Haematologica (Dec 2007)

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

  • Carme Talarn,
  • Alvaro Urbano-Ispizua,
  • Rodrigo Martino,
  • José Antonio Pérez-Simón,
  • Montserrat Batlle,
  • Concepción Herrera,
  • Miquel Granell,
  • Anna Gaya,
  • Montserrat Torrebadell,
  • Francesc Fernández-Avilés,
  • Marta Aymerich,
  • Pedro Marín,
  • Jorge Sierra,
  • Emili Montserrat

DOI
https://doi.org/10.3324/haematol.11076
Journal volume & issue
Vol. 92, no. 12

Abstract

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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.