Mixed chimerism in SCT: conflict or peaceful coexistence?

Stem cell transplants that follow both myeloablative and non-myeloablative conditioning regimens can result in states of mixed chimerism, which can be stable over time. With widespread availability of Y chromosome FISH in sex-mismatched transplantation and DNA-based methodologies for analysis of chimerism in other donor-recipient pairs, further insights have been gained regarding the implications of the mixed chimeric state. In transplants performed for inherited and acquired marrow failure disorders, disease status can be improved with only 10-20% donor cells, and it appears that stable mixed chimerism at that level is an acceptable outcome often leading to a state of tolerance, but an increasing level of recipient cells often precedes graft rejection. In transplants performed for malignant conditions, increasing levels of mixed chimerism may indicate disease relapse, but some cases with stable levels of mixed chimerism have been compatible with prolonged remission states. Understanding when mixed chimerism is an indication of secondary graft failure or impending graft rejection vs a state of tolerance and ongoing propensity for the establishment of a graft-vs-tumor effect is often difficult with currently available technologies and immunologic assays. The ability to understand the implication of mixed chimerism of multiple cell lineages and of varied lymphocyte subsets will remain important areas for future research to best harness the immunologic and other therapeutic benefits of allogeneic transplantation.