Work

Low circulating dendritic cell count after allogeneic stem cell transplantation (SCT) predicts death, relapse, and acute graft-versus-host disease (AGVHD)

Year: 2004

Type: article

Abstract: Dendritic cells (DC) are key antigen presenting cells, with a potential role in tumor vaccines. We investigated the hypothesis that early reconstitution of DC around the time of engraftment after allogeneic SCT improves survival. We also correlated DC reconstitution with complications of relapse and AGVHD. Fifty patients were transplanted between February 2000 and March 2003 with a median follow up of 501 days (range 136–1263). Most patients received blood stem cells (92%), and the remainder bone marrow, from HLA matched sibling donors for predominantly high risk hematologic malignancies. Around the time of sustained neutrophil engraftment of >500 cells/mm3, peripheral blood was analyzed by flow cytometry for DC as lineage negative, HLA-DR positive, and further divided as DC1 (CD11c+) and DC2 (CD123+). Patients were divided into two groups of either low (n = 23) or high (n = 27) absolute DC count based on clustering technique determination. Patients with lower DC count (<4.97 cells/mm3) had a significantly worse survival by Kaplan-Meier analysis (p = 0.009), increased incidence of relapse (p = 0.002), a higher incidence of AGVHD onset (p = 0.0005) and a composite end point of relapse or death (p = 0.002). A Cox-proportional Hazard multivariate model adjusted for important covariates confirmed that low DC count is independently associated with death (HR 3.8; 95% CI 1.3, 11.3; p = 0.02), time to relapse (HR 10.2; 95% CI 2.2, 47.2; p = 0.003) and in the development of severe AGVHD (HR = 2.7; 95% CI 1.2, 6.4; p = 0.02). The sensitivity and specificity of low DC count in predicting death or relapse after transplantation is 73% and 75% respectively with a positive predictive value (PPV) of 70% and negative predictive value (NPV) of 78%. To further delineate DC functionally, we studied DC1 and DC2 phenotypes, and the failure rates remained higher in the low cell count groups. In addition, DC recovery was independent of DC infused or patient DC counts prior to transplant. Our data suggest that, at least for peripheral blood SCT, the number of DC in the graft has no impact while the numbers of DC ultimately reconstituted in the recipient make the difference. In summary, our findings are unique for describing an early easily reproducible clinical indicator for adverse clinical outcomes such as relapse, death, and AGVHD after hematopoietic SCT. This finding should allow for early recognition of patients and studies for potential therapeutic interventions.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2003.12.104