Enumeration of bone marrow plasmacytoid dendritic cells by multiparameter flow cytometry as a prognostic marker following allogeneic hematopoietic stem cell transplantation

Abstract

Plasmacytoid dendritic cells (pDCs) promote tolerance in solid organ transplants and hematopoietic stem cell transplantation (HSCT). pDCs originate from CD34⁺ hematopoietic progenitors. Following allogeneic hematopoietic stem cell transplant (allo-HSCT), pDC reconstitution in the BM and PB gradually attain levels similar to those in healthy individuals. We have investigated the recovery of pDC following allo-HSCT as a means to predict successful marrow engraftment. We retrospectively studied immune reconstitution of pDC in the BM of 48 patients following allo-HSCT for initial diagnoses of leukemia or other malignancies. Multi-parameter flow cytometry was used to detect the CD45⁺CD123^bright HLA-DR⁺ CD4^low pDCs in BM aspirates at 2-14months (median 6months) post allo-HSCT. Percentages of pDCs were analyzed along with engraftment, acute graft-versus-host disease (aGVHD), event-free survival, relapse and death over a period of up to 39months (median 30) following HSCT. We report that higher levels of pDCs in the BM post-HSCT are associated with successful engraftment, less severity of aGVHD, lower relapse rate, higher event-free survival and overall survival (P value <0.05 for all). pDC levels detected at a shorter time interval 2-8months (median 5months) following HSCT also showed similar results. We conclude that pDC numbers are associated with HSCT engraftment and overall survival. Flow cytometry offers rapid quantification of pDCs as an early predictor of outcome following HSCT.

Keywords: Allogeneic hematopoietic stem cell transplantation; Flow cytometry; Outcome; Plasmacytoid dendritic cells; Prognosis.