Hematology and Stem Cell Transplantation, Fondazione Policlinico Campus Bio-Medico, Rome, Italy.
Transfusion Medicine and Cell Therapy, Fondazione Policlinico Campus Bio-Medico, Rome, Italy.
Chemotherapy. 2023;68(3):138-142. doi: 10.1159/000529665. Epub 2023 Mar 9.
Neoangiogenesis has a crucial role in multiple myeloma (MM), and circulating endothelial cells (CECs) contribute to neovascularization by inducing tumor progression and metastasis and by repairing damage to bone marrow vasculature after stem cell transplantation (HSC). We recently proved in a national multicenter study the possibility to reach a high-level standardization in CEC count and analysis based on a polychromatic flow cytometry Lyotube (BD). Our study aimed at assessing the kinetics of CECs in patients with MM undergoing autologous hematopoietic stem cell transplantation (Au-HSCT).
Blood samples for analysis were collected at different time points before (T0, T1) and after (T2, T3, T4) Au-HSCT. For each sample, 20 × 106 leukocytes were processed as already described (Lanuti 2016 e 2018) through a multistep procedure. CECs were eventually identified as 7-ADDneg/Syto16pos/CD45neg/CD34pos/CD146pos.
Twenty-six MM patients were enrolled in the study. Overall, we observed a constant increase of CECs values from T0 to T3 (day of neutrophil engraftment) followed by decrease at T4 (100 days after transplantation). Using the median value of CECs at T3, we could define a cut-off concentration of 618/mL, with patients with more infective complications having CECs above that value (9/13 vs. 2/13; p = 0.005).
CECs value may be a function of endothelial damage caused by conditioning regimen, as suggested by the increase of their level during the engraftment period. A more severe endothelial damage is reflected by the increase of infective complications in patients with higher CECs value at T3.
新血管生成在多发性骨髓瘤(MM)中起着关键作用,循环内皮细胞(CEC)通过诱导肿瘤进展和转移以及修复干细胞移植(HSC)后骨髓血管损伤,促进新血管生成。我们最近在一项全国多中心研究中证明,基于多色流式细胞术 Lyotube(BD),有可能实现 CEC 计数和分析的高水平标准化。我们的研究旨在评估接受自体造血干细胞移植(Au-HSCT)的 MM 患者 CEC 的动力学。
在 Au-HSCT 前(T0、T1)和后(T2、T3、T4)不同时间点采集用于分析的血液样本。对于每个样本,按照已经描述的方法(Lanuti 2016 年和 2018 年)通过多步程序处理 20×106 个白细胞。CEC 最终被鉴定为 7-ADDneg/Syto16pos/CD45neg/CD34pos/CD146pos。
共有 26 名 MM 患者入组该研究。总体而言,我们观察到 CECs 值从 T0 到 T3(中性粒细胞植入日)持续增加,随后在 T4(移植后 100 天)下降。使用 T3 时的 CECs 中位数,可以定义一个 618/mL 的截止值,具有更多感染性并发症的患者的 CECs 值高于该值(9/13 比 2/13;p=0.005)。
CECs 值可能是由预处理方案引起的内皮损伤的函数,这是在植入期间其水平增加所表明的。在 T3 时 CECs 值较高的患者中,感染性并发症的增加反映了内皮损伤更严重。