engleski

Impact of plasmacytoid dendritic cells (PDC) on outcome after allogeneic stem cell transplantation (allo-SCT)

The rapidly increasing use of allo-SCT emphasizes the need for identifying variables predictive of allo-SCT outcome. PDC have been proposed to play a major role in establishing immune competence. We investigated the impact of circulating PDC on clinical outcome of patients with hematological malignancies treated with allo-SCT. 79 consecutive patients were included in the analysis. The median age of the cohort was 54 (range 25-71) years and there were 42 males (53%). 44 patients (56%) were treated for myeloid malignancies, 33 patients (42%) for lymphoid malignancies and 2 patients (2%) for aplastic anemia. Stem cell source was peripheral blood in 55 patients (70%), bone marrow in 10 patients (12%) and cord blood in 14 patients (18%). Donors were identical siblings in 36 patients (45%), matched unrelated in 26 patients (33%) and mismatched unrelated in 17 patients (22%). Allo-SCT was done after a myeloablative conditioning in 9 patients (11%) and after a reduced-intensity conditioning in 70 patients (89%). PDC were identified in the blood at day 100 after allo-SCT by staining PBMC for surface markers and intracellular cytokines and analyzed on a FACSCanto flow cytometer. Patients were cathegorized by a median proportion of PDC into high PDC goup (>=0, 2% PBMC) or low PDC group (<0, 2% PBMC). The baseline characteristics of these groups were comparable. Overall, the cumulative incidence of grade II-IV acute GVHD was 36% (95%CI, 25-48%) and the cumulative incidence of extensive chronic GVHD was 37% (95%CI, 25-49%). The incidence of grade II-IV acute GVHD was significantly higher in the low PDC group (62% vs 18%, p=0.0003). Patients with grade 0–I acute GVHD secreted significantly higher amounts of IFN alpha than patients with grade II–IV acute GVHD (p=0.002), probably highlighting the deleterious impact of corticosteroids on PDC function. With a median follow-up of 21 (range, 8-29) months for the 61 surviving patients, the overall survival (OS) at 22 months was 74%(CI, 64-86%), significantly better in the „high“ PDC group (p=0.007). In the multivariate analysis, a ‘high’ PDC count measured at 100 days after allo-SCT stayed an independent predictor of an improved OS (p=0.02 ; RR=3.41 ; 95% CI, 1.19-9.78). Although we analyzed a rather heterogenous group of patients, precluding establishing the definitive role of PDC after allo-SCT, we can reasonably envision that monitoring of PDC may be useful for patients’ management, and may have a significant impact on the probability of a favorable outcome of allo-SCT.

pDC; outcome; stem cell transplantation

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