Long-term survival following hematopoietic stem cell transplantation (HSCT) is dependent not only on eradication of primary disease but on 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 HLA-matched sibling. The purpose of this core is to provide a centralized program to monitor the effect of transplant regimen, donor type and stem cell source on the quality of the graft infused, degree of donor/host chimerism, disease recurrence, and the kinetics of immunologic reconstitution. Stem cell grafts will be analyzed for degree and quality of T-cell depletion, nucleated and CD34+ cell dose, and progenitor cell content. The regenerating marrow and circulating lymphoid cells will be assessed for chimerism by minisatellite PCR analysis or FISH. The effect of adoptive immunotherapy for the treatment of EBV-LPD, relapse of CML or WT1 positive leukemia will be assessed by detection of EBV genome, BCR-ABL, and/or WT1 transcripts, respectively. The quality and tempo of immunologic reconstitution will be analyzed longitudinally by assessment of the phenotype and function (proliferation, cytotoxicity, antibody production) of the circulating lymphoid populations and correlated with recovery of serum insulin-like growth factor levels, T-cell receptor excision circle (TREC) positive cells, and infectious complications. These studies should help to gauge the effects of stem cell source (PBSC versus BM), donor selection (HLA-matched related, mis-matched related, or unrelated), use and/or method of T-cell depletion, intensity of cytoreduction (ablative or non-ablative), and immunomodulatory agents (recombinant growth hormone, interleukin-7, viral and/or tumor specific-CTLs) on the most common transplant related complications, namely relapse, regimen related toxicity, and infection.
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