Outpatient allografting in hematologic malignancies and nonmalignant disorders--applying lessons learned in the canine model to humans

Cancer Treatment and Research
Michael Maris, Rainer Storb

Abstract

The novel allogeneic transplant approach outlined in this chapter proposes the dual concepts that currently used intensive cytoreductive conditioning programs can be successfully replaced by nonmyeloblative immunosuppression and that stem cell grafts create marrow space for engraftment through subclinical GVH reactions. Immunosuppression can be conceptually divided into two parts, one targeted exclusively towards host cells before transplantation, and the other aimed at both host and donor T lymphocytes after transplantation. The resultant effect is to either establish mutual graft-host tolerance as reflected by stable mixed donor-host chimerism or accomplish complete donor chimerism. Preclinical studies have demonstrated the feasibility of this new approach in the context of MHC-identical transplants in young canines. Early data from the dog model of severe hereditary hemolytic anemia suggest that mixed chimerism can partially correct the phenotypic expression of disease, but that complete chimerism will be necessary to halt the continued hemolytic process of the host type minority red blood cell population. In contrast, mixed chimerism would be expected to correct disease manifestations of other severe hereditary red blood ce...Continue Reading

Citations

Nov 25, 2005·Pediatric Transplantation·Morris KletzelReggie Duerst

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