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Upper Limb Reconstructive Transplantation in Military Recipients: Summary of World Experience

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Upper Limb Reconstructive Transplantation in Military Recipients: Summary of World Experience 6 Journal of the Royal Naval Medical Service 2018; 104(1) Upper limb reconstructive transplantation in military recipients: summary of world experience C A Fries, H L Stark, D Tuder, S Iyer, V S Gorantla, M R Davis, R F Rickard Abstract Lessons from conflict have contributed to military medical advances which have significantly improved the survivability of critically injured servicemen and women. However, survival following such severe combat polytrauma is often associated with devastating tissue loss and functional deficits that challenge conventional reconstruction. Despite recent advances, upper extremity prosthetic alternatives lack the fidelity to restore the complex intrinsic and sensory function of the human hand. Up- per Limb Reconstructive Transplantation, or Vascularised Composite Allotransplantation (VCA), is currently an experimental procedure offering superior anatomical and functional outcomes compared to prostheses. Military candidates for VCA usually enjoy high pre-morbid fitness, mental health resilience and support, and relatively rich provision of rehabilitation. However, co-morbidities of polytrauma, such as traumatic brain injury and post-traumatic stress dis- order, may have an impact on outcomes. Since 1998, over 120 upper limb transplants have been performed worldwide. Of these, six have been performed on service- men and women across three continents. The morbidity and mortality associated with the requirement for lifelong immunosup- pression, however, continues to skew the risk-benefit considerations of these promising procedures when compared to pros- theses. Thus, although the technical surgical feasibility of upper limb and other VCA such as face, abdominal wall, uterus and penis transplants has been established over the past decade, these procedures remain restricted to recipients fulfilling stringent inclusion criteria. We review the current state of VCA in military recipients, and summarise ongoing collaborative VCA research conducted by British and American military medical teams. Fries C A, Stark H L, Tuder D, et al. J R Nav Med Serv 2018;104(1):6–11 Introduction Vascularised composite allotransplantation (VCA) is the in- novative frontier of reconstructive surgery. Anatomical and From 2003 to 2012, the survivability of military wounds sus- functional restoration of even massive tissue loss can be ac- tained by British service personnel injured in Iraq and Afghan- complished with identical tissues from deceased donors. In istan improved year on year. In their elegant study Penn-Bar- the global experience of over 120 upper limb VCA, function- well et al. showed that the New Injury Severity Score (NISS) al, immunological and graft survival outcomes have ranged associated with a 50% chance of survival rose from 32 to 60 widely, from encouraging to poor. The primary risk-benefit during this period.1 The reason for success was multifactorial, consideration for these VCA is influenced strongly by the including incremental improvements in the military chain of morbidity and toxicity of multiple, high dose immunosup- care from the point of injury on the battlefield to definitive treat- pressive drugs required for graft maintenance. These risks ment at the Royal Centre for Defence Medicine in Birmingham. continue to limit the clinical application and benefits of these Improvements in techniques, tactics and procedures as well as life-enhancing but not life-saving procedures. At the time of equipment, notably in the universal provision of body armour this publication, six servicemen or women in the USA, In- and its evolution during the conflicts, also played a significant dia and Poland have undergone upper limb transplantation in role. Despite the best body armour, the limbs, head and neck, the context of blast injury. Four cases were bilateral and two and pelvis were exposed to devastating injury. The rates of am- unilateral. In this paper, we review the published literature putation and significant maxillofacial trauma are higher in this on these cases and summarise current military research and group of survivors compared to those of previous conflicts.2,3 future direction for VCA. Despite optimal reconstructive surgical approaches, rehabilita- tion therapy and modern prosthetics, functional outcomes are Military Cases highly unlikely to return to pre-injury levels. An imperative therefore exists for military medicine to advance reconstructive Table 1 summarises the military cases that have been per- surgery in tandem with advances in resuscitative care. formed to date. Original articles 7 Date Patient Indication Operation Centre Remarks Mar 2009 24 year old male Unilateral hand loss Unilateral hand VCA University of (blast injury) Pittsburgh Medical Center, USA Feb 2010 50 year old female Unilateral hand loss, Unilateral hand VCA Wilford Hall letter bomb Ambulatory Surgical Center San Antonio, TX, USA Jun 2010 31 year old male Bilateral hand loss, Bilateral hand VCA Trzebnica, Poland Female donor