Peripheral Blood Plasmacytoid Dendritic Cells at Day 100 Can Predict Outcome after Allogeneic Stem Cell Transplantation
Abstract
The rapidly increasing use of allogeneic stem cell transplantation (allo-SCT) emphasizes the need for identifying variables predictive of its outcome. Plasmacytoid dendritic cells (pDCs) play a major role in establishing immune competence and in several autoimmune diseases. Thus, we investigated whether pDCs might influence the outcome of patients after allo-SCT in 79 consecutive patients who underwent this procedure. pDCs were identified in the blood of patients at day 100 after allo-SCT by staining peripheral blood mono-nuclear cells for surface markers and intracellular cytokines and analyzing them on a flow cytometer. We found the pDC level at day 100 was not influenced by patient or graft characteristics, and only the absence of previous grades II to IV acute graft-versus-host disease was significantly associated with higher levels of blood pDCs after allo-SCT (OR, .67; 95% CI, .54 to .83; P ¼ .0004). Using the median value of pDCs at day 100 to divide the patients into 2 distinct groups, we observed that a low pDC level was correlated with a worse overall survival (55% versus 86%, P ¼ .007). In a multivariate analysis, only low pDC level (OR, 3.41; 95% CI, 1.19 to 9.79; P ¼ .02) and older patient age (OR, 5.16; 95% CI, 1.15 to 23.14; P ¼ .03) were significantly predictive of increased risk of death. We conclude that monitoring of pDC may be useful for patient management and may have a significant impact on the probability of a favorable outcome of allo-SCT. INTRODUCTION Allogeneic stem cell transplantation (allo-SCT) has evolved into a curative therapy for a variety of hematological and nonhematological malignancies. In the treatment of the former, high-intensity conditioning therapy before allo-SCT eradicates malignant cells, and the infusion of donor stem cells enables reconstitution of the recipient's hematopoietic system and also triggers a graft-versus-leukemia (GVL) effect. However, the main limitation of treating a broader spectrum of diseases and patients with allo-SCT is graft-versus-host disease (GVHD), a reaction closely associated to GVL. Both GVHD and GVL occur when donor T lymphocytes respond to genetically defined proteins on host cells. Den-dritic cells (DCs) are key antigen-presenting cells that
Domains
Cancer
Origin : Files produced by the author(s)
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