Plasmacytoid dendritic cell count on day 28 in HLA-matched related allogeneic peripheral blood stem cell transplant predicts the incidence of acute and chronic GVHD

Biol Blood Marrow Transplant. 2008 Mar;14(3):344-50. doi: 10.1016/j.bbmt.2007.12.494.

Abstract

Dendritic cells (DC) are antigen-presenting cells involved in induction and regulation of immune responses. We investigated the impact of the number of infused and day 28 dendritic cells on the development of acute and chronic GVHD (aGVHD, cGVHD). Monocytoid (MC) and plasmacytoid (PC) dendritic cells were characterized as lin(-)HLA-DR(+)CD11c(+) and lin(-)HLA-DR(+)CD123(+), respectively. Sixty-eight consecutive patients who underwent HLA matched related granuloyte-colony stimulating factor (G-CSF) mobilized allogeneic PBSCT, from February 2005 to May 2006, were included in the analysis. Twenty-three patients developed aGVHD (grade II-IV) and 21 patients had cGVHD. On a univariate analysis the day 28 total DC and the day 28 MC and PC dendritic cells as continuous variables were significantly associated with development of aGVHD and cGVHD. Using an ROC plot analysis a cutoff value for total DC = 10.7/microL, MC = 9.7/microL, and PC = 4.5/microL on day 28 gave the highest likelihood ratios for aGVHD (2.7, 2.14, and 3.29, respectively). On a multivariate analysis, a low day 28 PC (<or=4.5/microL) together with patient age retained their risk for aGVHD (hazard ratio [HR] = 65.1 and 1.0, P-values .000 and .036, respectively), whereas for cGVHD only a low day 28 PC remained significant (HR = 11.8, P = .008). These results suggest that the PC dendritic cell count in the peripheral blood on day 28 is a strong predictor for development of GVHD in recipients of an allogeneic matched related PBSCT.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • CD11c Antigen / blood*
  • Child
  • Child, Preschool
  • Chronic Disease
  • Dendritic Cells* / pathology
  • Female
  • Graft vs Host Disease / blood*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • HLA-DR Antigens / blood*
  • Hematologic Diseases / blood
  • Hematologic Diseases / complications
  • Hematologic Diseases / mortality
  • Hematologic Diseases / therapy
  • Hematopoietic Stem Cell Mobilization
  • Histocompatibility Testing
  • Humans
  • Incidence
  • Interleukin-3 Receptor alpha Subunit / blood*
  • Leukocyte Count*
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation* / mortality
  • Plasma Cells* / pathology
  • Predictive Value of Tests
  • Receptors, Interleukin-3 / blood*
  • Risk Factors
  • Time Factors
  • Transplantation, Homologous

Substances

  • CD11c Antigen
  • HLA-DR Antigens
  • IL3RA protein, human
  • Interleukin-3 Receptor alpha Subunit
  • Receptors, Interleukin-3
  • Granulocyte Colony-Stimulating Factor