scholarly journals Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors [see comments]

Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 636-640 ◽  
Author(s):  
W Brugger ◽  
KJ Bross ◽  
M Glatt ◽  
F Weber ◽  
R Mertelsmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Cell Recruitment ◽  
Stage Iv Breast Cancer

Abstract Peripheral blood progenitor cells (PBPCs) are increasingly used for autografting after high-dose chemotherapy. One advantage of PBPCs over the use of autologous bone marrow would be a reduced risk of tumor-cell contamination. However, the actual level of tumor cells contaminating PBPC harvests is poorly investigated. It is currently not known whether mobilization of PBPCs might also result in mobilization of tumor cells. We evaluated 358 peripheral blood samples from 46 patients with stage IV or high-risk stage II/III breast cancer, small cell (SCLC) or non- small cell (NSCLC) lung cancer, as well as other advanced malignancies for the detection of epithelial tumor cells. Monoclonal antibodies against acidic and basic cytokeratin components and epithelial antigens (HEA) were used in an alkaline phosphatase-anti-alkaline phosphatase assay with a sensitivity of 1 tumor cell within 4 x 10(5) total cells. Before initiation of PBPC mobilization, circulating tumor cells were detected in 2/7 (29%) patients with stage IV breast cancer and in 2/10 (20%) patients with extensive-disease SCLC, respectively. In these patients, an even higher number of circulating tumor cells was detected after chemotherapy with VP16, ifosfamide, and cisplatin (VIP) followed by granulocyte colony-stimulating factor (G-CSF). This approach has previously been shown to be highly effective in mobilizing PBPCs. In the 42 patients without circulating tumor cells during steady state, tumor cells were mobilized in 9/42 (21%) patients after VIP+G-CSF induced recruitment of PBPCs. The overall incidence of tumor cells varied between 4 and 5,600 per 1.6 x 10(6) mononuclear cells analyzed. All stage IV breast cancer patients and 50% of SCLC patients were found to concomitantly mobilize tumor cells and PBPCs. Kinetic analyses showed two patterns of tumor cell recruitment depending on the presence or absence of bone marrow disease: (1) early after chemotherapy (between days 1 and 7) in patients without marrow infiltration, and (2) between days 9 and 16 in patients with marrow infiltration, ie, within the optimal time period for the collection of PBPCs. We show that there is a high proportion of patients with circulating tumor cells under steady-state conditions, and in addition a substantial risk of concomitant tumor cell recruitment upon mobilization of PBPCs, particularly in stage IV breast cancer patients with bone marrow infiltration. The biologic and clinical significance of this finding is unknown at present.

scholarly journals Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors [see comments]

Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 636-640 ◽  
Author(s):  
W Brugger ◽  
KJ Bross ◽  
M Glatt ◽  
F Weber ◽  
R Mertelsmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Cell Recruitment ◽  
Stage Iv Breast Cancer

