FCCC LOGO Faculty Publications
Li B , Meng L , Tian Y , Ling J , Hu Y , Lu Q , Gao L , Wu S , Zhang Y , Hu S
Low levels of plasmacytoid dendritic cells at engraftment are a valuable prognostic indicator in children receiving allogeneic hematopoietic stem cell transplantation
Transplant Cell Ther. 2021 Apr 22
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Abstract
BACKGROUND: Early prediction and intervention are known to be critical for acute graft-versus-host disease (aGvHD) prevention and treatment. Significant progress has been made in the development of human plasma biomarkers for the risk stratification of aGvHD severity. Whether donor-derived immune cells may predict the occurrence of severe aGvHD early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains poorly understood. OBJECTIVE: The objective of this study is to evaluate the results of allo-HSCT in pediatric patients with different counts and frequency of dendritic cells (DCs) subsets at engraftment in pediatric patients within the Children's Hospital of Soochow University. STUDY DESIGN: This is a retrospective study. A total of 45 patients as a discovery cohort were enrolled from March 2018 to December 2018 within the Children's Hospital of Soochow University. The validation cohort (30 patients) was enrolled from December 2019 to May 2020. Plasma samples collected from 2016 to 2018 were used for testing ST2 and Reg3α in pediatric patients undergoing allo-HSCT. RESULTS: Patients with grade II-IV aGvHD (n=18, termed severe aGvHD) showed 3- and 6-fold fewer frequency and numbers, respectively, of plasmacytoid dendritic cells (pDCs) in the peripheral blood (PB) at the engraftment time than patients with grade 0-I aGvHD (n=27, termed no/mild aGvHD). Using the receiver operating characteristic (ROC) curve analysis, we identified the threshold of pDC level at 0.3 cells/μl as a cutoff to evaluate the difference in patients with high (>0.3 cells/μl) versus low (<0.3 cells/μl) pDC counts. Of these 45 patients, 21 (46.7%) patients had high pDCs and 24 (53.3%) patients showed low pDCs. Patients with low pDCs at the engraftment time had a significantly higher probability of developing severe aGvHD (p<0.05). The sensitivity of distinguishing severe aGvHD from no/mild aGvHD was 75% and the specificity was 94%. Additionally, low pDC patients had higher transplant-related mortality compared to high pDC patients (12.5% versus 0%). Using an additional cohort of 30 allo-HSCT patients, we validated this observation. CONCLUSION: Our findings identify that donor pDC counts in PB at the engraftment time are a valuable biomarker for predicting severe aGvHD in pediatric patients undergoing allo-HSCT.
Notes
2666-6367 Li, Bohan Meng, Lijun Tian, Yuanyuan Ling, Jing Hu, Yixin Lu, Qin Gao, Li Wu, Shuiyan Zhang, Yi Hu, Shaoyan Journal Article Transplant Cell Ther. 2021 Apr 22:S2666-6367(21)00859-9. doi: 10.1016/j.jtct.2021.04.012.