Kinetics of recovery of dendritic cell subsets after reduced-intensity conditioning allogeneic stem cell transplantation and clinical outcome

Haematologica. 2007 Dec;92(12):1655-63. doi: 10.3324/haematol.11076.

Abstract

Background and objectives: Dendritic cells (DC) play a critical role in the regulation of alloimmune responses and might influence the outcome of allogeneic stem cell transplantation (allo-SCT). We studied the clinical relevance of early reconstitution of DC after reduced-intensity conditioning allo-SCT (allo-RIC).

Design and methods: This study included 79 adult patients undergoing allo-RIC from HLA-identical siblings. Peripheral blood samples were drawn from patients at 1 month (+1m) and 3 months (+3m) after the transplant. DC were identified as positive for HLA-DR and negative for CD3, CD19, CD14 and CD56. The expression of CD33, CD123 and CD16 was used to identify myeloid DC, plasmacytoid DC and CD16(+) DC subpopulations, respectively.

Results: Patients whose DC count at +1m was lower than the median had a higher probability of treatment-related mortality (TRM) (60% vs 12%; p=0.02), poorer overall survival (OS) (15% vs 45%; p=0.002) and worse event-free survival (EFS) (20% vs 38%; p=0.03). A multivariate analysis confirmed that low DC counts had a detrimental effect on OS (RR 3.2; p=0.007), relapse (RR 4.1; p=0.01), and EFS (RR 6; p=0.001). Low CD16(+) DC counts were observed to have a detrimental effect on EFS, which was due to both a higher incidence of deaths caused by infections (50% vs 0%, p=0.05) and a higher incidence of relapse (57% vs 50%; p=0.03). Indeed, the number of CD16(+) DC at +3 m was the most important prognostic factor for EFS (RR 6; p=0.001). Interpretations and Conclusions This study shows the clinical importance of DC recovery, especially of the CD16(+) DC subset, in the outcome of patients treated with allo-RIC.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / immunology
  • Blood Cell Count
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Disease-Free Survival
  • Female
  • Hematologic Neoplasms / immunology*
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology
  • Plasma Cells / immunology*
  • Plasma Cells / pathology
  • Recovery of Function / immunology*
  • Retrospective Studies
  • Spain
  • Stem Cell Transplantation*
  • Transplantation Conditioning*
  • Transplantation, Homologous

Substances

  • Antigens, CD