A randomized trial comparing the combination of granulocyte-macrophage colony-stimulating factor plus granulocyte colony-stimulating factor versus granulocyte colony-stimulating factor for mobilization of dendritic cell subsets in hematopoietic progenitor cell products

• Published in: Biology of blood and marrow transplantation Vol. 10; no. 12; pp. 848 - 857
• Main Authors: Lonial, Sagar, Hicks, Michelle, Rosenthal, Hilary, Langston, Amelia, Redei, Istvan, Torre, Claire, Duenzl, Mary, Feinstein, Bonita, Cherry, Judith, Waller, Edmund K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2004
• Subjects: Adult; Aged; Blood Cell Count; Cohort Studies; Cytokine modulation; Dendritic cell subsets; Dendritic Cells - cytology; Dendritic Cells - drug effects; Female; Granulocyte Colony-Stimulating Factor - therapeutic use; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Hematopoietic Stem Cell Mobilization - adverse effects; Hematopoietic Stem Cell Mobilization - methods; Humans; Lymphoma - therapy; Male; Middle Aged; Multiple Myeloma - therapy; Recombinant Proteins; Stem cell transplantation; Stem Cell Transplantation - adverse effects; Stem Cell Transplantation - methods; Surveys and Questionnaires; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Cytokine modulation; Stem cell transplantation; Dendritic cell subsets
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2004.07.008

The ability of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration to increase the content of blood leucocytes and hematopoietic progenitor cells (HPCs) is well established, yet the effect of these cytokines on immune function is less well described. Recent data indicate that plasmacytoid dendritic cells (DC2) may inhibit cellular immune response. We hypothesized that administration of the combination of G-CSF and GM-CSF after chemotherapy would reduce the type 2, or plasmacytoid, DC2 content of the autologous blood HPC grafts compared with treatment with G-CSF alone. To test this hypothesis, 35 patients with lymphoma and myeloma were randomized to receive either G-CSF or the combination of G-CSF plus GM-CSF after chemotherapy, and blood HPC grafts were collected by apheresis. Cytokine-related adverse events between the 2 groups were similar. More than 2 × 10 6 CD34 + cells per kilogram were collected by apheresis in 14 of 18 subjects treated with G-CSF and in 16 of 17 subjects treated with GM-CSF plus G-CSF ( p = not significant). There were minor differences between the 2 groups with respect to the content of T cells and CD34 + cells in the apheresis products. However, grafts collected from recipients of the combination of GM-CSF plus G-CSF had significantly fewer DC2 cells and similar numbers of DC1 cells compared with recipients treated with G-CSF alone. A third cohort of patients received chemotherapy followed by the sequential administration of G-CSF and the addition of GM-CSF 6 days later. Grafts from these patients had a markedly reduced DC2 content compared with those from patients treated either with G-CSF alone or with the concomitant administration of both cytokines. These data, and recent data that cross-presentation of antigen by DC2 cells may induce antigen-specific tolerance among T cells, suggest that GM-CSF during mobilization of blood HPC grafts may be a clinically applicable strategy to enhance innate and acquired immunity after autologous and allogeneic HPC transplantation.