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

From the Institute of Hematology and Oncology, Department of Hematology, H. Clínic, Barcelona (CT, AUI, MG, AG, MT, FFA, MA, PM, EM); H. de la Santa Creu i Sant Pau, Barcelona (RM, JS); H. Clínico, Salamanca (JAPS); H. Germans Trias i Pujol, Badalona (MB); H. Reina Sofía, Córdoba (CH)

Correspondence: Alvaro Urbano-Ispizua, M.D., Department of Hematology, Hospital Clínic, University of Barcelona, Villarroel 170, 08036 Barcelona Spain. E-mail: aurbano{at}clinic.ub.es

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.

Key words: dendritic cells, CD16⁺ DC, reduced-intensity conditioning allogeneic stem cell transplantation.