Liver transplantation without immunosuppression: future perspectives.
ABSTRACT It has been hypothesized that a state of microchimerism in recipients of organ transplants may result in donor-specific tolerance to the graft. Numerous studies show that infusion of donor-derived bone marrow cells can, indeed, achieve systemic chimerism in the recipient and effectively prolong allograft survival. We have compared organ and patient survival in recipients of liver allografts alone (controls) or in combination with single or multiple infusions of donor bone marrow cells; recipients were infused either at day 0 (perioperatively) or at day 0 and 11 post-transplant. The incidence of rejection episodes and survival of the liver allograft were significantly reduced in recipients of two bone marrow infusions compared to controls; recipients of one infusion, conversely, experienced a higher number of rejection episodes when compared to controls, pointing to a possible sensitizing role of a single bone marrow infusion if administered perioperatively. Variables such as timing, number and composition of the bone marrow inocula still remain to be elucidated but may be of critical importance for the attainment of a state of donor-specific tolerance without the need for immunosuppressive therapy in recipients of organ allografts.
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ABSTRACT: A 2-year-old boy underwent liver transplantation for fulminant hepatic failure of unknown cause. Four months later the child developed severe aplastic anemia. Allogeneic bone marrow transplantation (BMT) was performed using marrow from his 14-month-old HLA-identical sister. Severe aplastic anemia recurred 2.5 months later. After reconditioning a second BMT was performed using the same donor. Tapering of immunosuppression 2 years after BMT led to biopsy-confirmed rejection of the liver. Therapy with high-dose corticosteroids and an increase in cyclosporine A medication readily reversed rejection and a low-dose immunosuppression reflected by cyclosporine trough levels less than 50 ng/ml has been maintained since. Eight years later the boy is in excellent health with both bone marrow and liver functioning perfectly. In summary, this case demonstrates that even recurrent severe aplastic anemia after OLT can be cured by BMT, and that a transplanted liver can tolerate a double conditioning regimen without problems. Tolerance towards the liver through BMT did not develop.Transplant International 02/2002; 15(1):39-44. · 3.16 Impact Factor