Impact of Dendritic Cell CD16+ Recovery on Outcome after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation.

Abstract

Dendritic cells (DCs) play a critical role in the regulation of alloimmune responses. Therefore, the number and function of these cells after allogeneic stem cell transplantation (allo-SCT) might influence patients' outcome, an aspect scarcely investigated, particularly in the setting of reduced-intensity conditioning transplants (allo-RIC). Against this background, we studied DCs recovery in 92 patients (median age 50, range 17–67; male 57%), undergoing allo-RIC from HLA identical donors in five Spanish institutions between October 2002 and December 2004. Median follow up was 250 days (range, 25–708). Conditioning regimen consisted on fludarabine 150 mg/m2 + melphalan 140 mg/m2 for lymphoid malignancies (n=54), and fludarabine 150 mg/m2 + busulphan 10 mg/kg for myeloid malignancies (n=38); 71 (90%) patients had advanced disease. Peripheral blood samples were obtained at 1, 3, 6 and 12 months after transplant. DCs were identified as positive for HLA-DR and negative for lineage markers (CD3, CD14, CD19, and CD56). The expression of CD33, CD123 and CD16 was used to identify DC1, DC2 and DC CD16+ subsets, respectively; the immunophenotypic analysis being centralized at a single institution. The most significant association with clinical outcome was found with DC CD16+ levels at three months after transplantantation. Thus, at that time point, patients with a DC CD16+ count lower than the median (<1.5×104/mL) had a significantly higher incidence of relapse (59% vs. 45%; p=0.04), more transplant related mortality (30% vs. 0%; p=0.01), worse event free survival (EFS) (24% vs. 51%; p=0.002) and overall survival (0% vs. 55%; p=0.002). Only two factors were associated with worse EFS in the multivariate analysis: autologous transplantation before allo-RIC (RR 6.5, 95%CI 1.6–26.2; p=0.008), and DC CD16+ count lower than the median at +3m (RR 13.1; 95% CI 1.7–100.5; p=0.01). In conclusion, this study shows that besides a well-known poor prognostic factor (i.e., prior autologous transplantation) a low DC CD16+ count at three months after allo-RIC is associated with a poorer outcome, this probably reflecting impaired immunosurveillance mechanisms.