Lack of donor hyporesponsiveness and donor chimerism after clinical transplantation of the hand

BACKGROUND: Composite tissue allografts offer great potential in reconstructive surgery. However, the risks of immunosuppression and graft-versus-host disease (GVHD) after transplantation of vascularized bone in these grafts are significant. Transplantation of vascularized bone also may confer donor hematopoietic chimerism and, potentially, tolerance. We have followed two hand transplant recipients for more than 1 year to determine the level of chimerism and possible donor-specific tolerance, in addition to possible GVHD. METHODS: We performed kinetic studies on peripheral blood of two subjects after hand transplantation that included portions of the radius and ulna. We evaluated donor-specific reactivity, chimerism, and antibody production. RESULTS: Donor-specific tolerance did not develop clinically or in mixed lymphocyte reaction. The first subject recovered an excellent in vitro response to phytohemagglutinin, donor and third-party alloantigen, and by month 4 and at month 12 also recovered the ability to respond to Epstein-Barr virus. The second subject also demonstrated good in vitro proliferative responses, which were attenuated by immunosuppression. No phenotypic changes in mature hematopoietic lineages were detected by four-color flow cytometry other than those expected in response to immunosuppression. Donor chimerism was not detectable using four-color flow cytometry. Microchimerism (approximately 1:75,000 cells) was observed at the level of detection in some of the early posttransplantation specimens and was undetectable thereafter. CONCLUSIONS: In this particular transplantation and immunosuppressive regimen, the composite tissue allograft with vascularized bone marrow did not provide the immunologic benefit of tolerance induction nor cause GVHD.