Research ArticleKidney transplant

Chimerism and Tolerance Without GVHD or Engraftment Syndrome in HLA-Mismatched Combined Kidney and Hematopoietic Stem Cell Transplantation

Science Translational Medicine  07 Mar 2012:
Vol. 4, Issue 124, pp. 124ra28
DOI: 10.1126/scitranslmed.3003509

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Teaching Tolerance

According to Greek mythology, the Chimera was a fire-breathing creature made of parts from different animals: the body of a lioness, a snake’s head at the end of the tail, and the head of the goat. Sightings of this fearsome beast portended any of a number of terrible disasters. In the context of organ transplantation, a “chimera” can indicate both desirable and disastrous outcomes. For example, hematopoietic chimerism, in which the immune cells in the graft recipient come from both the host and the donor, may promote graft tolerance, but may also cause graft-versus-host disease (GVHD), in which the donor immune cells attack the healthy tissue of the host. Leventhal et al. now report mixed chimerism and tolerance without the negative side effects of GVHD or engraftment syndrome in a phase 2 clinical trial of combined kidney and hematopoietic transplantation.

Leventhal et al. used a combination of mobilized cells enriched for hematopoietic stem cells and graft-facilitating cells—which are composed largely of plasmacytoid precursor dendritic cells—with nonmyeloablative conditioning in conjunction with kidney transplant from major histocompatibility complex–mismatched, nonrelated donors and recipients. Five of eight kidney transplant recipients exhibited durable chimerism and were weaned off immunosuppressive therapies by 1 year after transplantation, with no signs of GVHD or engraftment syndrome. If confirmed in larger patient cohorts, this approach to transplantation could free some patients from the difficulties associated with lifelong immunosuppression and add transplantation as a viable option for patients for whom no matched donors exist. As with the Chimera of legend, mixed chimerism may be a harbinger of things to come—albeit hopefully a brighter future for transplant patients.