Hematopoietic cell transplantation could have wide clinical application in the treatment of hematological disorders, including blood dyscrasias and malignancy. Both the lack of suitable HLA-matched donors and the severe complications of GvHD have hampered use of this treatment modality. Previous studies in the lab of Dr. Sachs have established mixed chimerism and tolerance across defined MHC barriers in miniature swine through the use of cytokine mobilized peripheral blood mononuclear cells (CM-PBMCs). Isolated clinical reports have shown successful establishment of full chimerism in humans through HLA-mismatched PBSC transplantation. As this model is further extended to patients, pre- clinical data will become increasingly important in reducing clinical trial morbidity and mortality. Our goals are to evaluate the effect of delayed leukocyte infusion on chimerism and GvHD in mixed chimera animals. Ultimately we wish to establish complete donor hematopoietic chimerism while avoiding GvHD as a non-toxic approach to treatment of hematological dyscrasia and malignancy.
