Low Counts of Plasmacytoid Dendritic Cells after Engraftment Are Associated with High Early Mortality after Allogeneic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2015 Jul;21(7):1223-9. doi: 10.1016/j.bbmt.2015.03.010. Epub 2015 Mar 17.

Abstract

Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage-; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage-, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.

Keywords: Dendritic cells; Graft-versus-host disease; Immune recovery; Nonrelapse mortality; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Bone Marrow Transplantation / adverse effects*
  • Cell Count
  • Cell Lineage / immunology
  • Child
  • Child, Preschool
  • Cord Blood Stem Cell Transplantation / adverse effects*
  • Dendritic Cells / classification
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology*
  • Female
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality*
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Male
  • Middle Aged
  • Myeloablative Agonists / therapeutic use
  • Siblings
  • Survival Analysis
  • Transplantation Conditioning*
  • Transplantation, Homologous
  • Unrelated Donors

Substances

  • Immunosuppressive Agents
  • Myeloablative Agonists