to training accident with male recipient explosive Dec 2012 26 year old male Bilateral hand loss, Bilateral hand VCA Johns Hopkins, Female donor to blast Baltimore, MD, USA male recipient May 2015 30 year old male Bilateral hand loss, Bilateral hand VCA Amrita Institute of blast, EOD Medical Sciences, Kochi, India Aug 2016 31 year old male Bilateral hand loss, Bilateral hand VCA Brigham and Women’s blast AFG Hospital, Boston, MA, USA Table 1: military cases of VCA performed to date. Case 1 Case 2 The first serviceman to receive a hand transplant in the USA Case two describes the first female hand allotransplantation was a 24-year-old Marine Corporal who had served two tours performed in the USA and the first to be conducted at a De- in Iraq. The patient had suffered a blast injury to the right hand fence establishment. The patient, a USAF master sergeant, in 2005 during military exercises at the Marine Corps base had sustained a traumatic left wrist disarticulation as the re- in Quantico, Virginia. He underwent informed consent after sult of a parcel bomb explosion within the continental Unit- exhaustive screening and comprehensive psychosocial assess- ed States. At the time of injury she was 50 years old, left ment. The donor was matched for limb size, skin colour, tone hand dominant and otherwise fit and well. She had subse- and gender. He received alemtuzumab induction with methyl- quently undergone numerous revision surgeries and multiple prednisolone. Transplantation was performed in March 2009 prosthetic trials without a satisfactory outcome. In February and tacrolimus monotherapy was commenced. The regimen 2010, after extensive medical and psychological screening, also included a novel cell-based immunomodulatory protocol, she underwent transplantation at the Wilford Hall Ambulato- the Pittsburgh protocol, that incorporates donor bone marrow ry Surgical Centre, San Antonio, USA. The donor hand was a (BM) infusion.4 Cryopreserved whole donor BM from nine skin colour-matched, CMV positive, deceased female donor. vertebral bodies was infused on day 14. The patient was mon- The procedure took 9.5 hours with an ischaemia time of 3.5 itored for clinical, functional and immunological outcomes hours. Following induction immunotherapy with thymoglob- with routine and specialised assays. The degree of motor and ulin and solumedrol, she was managed with a maintenance sensory return correlated with time after transplantation and regimen of tacrolimus, prednisolone and mycophenolate level of amputation. Immunomonitoring revealed transient mofetil. In the six years of follow up to date she has been moderate donor-specific antibodies, adequate immunocom- successfully treated for 11 episodes of acute rejection. In ad- petence and no immunological chimerism. High-resolution dition, she has suffered three episodes of CMV re-activation ultrasound demonstrated patent vessels with no luminal nar- and two episodes of acute kidney injury. Functionally, she rowing or occlusion. Side effects were few, with no system- now enjoys two-point discrimination in all fingers of 11mm, ic infectious or other serious complications. The patient was and is sensitive to hot and cold stimuli. She has developed satisfied with transplant-related quality of life outcomes and fixed flexion deformities of the PIPJ (45 degrees index and gained significant independence with personal and vocation- middle, 90 degrees ring and little finger) and has MCPJ range al abilities. However, at year two, he became non-compliant of motion of 0-90 degrees. Her pre-operative DASH score with medication and physician recommendations. He suffered was 37.5, post-operatively improving to 17.5. The patient is multiple episodes of recurrent steroid and antibody-resistant very happy with her outcome and has returned to work and rejection and eventually chronic rejection necessitated the am- horseback riding. She has required one additional revision putation of the allograft three years after transplantation. procedure. 8 Journal of the Royal Naval Medical Service 2018; 104(1) Case 3 Case 6 Case 3 was 31 at the time of his injury. He was a Polish Special Case 6 was a US Marine Sergeant, injured by an improvised Forces soldier and was injured in a training accident, saving a explosive device whilst serving in Afghanistan. He was 25 at young recruit from a bomb that then exploded in his hands. He the time of injury in 2010 and suffered quadruple limb loss. lost his left hand and the thumb and two fingers from his right. He underwent bilateral hand transplantation six years later, in He underwent bilateral hand transplantation three years later Baltimore, USA. The operation took 14 hours. At present there in Trzebnica, Poland. The operation took 17 hours. At present are no published follow up data (see Figure 2). there is no information published on his ongoing progress. Discussion Case 4 The complex intrinsic motor and sensory function of the hu- Case 4 was a US Army Sergeant and the first US soldier to sur- man hand is unique and fundamental to our interaction with vive quadruple traumatic limb loss. In 2008, at the age of 22, our environment. A review of all Royal Naval Service person- he was injured by a roadside bomb in Iraq.
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