ORIGINAL ARTICLE Outcomes After Bilateral Hand Allotransplantation A Risk/Benefit Ratio Analysis Palmina Petruzzo, MD, ∗ † Aram Gazarian, MD, ∗ ‡ Jean Kanitakis, MD,§ Helene Parmentier, BSc,¶ Vincent Guigal, MD,‡ Michel Guillot, MD,‖ Christophe Vial, MD, ∗∗ Jean Michel Dubernard, MD, ∗ Emmanuel Morelon, MD, PhD, ∗ †† and Lionel Badet, MD, PhD ∗ †† Background: The clinic era of composite tissue allotransplantation was inau- gurated by hand allotransplantation in 1998, giving rise to many controversies and scepticism because of the lifelong immunosuppression, the unclear risk- benefit ratio, and the uncertain long-term functional results of the procedure. The aim of this study was to evaluate the outcomes and the risk/benefit balance in bilateral hand allotransplantation. Methods: The study included 5 cases of bilateral hand allotransplantation performed in a single center, with a follow-up ranging from 3 to 13 years. The recipients (4 men, 1 woman) were young. The level of amputation was distal in all cases except for 2 patients amputated at the midforearm level. All the recipients initially received the same immunosuppressive treatment that included tacrolimus, mycophenolate mofetil, prednisone, and, for induction, antithymocyte globulins. Results: Patient and graft survival was 100%. All recipients showed adequate sensorimotor recovery (protective and tactile sensitivity and partial recovery of intrinsic muscles), they were able to perform the majority of activities of daily living, and had a normal social life. Most complications occurred in the first posttransplant year and were successfully managed. All recipients experienced at least 1 episode of acute rejection, which was easily reversed by increasing oral steroid dose or by intravenous steroids, except for patient 3, who presented 6 episodes of acute rejection, the latest 2 treated with Campath-1H. Conclusions: Although bilateral hand transplantation may be a satisfactory treatment option for amputees, a careful selection of candidates and a rigorous evaluation of recipients after transplantation are imperative. Keywords: bilateral hand allotransplantation, complications, functional recovery, outcomes, patient and graft survival (Ann Surg 2015;261:213–220) T he clinic era of composite tissue allotransplantation or vascular- ized composite allotransplantation was inaugurated by hand al- lotransplantation in 1998, giving rise to controversies and scepticism because of an unclear risk-benefit ratio concerning the risks of life- long immunosuppression and the uncertainty of long-term functional results of the procedure. The first hand allotransplantation showed the From the ∗ Department of Transplantation, Hˆ opital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; †Department of Surgery, University of Cagliari, Cagliari, Italy; ‡Chirurgie de la Main et du Membre Sup´ erieur, Polyclinique Orthop´ edique de Lyon, Lyon, France; §Department of Dermatology, Edouard Herriot Hospital, Lyon, France; ¶Institut des Sciences et Techniques de la R´ eadaptation, Claude Bernard Lyon I University, Lyon, France; ‖Rehabilitation Centre “Romans Ferrari,” Miribel, France; ∗∗ Groupe Hospitalier Est, Hˆ opital neurologique, Centre de R´ ef´ erence en Pathologie Neuromusculaire Rhˆ one- Alpes, Lyon, France; and ††Universit´ e de Lyon, Lyon, France. Disclosure: The authors declare no conflicts of interest. Reprints: Palmina Petruzzo, MD, Service d’ Urologie et Chirurgie de la Trans- plantation (Pavillon V), Hˆ opital Edouard Herriot, 5, Place d’Arsonval, 69437 Lyon Cedex 03, France. E-mail: petruzzo@medicina.unica.it and palmina.petruzzo@chu-lyon. Copyright C  2014 by Lippincott Williams & Wilkins ISSN: 0003-4932/14/26101-0213 DOI: 10.1097/SLA.0000000000000627 feasibility of the surgical technique, the efficacy of the immunosup- pressive protocol, the limited adverse events, and the importance of patient compliance to the immunosuppressive therapy and the reha- bilitation program. 1 On the basis of these results, hand allotransplan- tation programs were launched in the United States, China, Austria, Italy, Spain, Belgium, Poland, Mexico, and Australia; they resulted in motor and sensory functional recovery and a very high rate of graft survival at 1 year. 2–7 In 2000, a prospective study on bilateral hand transplantation was approved in France by the “Comit´ e de Protection des Personnes Participant ` a la Recherche Biom´ edicale,” although this procedure was accepted as “ethical” treatment of bilateral hand amputees several years later (North American surgeons’ survey, 2009). 8 At that time, no set of indications for hand allotransplantation existed. Our team decided transplantation for only young, otherwise healthy bilateral amputees who had used myoelectric prostheses with poor satisfaction. When this study started 13 years ago, our primary goals were to evaluate the efficacy and safety of the immunosuppres- sive protocol and the possibility of a satisfactory functional recovery. We report herein the results of this cohort study, including 5 bilateral hand allotransplantations, with a follow-up period ranging from 3 to 13 years to evaluate the risk-benefit ratio over the years. METHODS Study Design and Evaluation Procedures This study included 5 patients with bilateral upper extrem- ity amputation (hand and/or forearm) who underwent bilateral al- lotransplantation in a single center. Inclusion criteria were bilateral hand amputation for at least 6 months and age ranging from 18 to 40 years. As planned in the study design, medical and psychological evaluations were carefully performed in all potential recipients be- fore transplantation. In addition, specific and functional tests, such as angiography, electromyography (EMG), and magnetic resonance imaging (MRI) of the stumps, were performed (Table 1). All patients signed an informed consent to proceed with bilat- eral hand allotransplantation after an exhaustive presentation of the expected/foreseeable risks and benefits associated with this proce- dure. After transplantation, the general condition and functional results of the patients were evaluated at every annual follow-up (Table 1). Macroscopic graft examination and 4-mm punch skin biopsies were performed at regular time points postgraft, includ- ing 1, 3, 6, and 12 months during the first year; thereafter, every 6 months in the following 2 years, then at every annual follow-up and whenever a rejection was clinically suspected. The specimens for histological examination were formalin-fixed and paraffin-embedded; 5-micrometer-thick sections were stained with hematoxylin-eosin and examined for the presence of pathological changes suggestive of re- jection. Acute rejection (AR) severity was graded on the basis of the Banff 2007 score. 9 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Annals of Surgery  Volume 261, Number 1, January 2015 www.annalsofsurgery.com | 213