Two Different Methods of Collecting Stem Cells For an Autologous Stem Cell Transplant in Treating Patients With Diffuse Large Cell Lymphoma

OBJECTIVES: Primary * Determine the therapeutic effect of instrument-driven lymphocyte enrichment of the autograft absolute lymphocyte count (A-ALC) compared to "standard autograft collection" as determined by progression-free survival post-transplantation. Secondary * Determine the profile of immune effector cells of the "lymphocyte enriched autograft" vs "standard autograft" and peripheral blood after autologous stem cell transplant (ASCT) and their impact on post- ASCT immunological reconstitution and clinical endpoints. * Perform quantitative and functional analysis of T, B, NK, and dendritic cells from the apheresis product and peripheral blood samples at multiple timepoints after transplantation. * Determine and compare the proportion of patients who are progression-free and alive at 1 and 2 years. * Determine the differences in overall survival between the two collection method arms. * Evaluate and characterize differences in transplantation outcomes (e.g., time to ALC engraftment, incidence of infection, and the CD34 count) between the two collection method arms. OUTLINE: Patients are stratified according to baseline International Prognostic Factor (≥ 2 factors vs \< 2 factors) and PET scan findings prior to transplantation (positive vs negative). Patients receive filgrastim (G-CSF) alone or G-CSF and sargramostim (GM-CSF) daily for stem cell mobilization. Once the peripheral CD34-positive cell count reaches ≥ 10/μL, patients undergo stem cell collection. Patients are then randomized to 1 of 2 treatment arms for standard autologous stem cell transplantation (ASCT). * Immunologic autograft engineering: Patients' stem cells are collected according to modified Amicus settings (i.e., MNC OFFSET = 0.0 and RBC = 7.0). Patients undergo ASCT IV on the day of apheresis (lymphocyte enriched autograft). * Standard autograft collection: Patients' stem cells are collected according to standard Amicus settings (i.e., MNC OFFSET = 1.5 and RBC OFFSET = 5.0). Patients undergo ASCT IV on the day of apheresis. Patients undergo blood sample collection periodically for immunological studies. Samples are analyzed for immunophenotyping of immune cell subsets via multicolor flow cytometry, immunoglobulin reconstitution, and functional T-cell immunity. After completion of study treatment, patients are followed at day 15 post ASCT and then at 3, 6, 9, and 12 months.