The world's first double hand transplant in a child has been successful under carefully considered circumstances, according to a study in The Lancet.
The study presents the first medical report of the surgery and 18 months of follow-up. The recipient of the transplant was Zion Harvey, an 8-year-old boy based in the US, who is now able to write, and feed and dress himself independently following months of occupational therapy and psychological support. However, during this time he also faced setbacks, including treatment of numerous rejections of the hands and extensive rehabilitation to help him learn to use his hands.
"Our study shows that hand transplant surgery is possible when carefully managed and supported by a team of surgeons, transplant specialists, occupational therapists, rehabilitation teams, social workers and psychologists," says Dr Sandra Amaral, Children's Hospital of Philadelphia. "18 months after the surgery, the child is more independent and able to complete day-to-day activities. He continues to improve as he undergoes daily therapy to increase his hand function, and psychosocial support to help deal with the ongoing demands of his surgery."
Previously, this type of transplant had been used for single limbs between identical twins and in adults. In another case involving a teenager who received a donor limb, there were severe complications and the patient died soon after surgery.
The first double hand transplant surgery in a child took place at Children's Hospital of Philadelphia in collaboration with Penn Medicine. The boy was chosen for the surgery as he was already receiving immunosuppression for a kidney transplant, caused by a sepsis infection that also resulted in the earlier amputation of his hands and feet at the age of two.
Before the double hand transplant, he had limited ability to dress, feed and wash himself through adapted processes, using his residual limbs or specialist equipment. His mother's hopes for the surgery were for him to be able to dress, brush his teeth, and cut food independently, and the boy wanted to be able to climb monkey bars and grip a baseball bat.
The surgery took place in July 2015, when suitable donor organs became available from a deceased patient, and involved four medical teams working simultaneously on the donor hands and the child.
Six days after the transplant, the boy began daily occupational therapy, including video games and exercises using finger lights and puppets, as well as daily tasks like writing and using a knife and fork. He and his mother also met regularly with a psychologist and a social worker to help the boy cope with the transplant, and plan for his re-integration at school.
Within days of the surgery, the boy was able to move his fingers using the ligaments from his residual limbs. Regrowth of the nerves meant that he could move the transplanted hand muscles and feel touch within around six months, when he also became able to feed himself and grasp a pen to write. By eight months, he could use scissors and crayons, and within a year of the surgery, he could swing a baseball bat using both hands.
Functional brain imaging has revealed that the boy's brain has developed pathways for control of hand movement, and for carrying touch sensation signals from the hand back to the brain. However, since his surgery, he has undergone eight rejections of the hands, including serious episodes during the fourth and seventh months of his transplant. All of these were reversed with immunosuppression drugs without impacting the function of the child's hands. He remains on four immunosuppression drugs, including a steroid which can impact growth and bone health. The researchers plan to reduce the use of the boy's immunosuppression drugs when possible.
He has faced some minor infections and some impairment to his transplanted kidney as a result of the increased immunosuppression. While his function now surpasses what he was able to do before his transplant, he also faced a six-month period of reduced abilities immediately after the surgery. "While functional outcomes are positive and the boy is benefitting from his transplant, this surgery has been very demanding for this child and his family." adds Amaral.
The researchers explain that caution must be taken when assessing the benefits and harms of a hand transplant. Given the need for ongoing immunosuppression, the decision should be considered carefully for children who are not already exposed to immunosuppressive medications because of their associated risks such as diabetes, cancer and infections.
Lead surgeon, Dr L Scott Levin, chair of the department of orthopaedic surgery in the Perelman School of Medicine at the University of Pennsylvania, and surgical director of the Hand Transplantation Programme at Children's Hospital of Philadelphia, adds: "We believe that this hallmark vascularised composite allotransplantation case is repeating the evolution of solid organ transplant – moving this type of transplant from adults to children."
The researchers note that more data are needed to help improve this surgery in children, and that long-term follow-up will be needed to help inform others who may undergo the surgery in the future.
Summary
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.
Authors
Sandra Amaral, Sudha Kilaru Kessler, Todd J Levy, William Gaetz, Christine McAndrew, Benjamin Chang, Sonya Lopez, Emily Braham, Deborah Humpl, Michelle Hsia, Kelly A Ferry, Xiaowei Xu, David Elder, Debra Lefkowitz, Chris Feudtner, Stephanie Thibaudeau, Ines C Lin, Stephen J Kovach, Erin S Schwartz, David Bozentka, Robert Carrigan, David Steinberg, Suhail Kanchwala, Dan A Zlotolow, Scott Kozin, Frances E Jensen, Phillip R Bryant, Abraham Shaked, Matthew H Levine, L Scott Levin
[link url="https://www.sciencedaily.com/releases/2017/07/170719090127.htm"]The Lancet material[/link]
[link url="http://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(17)30012-3/fulltext?elsca1=tlpr"]The Lancet Child & Adolescent Health article summary[/link]