Department of Hematology, Children Hospital, Soochow University, Suzhou, China.
Department of Hematology, Children Hospital, Soochow University, Suzhou, China; Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, Pennsylvania.
Transplant Cell Ther. 2021 Jul;27(7):611.e1-611.e12. doi: 10.1016/j.jtct.2021.04.012. Epub 2021 Apr 22.
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. The objective of this retrospective study was to evaluate the results of allo-HSCT in pediatric patients with different counts and frequencies of dendritic cell (DC) subsets at engraftment in pediatric patients at the Children's Hospital of Soochow University. A total of 45 patients as a discovery cohort were enrolled from March 2018 to December 2018 at the hospital. 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. 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 a receiver operating characteristic curve analysis, we identified the threshold of pDC level at 0.3 cell/μL as a cutoff to evaluate the difference in patients with high (>0.3 cell/μL) versus low (<0.3 cell/μL) pDC counts. Of these 45 patients, 21 (46.7%) had a high number of pDCs and 24 (53.3%) had low pDCs. The patients with low pDCs at the time of engraftment had a significantly higher probability of developing severe aGVHD (P < .05). The sensitivity of distinguishing severe aGVHD from no/mild aGVHD was 75%, and the specificity was 94%. In addition, the low pDC patients had higher transplantation-related mortality compared with the high pDC patients (12.5% versus 0%). Using an additional cohort of 30 allo-HSCT patients, we validated this observation. Our findings demonstrate that donor pDC count in PB at the time of engraftment is a valuable biomarker for predicting severe aGVHD in pediatric patients undergoing allo-HSCT.
早期预测和干预对于急性移植物抗宿主病(aGVHD)的预防和治疗至关重要。在开发用于预测 aGVHD 严重程度风险分层的人类血浆生物标志物方面已经取得了重大进展。然而，供体来源的免疫细胞是否可以在异基因造血干细胞移植(allo-HSCT)后早期预测严重 aGVHD 的发生仍知之甚少。本回顾性研究的目的是评估苏州大学儿童医院在植入时具有不同树突状细胞(DC)亚群计数和频率的儿科患者接受 allo-HSCT 的结果。从 2018 年 3 月至 2018 年 12 月，共招募了来自医院的 45 名患者作为发现队列。验证队列(30 名患者)于 2019 年 12 月至 2020 年 5 月入组。从 2016 年至 2018 年收集的血浆样本用于检测接受 allo-HSCT 的儿科患者的 ST2 和 Reg3α。在植入时，发生 II-IV 级 aGVHD(n=18;称为严重 aGVHD)的患者外周血(PB)中浆细胞样树突状细胞(pDC)的频率和数量分别减少了 3 倍和 6 倍，而发生 0-I 级 aGVHD(n=27;称为无/轻度 aGVHD)。使用受试者工作特征曲线分析，我们确定了 pDC 水平为 0.3 个细胞/μL 的阈值作为评估高(>0.3 个细胞/μL)与低(<0.3 个细胞/μL) pDC 计数患者之间差异的截止值。在这 45 名患者中，有 21 名(46.7%)的 pDC 数量较高，有 24 名(53.3%)的 pDC 数量较低。植入时 pDC 数量较低的患者发生严重 aGVHD 的概率显著更高(P<0.05)。区分严重 aGVHD 和无/轻度 aGVHD 的敏感性为 75%，特异性为 94%。此外，与高 pDC 患者相比，低 pDC 患者的移植相关死亡率更高(12.5%对 0%)。使用另外 30 名 allo-HSCT 患者的队列验证了这一观察结果。我们的研究结果表明，在接受 allo-HSCT 的儿科患者中，植入时供体 PB 中的 pDC 计数是预测严重 aGVHD 的有价值的生物标志物。
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