Bone marrow has been the standard source of hemopoietic cells for transplantation procedures and gene therapy applications for many years, but its presumed superiority over peripheral blood has recently come into question. The proposed research will, therefore, compare the relative contributions of CD34+ cells from these sources to initial engraftment and long-term hemopoietic reconstitution after autologous bone marrow transplantation in pediatric solid tumor patients (Specific Aims 1i and 1ii); further studies will assess the suitability of marrow versus peripheral blood for gene therapy by determining the proportions of transducible pluripotent stem cells in preparations from each source (Aim 1iii). Once an optimal source of progenitor cells has been found, it will be exploited to identify the subset(s) of CD34+ cells responsible for superior initial engraftment and long-term reconstitution (Aim 2). Finally, to ensure that improved hemopoietic recovery is not associated with inferior immune reconstitution, the subsets of CD34+ cells will be compared for the ability to restore adequate immunity in patients undergoing marrow ablative therapy. All evaluations will be based on a proven system of double genetic marking, in which blood or marrow cells are transduced ex vivo, infused into the patient and tracked for extended periods. Thus, it should be possible to obtain definitive answers as to which source of blood cells provides the best opportunity for stem cell transduction and repopulation in the recipient.
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