Circulating plasma cells (CPCs) are frequently noted in variable frequencies in the entire spectrum of plasma cells neoplasms. With advent of high sensitivity multi-parametric flow cytometry, it is not only possible to detect CPCs present in very low numbers, but also to categorise them into circulating tumor plasma cells (CTPCs) and circulating normal plasma cells (CNPCs), based on their marker-profile. This study used multi-colour flow cytometry to evaluate the load of both CTPCs & CNPCs at the time of diagnosis and at six months’ time-point of therapy, and evaluated associations of both with clinical and laboratory parameters. Twenty one newly diagnosed MM patients were enrolled. Six to nine millilitres of EDTA-anticoagulated peripheral blood sample was used for flow cytometry. A ten colour antibody panel was used for analysis of CPCs, which were categorised further into CTPCs and CNPCs. Approximately 4.8 million events were acquired for the analysis. The percentage &absolute numbers of CTPCs and CNPCs were noted and the proportion of CTPCs out of all CPCs (CTPCs + CNPCs) were also calculated for evaluating their statistical associations. All 21 patients of newly diagnosed MM showed presence of CPCs (CTPCs and/or CNPCs) at the time of diagnosis. The CTPCs were detected in 76 % of the study population. The median percentage and absolute counts of CTPCs were 0.52 % and 54.9 cells /µL, respectively. CNPCs were found in 95 % and the median percentage and absolute counts of CNPCs were 0.025 % and 2.66 cells/µL. After six months of therapy, CPCs (CTPCs and/or CNPCs) were found in all nine patients evaluated for this assay. CTPCs were found 33 %, with a median of 0.075 % and CNPCs were found in 89 % with a median of 0.01 %. Our study showed that the load of CTPCs was found to be higher in patients with presence of lytic bone lesions, plasmacytoma, presence of PCs on peripheral blood film by light microscopy, presence of Chr 1p32 deletion, expression of CD56 and CD81 on CTPCs, and in patients with absence of very good partial response (VGPR). Conversely, the load of CTPCs was significantly lower in patients with concomitant amyloidosis. Also, percentage of bone marrow plasma cells exhibited a significant positive correlation with the absolute count of CTPCs. We observed that the mean percentage of CNPCs was significantly higher in female patients. The load of CNPCs was lower in patients with thrombocytopenia and with hypoalbuminemia. Increased burden of CTPCs was associated with presence of lytic lesions, plasmacytomas, Chr 1p32 deletion, expression of CD56 and CD81 on tumor cells and with failure to achieve very good partial response. The CNPCs were lower in patients with thrombocytopenia and with hypoalbuminemia. To best ot our knowledge, this is the first study from India on the relevance of circulating tumor plasma cells and the first study in the world to analyse the associations of circulating normal plasma cells in newly diagnosed patients of multiple myeloma. The study also highlights the utility of multi-parametric flow cytometry in identification and enumeration of circulating plasma cells. Circulating plasma cells indicates poorer outcomes in patients of multiple myeloma. Twenty one newly diagnosed multiple myeloma patients were evaluated by flow cytometry to enumerate and characterise circulating tumor plasma cells (CTPCs) and circulating normal plasma cells (CNPCs). Higher load of CTPCs correlated with known poor prognostic markers and poor response to therapy.

中文翻译：

---

新诊断多发性骨髓瘤患者循环正常浆细胞和肿瘤浆细胞的检测及其与临床和实验室参数的关系

循环浆细胞（CPC）在浆细胞肿瘤的整个谱系中经常以不同的频率出现。随着高灵敏度多参数流式细胞术的出现，不仅可以检测到数量极少的CPC，还可以根据其分布情况将其分为循环肿瘤浆细胞（CTPC）和循环正常浆细胞（CNPC）。标记轮廓。本研究使用多色流式细胞术评估诊断时和治疗六个月时间点时 CTPC 和 CNPC 的负荷，并评估两者与临床和实验室参数的关联。纳入了 21 名新诊断的 MM 患者。使用 6 至 9 毫升 EDTA 抗凝外周血样本进行流式细胞术。使用十色抗体组对 CPC 进行分析，CPC 进一步分为 CTPC 和 CNPC。获取了大约 480 万个事件用于分析。记录了 CTPC 和 CNPC 的百分比和绝对数量，并计算了 CTPC 在所有 CPC 中的比例（CTPC + CNPC）以评估它们的统计关联。所有 21 名新诊断 MM 患者在诊断时均显示存在 CPC（CTPC 和/或 CNPC）。76% 的研究人群中检测到了 CTPC。CTPC 的中位百分比和绝对计数分别为 0.52 % 和 54.9 个细胞/μL。CNPC 的检出率为 95%，CNPC 的中位百分比和绝对计数分别为 0.025% 和 2.66 个细胞/μL。经过六个月的治疗后，在本次测定评估的所有 9 名患者中均发现了 CPC（CTPC 和/或 CNPC）。CTPC 的检出率为 33%，中位数为 0.075%，CNPC 的检出率为 89%，中位数为 0.01%。我们的研究表明，存在溶骨性病变、浆细胞瘤、光镜下外周血涂片上存在 PC、存在 Chr 1p32 缺失、CTPC 上表达 CD56 和 CD81 以及没有非常好的部分缓解（VGPR）的患者。相反，伴有淀粉样变性的患者 CTPC 负荷显着较低。此外，骨髓浆细胞百分比与 CTPC 绝对计数呈显着正相关。我们观察到，女性患者的 CNPC 平均百分比明显更高。血小板减少症和低蛋白血症患者的 CNPC 负荷较低。CTPC 负担的增加与溶解性病变、浆细胞瘤、Chr 1p32 缺失、肿瘤细胞上 CD56 和 CD81 的表达以及未能实现非常好的部分缓解有关。血小板减少症和低蛋白血症患者的 CNPC 较低。据我们所知，这是印度第一项关于循环肿瘤浆细胞相关性的研究，也是世界上第一项分析新诊断的多发性骨髓瘤患者循环正常浆细胞关联性的研究。该研究还强调了多参数流式细胞术在循环浆细胞的识别和计数中的实用性。循环浆细胞表明多发性骨髓瘤患者的预后较差。通过流式细胞术对 21 名新诊断的多发性骨髓瘤患者进行评估，以计数和表征循环肿瘤浆细胞 (CTPC) 和循环正常浆细胞 (CNPC)。CTPC 负荷较高与已知的不良预后标志物和治疗反应不良相关。