The incidence of post transplant complications, such as graft failure, disease recurrence, and infection, depend not only on host factors and the cytoreduction employed, but also on characteristics of the graft which impact on its ability to give rise to full and durable donor chimerism, hematopoesis, and reconstitution of the immune system. The biological significance of minor genetic disparities between donor and host detected by Class I and Class II DNA typing, or the abnormal immune studies documented in vitro in patients post transplant is suggested by the increased incidence of graft rejection, severe graft versus host disease, and fatal infectious complications, particularly in adults following unmodified, partially T cell depleted, or fully TCD unrelated marrow transplantation. Investigation of the mechanisms underlying resistance to engraftment, disease recurrence, and susceptibility to infection, and the clinical strategies designed to overcome them form the basis of this program project. It is therefore the aim of this core project to provide a centralized program to monitor the effect of stem cell source and its subsequent manipulation on the quality of the graft infused, donor/host chimerism, and immune reconstitution. The stem cell transplants will be analyzed for degree and quality of T-cell depletion, nucleated and CD34+ cell dose, and hematopoetic progenitor cell content. The regenerating marrow and circulating lymphoid cells will be assessed for lineage specific chimerism by ministatelite PCR analysis. The phenotype, antigen-specific and non-specific proliferation, cytotoxicty, and cytokine production of the circulating lymphoid populations will be longitudinally evaluated. These studies will provide an analysis to gauge the effects of stem cell source (marrow, peripheral blood, cord blood), degree of histoincompatibility, alternative methods of cytoreduction, T-cell depletion, graft rejection prophylaxis, and adoptive immunotherapy on engraftment, disease eradication, and the redeveloping immune system.
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