Low Counts of Plasmacytoid Dendritic Cells After Engraftment Are Associated with Higher Early Transplantation-Related Mortality in Patients Receiving Unrelated HSCT

The heterogeneous status of host immune defenses may influence the risk of infection and graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In such defense, dendritic cells (DC) which act as specialized antigen-presenting cells that bridge the innate and adaptive immune systems, and NK-cells, responsible for the innate defense against infections and residual tumor cells, are essential cell components.

To monitor the recovery of different subsets of DC and NK cells after unrelated umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PBSC) HSCT and to evaluate the impact of the distribution of these cell subsets on the outcome of the transplant.

Overall, 34 patients (median age 13y; range 1–63y) receiving a UCB (n=15), BM (n=14) or PBSC (n=5) unrelated HSCT were studied. The most common diagnosis was acute leukemia (ALL, 12 cases; AML, 10; CML, 5; aplastic anemia, 4; MDS, 2; Hodgkin lymphoma, 1; SCID, 1), a majority of patients were males (56%), and received myeloablative conditioning (MAC) regimens (73%). Antithymocyte globulin (ATG) was used in 38% and total body irraditation (TBI) in 41% of cases. Median time to neutrophil engraftment was 18 days (range: 12–45). T-cell (CD4+, CD8+, CD4−8−, CD4+8+), DC [CD123+ plasmacytoid(p)DC, CD11c+ myeloid(m)DC, and CD16+ monocytoid(mo)DC] and NK cell subsets (CD3−/CD19− 56++16− and 56+16++) were quantified by multiparametric flow cytometry at 7 sequential time points (pre-transplant, at engraftment, and at days 3, 7, 14, 21 and 60 after engraftment). Results: As compared to BM/PBSC, UCB was associated with a delayed neutrophil recovery (28 days vs. 17 days; p=0.01), and a trend to lower counts of all T-, NK- and pDC subsets, particularly for the CD4+ and CD4−/CD8− T-cells during the first 3 weeks after recovery. Conversely, no significant differences were observed between both groups as regards the distribution of mDC and moDC. The use of TBI, MAC or ATG were not associated with the reconstitution of the studied cell subsets. In contrast, patients who died from transplantation-related causes (TRM) had significantly lower counts of pDC and mDC during the first 3 weeks after HSCT. At day 21 after engraftment, the median number of pDC and mDC was 0.9 and 2.0/uL among patients who died from TRM vs. 7.1 (p=.006) and 8.4/uL (p=.01) in the remainder, respectively). Patients presenting grade II-IV acute GVHD also had significantly lower pDC counts at days 14 and 21. There was no significant association of both the hematopoietic stem cell source and the conditioning regimen on the risk of TRM or acute GVHD.

Low pDC counts in the first weeks after unrelated HSCT are associated with an increased incidence of GVHD and mortality. The precise mechanisms that might explain the role of pDC on immunity early after HSCT deserve further investigations.

No relevant conflicts of interest to declare.