Recovery of Lymphocyte and Dendritic Cell Subsets Following Reduced Intensity Allogeneic Bone Marrow Transplantation

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Abstract
Approaches using reduced conditioning regimens have been developed to obtain minimal procedure-related toxicity. Such novel therapeutic options are being explored with good preliminary results concerning feasibility and engraftment. However, many aspects remain under-evaluated and few data are available about immune and dendritic cell (DC) reconstitution after these highly immunosuppressive regimens. We present here our data in 20 patients receiving allogeneic bone marrow transplantation (allo-BMT) using a reduced preparative regimen. We evaluated in the first 3 months following allo-BMT, several immunological parameters including DC subsets, and compared these to historical results obtained in a group of myeloablative allo-BMT patients. We found an early recovery of leukocytes, CD8+ and NK lymphocytes. We also found a trend towards an improved B cell recovery. These results are somewhat in contrast to the altered immune recovery observed in the myeloablative setting. In addition, we found a significant early circulating DC recovery. Circulating blood DCs were also found to be of full donor origin as assessed by FISH in sex-mismatched pairs. Nevertheless, naive CD4 + CD45RA + T cells were found to be profoundly reduced following such regimens.Collectively, these data further enhance the overall benefits of reduced intensity regimens and the need for a stringent biological monitoring for assessment of the potential advantages of reduced intensity allo-BMT in comparison with conventional allo-BMT.