Nonmyeloablative hematopoietic stem cell transplantation: Transplantation for the 21(st) century

Conventional approaches to allogeneic stem cell transplantation have used t oxic high-dose conditioning therapy to achieve allogeneic engraftment and c ontrol of underlying disease. For engraftment purposes, preclinical studies and clinical observations have shown that conditioning regimens can be mar kedly reduced in intensity, resulting in reduced treatment toxicities. Prec linical canine studies demonstrated that the use of potent pre- and postgra fting immunosuppression allows for reduction in conditioning regimens while facilitating development of stable mixed chimerism. If attenuated conditio ning regimens can be successfully translated to human stem cell transplanta tion, an improved safety profile will allow potentially curative treatment to a more representative patient profile not currently offered such therapy . Mixed chimerism could prove curative of disease phenotype of various nonm alignant disturbances of the hematopoietic and immune systems. For patients with hematopoietic malignancy, spontaneous conversion to full donor hemato poeisis after stem cell transplant may prove curative by virtue of graft ve rsus host reactions directed against the malignancy, however infusion of ad ditional donor lymphocytes may be needed to treat persistent disease.