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Enrichment of circulating myeloma cells by immunomagnetic beads combined with flow cytometry for monitoring minimal residual disease and relapse in patients with multiple myeloma.

Authors
  • Wang, Ningning1, 2
  • Tesfaluul, Nahom3
  • Li, Jia1
  • Gao, Xiaojuan1
  • Liu, Shuai1, 4, 5
  • Yue, Baohong6, 7, 8, 9
  • 1 Department of Laboratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. , (China)
  • 2 Department of Laboratory Medicine, the First People's Hospital of Pingdingshan, Pingdingshan, Henan, China. , (China)
  • 3 Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. , (China)
  • 4 Faculty of Laboratory Medicine, Zhengzhou University, Zhengzhou, Henan, China. , (China)
  • 5 Key Laboratory Medicine of Henan Province, Faculty of Laboratory Medicine, Zhengzhou University, Zhengzhou, Henan, China. , (China)
  • 6 Department of Laboratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. [email protected] , (China)
  • 7 Faculty of Laboratory Medicine, Zhengzhou University, Zhengzhou, Henan, China. [email protected] , (China)
  • 8 Key Laboratory Medicine of Henan Province, Faculty of Laboratory Medicine, Zhengzhou University, Zhengzhou, Henan, China. [email protected] , (China)
  • 9 Open Laboratory, Henan Province Key Subject of Clinical Medicine, Zhengzhou, Henan, China. [email protected] , (China)
Type
Published Article
Journal
Annals of Hematology
Publisher
Springer-Verlag
Publication Date
Dec 01, 2019
Volume
98
Issue
12
Pages
2769–2780
Identifiers
DOI: 10.1007/s00277-019-03833-5
PMID: 31748925
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Difficulty in regularly analyzing marrow myeloma cells (MMCs) and low frequency of circulating myeloma cells (CMCs) in blood presents challenges for monitoring minimal residual disease (MRD) in multiple myeloma (MM). We have developed a set of method for enrichment of CMCs by immunomagetic beads (IMB) combined with flow cytometry (IMB-FCM) based on CD38-APC/CD138-APC antibodies in U266-spiked samples and in 122 patient samples. U266 cell capture efficiency of CD38/CD138-IMB-FCM (6.960, 2.574) was 6- and 2-fold higher than that of FCM (1.032), and the sensitivity of FCM and IMB-FCM was 0.01% and 0.001%, respectively. In MM cohort, the positive rate of CMCs by IMB-FCM increased from 60.5~70.0 to 85~87.2% in newly diagnosed/relapsed and partial remission (PR) patients compared with by FCM (P < 0.05). Two complete remission (CR) patients contain certain amounts of CMCs by IMB-FCM while no CMCs and MMCs were detectable by FCM. Patients exhibiting PR and CR upon therapy had much lower CMC and MMC counts than newly diagnosed/relapsed patients (P < 0.005). Based on MRD measurement in BM and PB samples, all FCM-negative BM samples were also paired with FCM/IMB-FCM-negative PB samples among newly diagnosed, relapsed, and PR patients, and FCM-positive BM samples were accompanied by IMB-FCM-positive results in 88% of corresponding PB samples. CMCs strongly associated with other clinical biomarkers of disease burden, including elevated MMCs, β2-MG, sCrea, and DS and ISS stages, and more serious anemia, bone destruction, and renal impairment (P < 0.05). Logistic regression analysis revealed that elevated β2-MG and moderate-to-more anemia were significant risk factors for the presence of CMCs (P < 0.05). As a noninvasive "liquid biopsy" of monitoring MRD, the potential of IMB-FCM for CMC detection may complement or minimize bone marrow aspiration in future treatment of MM patients.

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