Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established curative approach for a variety of malignant and nonmalignant hematologic disorders. Disease relapse, graft versus host disease (GVHD), infection, and regimen related toxicity remain the primary causes of transplant failure. The tempo and quality of hematopoietic engraftment and immune reconstitution significantly influence post-HSCT morbidity and mortality. Adult recipients of an allo-HSCT experience deficiencies in their B and T cell reconstitution, which can persist for over a year, and are associated with an Increased risk of infection, relapse, and secondary malignancies. Delayed reconstitution of CD4 T cells, associated with advanced patient age, HLA disparity, and method of prevention of GVHD and graft rejection, correlates with an increased risk of fatal opportunistic infections. Despite the increased use of molecular typing of HLA alleles for more stringent matching of patient and unrelated donors, and intensified regimens to prevent and treat invasive viral, fungal, and parasitic infections, opportunistic infections represent the primary cause of death in most unrelated transplant series, regardless of the stem cell source (bone marrow, peripheral blood, or cord blood), and irrespective ofthe use of T cell depletion. The clinical trials and research projects outlined in this grant are designed to test transplant approaches, biologicals and cell therapies to accelerate full functional recovery of the hematopoietic and immune systems and provide immune T-cells to eradicate viral infections and enhance resistance to leukemia in recipients of allo-HSCT. The purpose of Core A is to define hematopoietic cell grafts and adoptively transferred T-cells and their function prior to and following HSCT. Core A will characterize allografts and monitor the effects of stem cell source, donor type, use of T cell depletion, immunomodulatory agents, such as KGF or androgen blockade, and/ or adoptive immunotherapy, as well as development of GVHD on the kinetics and quality of immune reconstitution, donor chimerism, and minimal residual disease. Core A will also centralize specimen procurement and provide a centralized storage repository.
Over the last 20 years, this core facility has been responsible for performing phenotype, function, detection of minimal residual disease, and lineage specific chimerism in patients undergoing allo-HSCT on clinical trials at MSKCC. A detailed analysis of stem cell grafts and adoptively transferred T cells as well as immune monitoring in recipients of these cellular products is critical to our understanding of how these interventions can decrease morbidity and mortality and improve outcomes
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