Organ Transplant Rejection Eliminated by Chimerism

A new study has reported that five organ-transplant recipients have remained healthy for up to five years without anti-rejection drugs, thanks to chimerism.

Researchers at Massachusetts General Hospital (Boston, USA) treated five patients with end-stage renal disease that received combined bone marrow and kidney transplants from human lymphocyte antigen (HLA) single-haplotype mismatched living related donors; all patients underwent a nonmyeloablative preparative regimen that included cyclophosphamide, an anti-CD2 monoclonal antibody (MoAb) drug (MEDI507), cyclosporine A, and thymic irradiation. The last two patients also received rituximab to deplete B cells. The patients then received kidney transplants and intravenous infusions of bone marrow from the HLA mismatched parents or siblings. Oral cyclosporine A at 8-12 mg daily began with transplant but was tapered and then discontinued over several months.

After transplant, both donor- and native-type leukocytes were found in the patients' blood; but by day 21, this mixed chimerism had disappeared. All the patients showed capillary leak syndrome (a sign of rejection), and one patient developed acute humoral rejection with irreversible loss of renal function. The four other patients were treated with corticosteroids and had cyclosporine withdrawn on schedule, with rejection symptoms eventually disappearing and kidney function remaining normal. In all four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The study was published in the January 24, 2008, edition of The New England Journal of medicine (NEJM).

"Stable graft function after planned, complete withdrawal of immunosuppressive drugs is feasible in recipients of HLA-mismatched grafts,” concluded lead author David Sachs, M.D., and colleagues.

Chimerism is an extremely rare disorder that mixes the chromosomal population in a single organism. In these cases, chimerism may manifest as the presence of two sets of DNA, or organs that do not match the DNA of the rest of the organism. Chimerism tends to occur very early in the embryonic development, and is often the result of two non-identical twin embryos merging together instead of growing on their own.


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