Higher Counts Of Plasmacytoid Dendritic Cells In The Allograft Are Associated Increased Risk Of Acute Gvhd After Stem Cell Transplantation

Recent studies suggest that higher circulating dendritic cell counts after hematopoietic stem cell transplantation (HSCT) may be associated with lower risk of graft versus host disease (GVHD) and mortality. Plasmacytoid dendritic cells (pDC) have tolerogenic properties and may explain such results. However, only a few studies with conflicting results analyzed pDC counts in the allograft, mainly in the related HSCT setting.

To compare pDC counts among different cell sources [umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PBSC)] and to correlate the pDC content on the graft with main HSCT outcomes.

Plasmacytoid dendritic cells (pDC: lineage negative, HLA-DR+ and CD123+) were quantified by multiparametric flow cytometry in the graft just before its infusion. Overall, 77 patients (49 male; median age 21y, range 1-74y) receiving UCB (n=26), BM (n=34) or PBSC (n=17) HSCT from unrelated (n=67) or related donors (n=10) were studied. The most common diagnosis was acute leukemia (ALL, 30 cases; AML, 22). Most patients received myeloablative conditioning regimens (n=47, 61%). Antithymocyte globulin was used in 30 patients (39%) and total body irradiation in 41 (53%). Median follow up time was 15 months (4-33).

Median time to neutrophil engraftment was 19 days (range: 11-49) and 35 days to platelet engraftment (range 2-176). The median percentage of pDC on the graft was 0.20% of non erythroid nucleated cells (range: 0.02-0.67) and no differences were noticed among sources. Cumulative incidence (CI) of grade II-IV acute GVHD at 100 days was higher on patients receiving grafts with higher percentages of pDC (22% for patients with less than 0.15%pDC graft content vs. 52% for patients receiving grafts with higher counts, p=0.026). There was no impact of graft pDC content on mortality, relapse, chronic GVHD or overall survival. In a multivariate analysis, graft pDC content remains an independent risk factor for acute GVHD [HR: 3.0, CI (95%): 1.15-7.8].

Higher pDC graft percentages were associated with increased risk of acute GVHD, but had no impact on non-relapse mortality or survival. The precise role of pDC on immunity after HSCT deserves further investigation and might be related not only to pDC biology itself but to the chronology of the pDC interaction with host antigens.

No relevant conflicts of interest to declare.