Impact of Plasmacytoid Dendritic Cell (PDC) Recovery on Outcome after Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (Allo-SCT).

Dendritic cells (DCs) are crucial in the induction of immune responses. Among DC subsets, the reconstitution of the natural type I-interferon-producing plasmacytoid DCs (PDC) has been proposed to play a major role in establishing immune competence, given the capacity of PDCs to efficiently expand either specific cytotoxic T lymphocytes, or to promote regulatory T cells, contributing to an impaired immune response. Therefore, we investigated the impact of circulating PDCs measured at the third month after RIC-allo-SCT, in 54 patients with hematological and non-hematological malignancies who received a RIC-allo-SCT from an HLA-identical sibling, in order to determine whether this could provide a convenient indicator for long term outcome. The median absolute count of PDCs measured at 3 months after RIC-allo-SCT was 0.725/μL (range, 0–23.2). In a multiple logistic regression analysis including all relevant parameters (demographic and graft characteristics, RIC regimens, CMV infections, and acute GVHD), only the absence of clinically significant grade II-IV acute GVHD was associated with an improved PDC recovery at 3 months (P=0.003; OR=6.4; 95%CI, 1.9–22). Being the major type I IFN-secreting cells, we also investigated whether PDCs recovered after allo-SCT are functional in response to viral stimulation. Patients experiencing grade 0-I acute GVHD could secrete significantly higher amounts of IFN-alpha as compared to patients with grade II–IV aGVHD (mean, 91 pg/ml vs. 0 pg/ml respectively; P=0.002), likely highlighting the deleterious impact of corticosteroids therapy on PDC function. The CD34+ stem cell dose and other lymphoid subsets infused with the allograft did not affect PDC recovery. Though PDC count could not predict death from progression or relapse, patients with a “high” PDC recovery profile had an improved overall survival (OS; P=0.03), in contrast to patients with a “low” PDC recovery profile who had an increased incidence of late transplant-related mortality (GVHD, infections) (P=0.03). In addition, the overall incidence of late infections (viral, fungal and bacterial) was significantly higher in the “low” PDC recovery group as compared to the “high” PDC recovery group (59% vs. 19%; P=0.002), illustrating the importance of PDCs in anti-infectious immune responses. In a multivariate analysis, only a “high” PDC count was significantly predictive of a decreased risk of death (P=0.04; RR=0.34; 95%CI, 0.12–0.96). The role and impact of rare immune effector cells would tend to be more evident in truly RIC and less toxic regimens. In this study, we could show that monitoring of PDCs may be useful for patients’ management (closer surveillance, infection prophylaxis…), and may have a significant impact on the probability of a favorable outcome in the context of RIC-allo-SCT.