Long-term survival following hematopoietic cell transplantation (HCT) is dependent on the eradication of primary disease and the rapid restoration of durable hematopoiesis and immune competence. Despite more precise HLA typing, novel cytoreductive regimens, and improved methods to detect and treat opportunistic pathogens, infection, with or without GVHD, remains the primary cause of transplant mortality in patients lacking an NLA-matched sibling. The purpose of this core is to provide a centralized program to monitor the effect of transplant regimen, donor and stem cell source (bone marrow, peripheral blood, cord blood), use of adoptive immunotherapy, and immunomodulatory growth factors (IL-7, KGF) on the kinetics of immunologic reconstitution, donor/host chimerism, and disease recurrence following allogeneic HCT. This core will longitudinally assess the quality and tempo of immunologic reconstitution following TCD related or unrelated PBSCT or unrelated double cord blood HCT by assessing the phenotype and/or function (proliferation, cytotoxicity, antibody production) of the recovering monuclear cell populations, including NK, T and B lymphocytes, monocytes, and dendritic cells. It will monitor the recovery of recent thymic emigrants, regulatory T cells, dendritic, and monocyte subpopulations by four color immunofluorence and presence of T cell receptor exicion circles (TREC). This core will be responsible for tetramer production used to analyze the reconstitution of circulating antigen-specific T cells following infusion of viral or WT1 specific cytotoxic T cells and will assess functional recovery of these antigen specific cells (intracellular cytokine production, cytotoxicity, proliferative capacity). It will monitor the chimeric status of recovering mononuclear cell populatons and assay for minimal residual disease by minisatellite PCR analysis and detection of WT1 transcripts, respectively. These studies will help gauge the effects of stem cell source (PBSC, BM, umbilical cord blood), donor selection (HLA-matched related, mis-matched related, or unrelated), use and method of T cell depletion, and immunomodulatory agents (interleukin-7, KGF, viral and/or tumor specific- CTLs) on the most common transplant related complications, namely relapse, regimen related toxicity, and infection. Lay abstract. Infection arid disease recurrence are significant causes of transplant failure. This core will evaluate the impact of transplant type, cytoreduction, and immunotherapy on these parameters.
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