Mixed chimerism: preclinical studies and clinical applications

Traditional approaches to allogeneic stem cell transplantation have relied on the use of toxic high-dose conditioning therapy to achieve allogeneic engraftment and control of underlying disease. Preclinical observations have shown that, for engraftment purposes, conditioning regimens can be reduced in intensity, resulting in reduced treatment toxicities. In preclinical canine studies, the use of potent pre- and postgrafting immunosuppression allowed for reduction in conditioning regimens and development of stable mixed chimerism. If these newer approaches using attenuated conditioning regimens can be successfully applied to human transplantation, an improved safety profile will allow potentially curative treatment of patients not currently offered such therapy. Mixed chimerism per se could prove curative of disease manifestation for various nonmalignant disturbances of the hematopoietic and immune systems. For patients with malignancy, infusion of additional donor lymphocytes may be needed to effectively treat underlying disease.