Sandra Amaral1, Sudha Kilaru Kessler2, Todd J Levy3, William Gaetz4, Christine McAndrew5, Benjamin Chang6, Sonya Lopez7, Emily Braham7, Deborah Humpl3, Michelle Hsia3, Kelly A Ferry3, Xiaowei Xu8, David Elder8, Debra Lefkowitz9, Chris Feudtner10, Stephanie Thibaudeau11, Ines C Lin6, Stephen J Kovach6, Erin S Schwartz4, David Bozentka5, Robert Carrigan12, David Steinberg5, Suhail Kanchwala5, Dan A Zlotolow13, Scott Kozin13, Frances E Jensen14, Phillip R Bryant15, Abraham Shaked16, Matthew H Levine16, L Scott Levin17. 1. Division of Nephrology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: amarals@email.chop.edu. 2. Division of Neurology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA. 3. Department of Occupational Therapy, Center for Rehabilitation, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. 4. Department of Pediatrics; Division of Neuroradiology, Department of Radiology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 5. Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, USA. 6. Division of Plastic and Reconstructive Surgery, Department of Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 7. Division of Nephrology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 8. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. 9. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. 10. Department of Medical Ethics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. 11. Department of Plastic Surgery, McGill University, Montreal, QC, Canada. 12. Department of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. 13. Pediatric Hand and Upper Extremity, Shriners Hospital for Children, Philadelphia, PA, USA. 14. Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA. 15. Division of Rehabilitation Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 16. Department of Transplantation Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 17. Division of Plastic and Reconstructive Surgery, Department of Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, USA; Department of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Abstract
BACKGROUND: Although heterologous vascular composite allotransplantation has become a burgeoning treatment option for adult amputees, there have been no successful cases previously reported in children. Here, we describe the surgical, immunological, and neurorehabilitation details with functional outcomes 18 months after heterologous bilateral hand and forearm transplantation in an 8-year-old child with quadrimembral amputations and a previous kidney transplant. METHODS: 2 years of extensive preparation by medical and surgical teams preceded the hand-forearm transplantation of this child. The initial immunosuppressive protocol included thymoglobulin, tacrolimus, prednisone, and mycophenolate mofetil. In July, 2015, our vascularised composite allotransplantation team did the first bilateral hand and forearm transplantation in a child, an 8-year-old boy with previous living-related kidney transplantation. The surgery included four teams working simultaneously on the donor and recipient limbs, aided by customised cutting guides that aimed to reduce ischaemia time. Following an extended length of time in hospital, skin biopsies and close monitoring of renal function and drug concentrations occurred weekly for the first 3 months and were slowly tapered to monthly, and then quarterly. Skin biopsies were also done when tissue rejection was suspected. Paediatric-specific rehabilitation techniques were applied to promote patient engagement during rehabilitation. Progress was assessed by monthly sensory and motor function tests during routine clinic visits and with serial functional brain imaging studies, including structural brain MRI, magnetoencephalography and transcranial magnetic stimulation. FINDINGS: The surgery lasted 10 h and 40 min. Vascular revision of the ulnar artery was required a few hours postoperatively. There were no further immediate postsurgical complications. Rejection episodes occurred throughout the first year but were reversed. An increase in serum creatinine led to the addition of sirolimus at 3 months after transplantation with concomitant reduction in tacrolimus targets. Sensibility to light touch was present by 6 months after transplantation. Intrinsic hand muscle innervation was present by 7-10 months after transplantation. At 18 months, the child had exceeded his previous adapted abilities. As of 18 months after transplantation surgery he is able to write and feed, toilet, and dress himself more independently and efficiently than he could do before transplantation. He remains on four immunosuppressive medications and functional neuroimaging studies have shown motor and somatosensory cortical reorganisation. INTERPRETATION: Hand transplantation in a child can be surgically, medically, and functionally successful under carefully considered circumstances. Long-term data on the functional trajectory, neurological recovery, psychological sequelae, and the potential late effect of immunosuppression are still needed to support broader implementation of paediatric vascular composite allotransplantation. FUNDING: The Children's Hospital of Philadelphia.
BACKGROUND: Although heterologous vascular composite allotransplantation has become a burgeoning treatment option for adult amputees, there have been no successful cases previously reported in children. Here, we describe the surgical, immunological, and neurorehabilitation details with functional outcomes 18 months after heterologous bilateral hand and forearm transplantation in an 8-year-old child with quadrimembral amputations and a previous kidney transplant. METHODS: 2 years of extensive preparation by medical and surgical teams preceded the hand-forearm transplantation of this child. The initial immunosuppressive protocol included thymoglobulin, tacrolimus, prednisone, and mycophenolate mofetil. In July, 2015, our vascularised composite allotransplantation team did the first bilateral hand and forearm transplantation in a child, an 8-year-old boy with previous living-related kidney transplantation. The surgery included four teams working simultaneously on the donor and recipient limbs, aided by customised cutting guides that aimed to reduce ischaemia time. Following an extended length of time in hospital, skin biopsies and close monitoring of renal function and drug concentrations occurred weekly for the first 3 months and were slowly tapered to monthly, and then quarterly. Skin biopsies were also done when tissue rejection was suspected. Paediatric-specific rehabilitation techniques were applied to promote patient engagement during rehabilitation. Progress was assessed by monthly sensory and motor function tests during routine clinic visits and with serial functional brain imaging studies, including structural brain MRI, magnetoencephalography and transcranial magnetic stimulation. FINDINGS: The surgery lasted 10 h and 40 min. Vascular revision of the ulnar artery was required a few hours postoperatively. There were no further immediate postsurgical complications. Rejection episodes occurred throughout the first year but were reversed. An increase in serum creatinine led to the addition of sirolimus at 3 months after transplantation with concomitant reduction in tacrolimus targets. Sensibility to light touch was present by 6 months after transplantation. Intrinsic hand muscle innervation was present by 7-10 months after transplantation. At 18 months, the child had exceeded his previous adapted abilities. As of 18 months after transplantation surgery he is able to write and feed, toilet, and dress himself more independently and efficiently than he could do before transplantation. He remains on four immunosuppressive medications and functional neuroimaging studies have shown motor and somatosensory cortical reorganisation. INTERPRETATION: Hand transplantation in a child can be surgically, medically, and functionally successful under carefully considered circumstances. Long-term data on the functional trajectory, neurological recovery, psychological sequelae, and the potential late effect of immunosuppression are still needed to support broader implementation of paediatric vascular composite allotransplantation. FUNDING: The Children's Hospital of Philadelphia.
Authors: Sayf A Said; Carlos X Ordeñana; Majid Rezaei; Brian A Figueroa; Srinivasan Dasarathy; Henri Brunengraber; Antonio Rampazzo; Bahar Bassiri Gharb Journal: Mil Med Date: 2020-01-07 Impact factor: 1.437
Authors: William Gaetz; Sudha K Kessler; Tim P L Roberts; Jeffrey I Berman; Todd J Levy; Michelle Hsia; Deborah Humpl; Erin S Schwartz; Sandra Amaral; Ben Chang; Lawrence Scott Levin Journal: Ann Clin Transl Neurol Date: 2017-12-06 Impact factor: 4.511
Authors: Alexander Kaltenborn; Nicco Krezdorn; Sebastian Hoffmann; André Gutcke; Kirsten Haastert-Talini; Peter M Vogt; Axel Haverich; Bettina Wiegmann Journal: Mil Med Res Date: 2020-04-26