality and improvements in quality of life suggest a positive risk-benefit ratio for fVCA. Recurrent acute rejection episodes, chronic rejection, immunosuppression-related complications, and heterogeneity in outcome reporting present ongoing challenges in this field.

Clinical and preclinical tolerance protocols for vascularized composite allograft transplantation

“…The constant threat of acute and CR, along with a requirement of intense lifelong IS therapy with a long list of potential sequelae, significantly limits VCAs’ benefit and application [ 65 , 66 ]. Multiple VCA-related deaths have indeed been reported in patients receiving facial allotransplantation [ 67 ]. This presents a significant ethical concern regarding the use of VCAs.…”

Regulatory T Cells: Liquid and Living Precision Medicine for the Future of VCA

“…Specifically, the transplantation of facial VCAs (fVCAs) has shown promising short-and long-term functional and aesthetic outcomes. 1,7 However, one must be aware of the immunological hurdles associated with VCA because this type of transplant is composed of tissues with suspected varying immunogenic-ity‚ such as skin, mucosa, muscle, vasculature, and lymphatics (Figures 2 and 3). 91 We have yet to fully understand the pathophysiology of deep tissue rejection (eg, muscle, vasculature) because most mechanistic investigations on VCA rejection are done using skin samples, the tissue type easiest to biopsy.…”

“…3 Furthermore‚ the long-term survival of the allograft can be subject to acute and chronic graft rejection in solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA), such as face, hand, penile, or abdominal wall transplants. 1,[4][5][6][7][8][9][10] Given the higher rate of diagnosed acute rejection episodes in up to 85% of VCA recipients, the link between long-term allograft survival and rejection episodes could theoretically even be more pronounced in VCA. 11 One approach to optimizing this risk-benefit ratio is the development of therapies allowing for safe reduction of immunosuppression.…”

Tolerance Induction in Vascularized Composite Allotransplantation—A Brief Review of Preclinical Models

“…To date, about 150 vascularized composite allotransplants (VCAs) including over 40 face and 120 extremity transplantations, have been performed worldwide. Approximately 40 VCA programs across five continents have been established to date, and more VCA centers are anticipated to be established in the future ( 1 , 2 ).…”