progenitor cell grafts compared with administration of G-CSF alone after chemotherapy (Lonial et al 2004). They random- ized 35 patients with lymphoma and multiple myeloma to receive either G-CSF or the combination of G-CSF plus GM-CSF after chemotherapy. Blood hematopoietic progeni- tor cell grafts were collected by large volume apheresis. They found a similar incidence of cytokine-related adverse events, and similar numbers of stem cells mobilized between the 2 treatment groups. There were minor differences with respect to the content of T cells in the apheresis products. However, grafts mobilized with the combination of GM-CSF plus G-CSF had signiﬁcantly fewer DC2 and similar numbers of DC1 compared with grafts mobilized with G-CSF alone. A third cohort of patients received G-CSF and the sequential administration of GM-CSF 6 days later. Grafts from these patients had a markedly decreased DC2 content compared with grafts mobilized from patients treated with G-CSF alone or with the simultaneous administration of both cytokines. This preliminary trial formed the foundation for a randomized clinical trial where normal volunteer donors were randomized to receive either G-CSF or G-CSF plus GM-CSF in order to evaluate the impact of these cytokines on DC content, T-cell polarization, and immune function after allogeneic transplan- tation. Fifty patients were enrolled in the trial with 25 in the GM+G-CSF and 25 in the G-CSF alone arm. All patients were successfully mobilized. Among donors mobilized with G-CSF alone, the mean number of collections was 1.48 compared with 1.08 in the group receiving the combination of GM+G-CSF (p = 0.01). There was a trend toward a higher total cell dose in the G-CSF arm (p = 0.09). Two of the 25 donors in the G/GM group required more than 1 apheresis, and 8 of 25 donors in the G-CSF alone group required more than 1 collection to achieve an adequate number of CD34+ cells. Analysis of the T-cell and T-cell subset data revealed that in the group receiving G-CSF alone, there was a signiﬁ- cantly higher percent and total T-cell, CD4+ and CD8+ cell content of the grafts when compared with the group receiving the GM+G-CSF combination. Among dendritic cell subsets in the grafts, there was a signiﬁcantly lower percentage and fewer absolute numbers of DC2, as well as a lower delivered DC2 dose/kg for the group randomized to receive GM-CSF plus G-CSF compared with the group randomized to receive G-CSF alone (p 0.001). There was no signiﬁcant difference in the DC1 content or the content of CD34+ cells between the 2 treatment arms. Proliferation of the graft in response to T and B-cell mitogens was measured on the graft itself. Cells were exposed to mitogens or control for 72 hours, and then thymidine incorporation was measured. So far, there Biologics:Targets & Therapy 2008:2(1) Clinical uses of GM-CSF are available data on mitogen stimulation for 32 patients, showing a trend toward more IL-12 secretion for G+GM-CSF mobilized grafts, and more IL-2 secretion for G-CSF mobi- lized grafts. There have been no differences in the incidence of GvHD, relapse or survival between the 2 cytokine arms to date (Lonial et al 2004; Lonial et al 2006). These data, and data indicating that cross-presentation of antigen by DC2 may induce antigen-speciﬁc tolerance by T cells, suggest that the addition of GM-CSF to regimens during mobilization of peripheral blood progenitor cell grafts may be a clinically applicable strategy to enhance innate and acquired immunity after peripheral blood progenitor cell transplantation (Kuwana et al 2001; Gilliet and Liu 2002). Larger clinical trials are needed to determine the exact consequences of altering the DC1 and DC2 content of peripheral blood hematopoietic progenitor cell grafts. Those effects may include: incidence of acute and chronic GVHD, engraftment, graft rejection, graft versus leukemia effect and response to infection. Role of GM-CSF in post transplant immune reconstitution Recent data on the differential effects of GM-CSF and G-CSF on the DC subsets in the graft, has inspired clinical studies to investigate whether the administration of these cytokines following autologous hematopoietic stem cell transplanta- tion may inﬂuence the post-transplant reconstitution of cellular immunity. Fattorossi and colleagues conducted a randomized, prospective clinical trial to test for differences in immune recovery among 39 patients with ovarian and breast cancer who received either G-CSF or GM-CSF after high dose myeloablative chemotherapy and autologous transplantation. At day 12, GM-CSF was more efﬁcient at up-regulating membrane molecules on phagocytic cells important for antibody-dependent cytotoxicity and for the uptake of immune complexes compared to treatment with G-CSF; and at day 80, a signiﬁcantly higher proportion of mitogen-stimulated T cells from GM-CSF-treated patients expressed interleukin-2 receptor, and a higher proportion of these T cells were actively proliferating (Fattorossi et al 2001) . Recently, Gazitt and colleagues showed that among 29 non-Hodgkin’s lymphoma (NHL) patients receiving cyclophosphamide plus GM-CSF, G-CSF or GM-CSF fol- lowed by G-CSF for stem cell collection, patients mobilized with the GM-CSF containing regimens mobilized higher numbers of DC, and had a higher probability of survival compared to patients receiving G-CSF alone (median of 55 months versus 15 months; p = 0.02). Of note, there was no 17