Dendritic Cell Reconstitution Following Autologous Stem Cell Transplant for Multiple Myeloma.

High dose therapy followed by autologous stem cell rescue for the treatment of multiple myeloma has been shown to be associated with improved outcome including increased complete response rates and survival. It is unclear what role, if any, autologous dendritic cell (DC) reconstitution patterns play in determining outcome. DC in peripheral blood (PB) can be divided into two subsets: DC1, which favor Th1 responses and DC2, which favor Th2 responses and in some cases appear to be immunosuppressive. In this companion study to a tandem stem cell transplant research protocol, PB DC subsets were studied prior to the administration of mobilizing chemotherapy (baseline), at the time of stem cell collection, on the day of transplant and at post transplant d. 15, 30, 60, and 90 following the first transplant. GM-CSF was used as part of the mobilization regimen as well as to enhance neutrophil recovery post-transplant. DC were identified as lineage (CD3/14/16/19) negative, HLA-DR⁺. Of these cells, DC1 were identified as CD11c⁺CD123⁻ or CD33^hiCD4^lo, and DC2 were identified as CD11c⁻CD123⁺ or CD33^lo/−CD4⁺. Sixteen patients have been enrolled and 11 are at least 90 d. post transplant #1. Median followup time is 12 months (range 7–25 months). 5 patients currently are in complete remission, 3 have had partial responses, 2 have stable disease, and 1 died of recurrent disease. In most cases, DC1 counts were higher than DC2 counts at all time points examined. At baseline, this was true for 77% of patients, indicating at baseline most patients maintain the higher DC1 numbers found in healthy humans. DC numbers increased in mobilized PB, and correlated well with the patients’ baseline counts. GM-CSF was more efficient at increasing DC2 than DC1, as has been reported for G-CSF. Post-transplant, DC recovery to at or near baseline levels occurred in most patients by d. 60. There was a trend for patients who are currently disease-free and those with partial responses to have a lower DC1:DC2 ratio (i.,e., DC2 reconstitution occurred more vigorously than DC1 reconstitution). The patient who died of progressive disease had the highest DC1 counts at several time points, and among the lowest DC2 counts leading to a consistently high DC1:DC2 ratio at 30, 60, and 90 days post-transplant. This finding suggests that in autologous transplant for multiple myeloma, proportionately increased numbers of DC2 are not associated with an increased risk of relapse, as was previously reported for allogeneic bone marrow transplant, but instead are associated with an improved likelihood of complete remission. Mobilization with a growth factor that favors the DC2 subset, such as GM-CSF, may promote the post-transplant production of a DC population that is able to assist in maintaining a complete response to high dose chemotherapy. If these trends are maintained upon final analysis of the patient population, additional means of selectively increasing DC2 numbers in this transplant setting would warrant further investigation.