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 x 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.