Peripheral blood progenitor cells (PBPCs) are increasingly used for autografting after high-dose chemotherapy. One advantage of PBPCs over the use of autologous bone marrow would be a reduced risk of tumor-cell contamination. However, the actual level of tumor cells contaminating PBPC harvests is poorly investigated. It is currently not known whether mobilization of PBPCs might also result in mobilization of tumor cells. We evaluated 358 peripheral blood samples from 46 patients with stage IV or high-risk stage II/III breast cancer, small cell (SCLC) or non- small cell (NSCLC) lung cancer, as well as other advanced malignancies for the detection of epithelial tumor cells. Monoclonal antibodies against acidic and basic cytokeratin components and epithelial antigens (HEA) were used in an alkaline phosphatase-anti-alkaline phosphatase assay with a sensitivity of 1 tumor cell within 4 x 10(5) total cells. Before initiation of PBPC mobilization, circulating tumor cells were detected in 2/7 (29%) patients with stage IV breast cancer and in 2/10 (20%) patients with extensive-disease SCLC, respectively. In these patients, an even higher number of circulating tumor cells was detected after chemotherapy with VP16, ifosfamide, and cisplatin (VIP) followed by granulocyte colony-stimulating factor (G-CSF). This approach has previously been shown to be highly effective in mobilizing PBPCs. In the 42 patients without circulating tumor cells during steady state, tumor cells were mobilized in 9/42 (21%) patients after VIP+G-CSF induced recruitment of PBPCs. The overall incidence of tumor cells varied between 4 and 5,600 per 1.6 x 10(6) mononuclear cells analyzed. All stage IV breast cancer patients and 50% of SCLC patients were found to concomitantly mobilize tumor cells and PBPCs. Kinetic analyses showed two patterns of tumor cell recruitment depending on the presence or absence of bone marrow disease: (1) early after chemotherapy (between days 1 and 7) in patients without marrow infiltration, and (2) between days 9 and 16 in patients with marrow infiltration, ie, within the optimal time period for the collection of PBPCs. We show that there is a high proportion of patients with circulating tumor cells under steady-state conditions, and in addition a substantial risk of concomitant tumor cell recruitment upon mobilization of PBPCs, particularly in stage IV breast cancer patients with bone marrow infiltration. The biologic and clinical significance of this finding is unknown at present.

Incidence of Tumor-Cell Contamination in Leukapheresis Products of Breast Cancer Patients Mobilized With Stem Cell Factor and Granulocyte Colony-Stimulating Factor (G-CSF) or With G-CSF Alone

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 340-347 ◽  
Author(s):  
Wilbur A. Franklin ◽  
John Glaspy ◽  
Sean M. Pflaumer ◽  
Roy B. Jones ◽  
Lisa Hami ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Clinical Stage ◽  
Stage Iv ◽  
Granulocyte Colony Stimulating Factor ◽  
Breast Cancer Patients ◽  
Stimulating Factor

We have assessed tumor contamination of peripheral blood progenitor cells (PBPC) in 203 high-risk breast cancer patients who were prospectively randomized to mobilization with stem cell factor (SCF) plus granulocyte colony-stimulating factor (G-CSF) versus G-CSF alone. The patients then received high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with PBPC support. One bone marrow aspirate obtained before treatment, one whole blood specimen obtained before cytokine infusion, and one to five leukapheresis products were tested for the presence of tumor cells by an alkaline phosphatase immunocytochemical technique with a targeted sensitivity of 1.7 tumor cells per 106 hematopoietic cells. Tumor cells were detected in the bone marrow, peripheral blood, and/or PBPC of 21 patients (10%). In 14 patients, bone marrow specimens were tumor-positive; in seven patients, premobilization whole blood specimens were tumor-positive, and in eight patients, leukapheresis products were tumor-positive. In five patients, repetitive or multiple specimens were tumor-positive, and in three cases, marrow, peripheral blood, and PBPC products were all tumor-positive. Nine of the patients in whom tumor cells were found in marrow or peripheral blood were clinical stage II to III and 12 were clinical stage IV. Nine of the tumor-positive patients were in the SCF + G-CSF arm and 12 were in the G-CSF arm. Tumor cells were detected in leukapheresis products of eight patients: three in the G-CSF + SCF arm and five in the G-CSF arm. We conclude that detectable tumor-cell contamination of bone marrow, peripheral blood, and/or PBPC occurred in approximately 10% of patients in this trial and was observed in stage II to III patients, as well as in stage IV patients. No significant difference could be found in the rate of PBPC tumor-cell contamination between patients who received SCF + G-CSF compared with those who received G-CSF alone. Neither mobilization regimen was found to increase the rate of tumor-cell contamination when control premobilization blood samples were compared with leukapheresis products.

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

Detection of circulating tumor cells in peripheral blood of heavily treated metastatic breast cancer patients

Breast Cancer ◽  
2011 ◽  
Vol 18 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Nahomi Tokudome ◽  
Yoshinori Ito ◽  
Shunji Takahashi ◽  
Kokoro Kobayashi ◽  
Shinichiro Taira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients

scholarly journals Liquid biopsy using the nanotube-CTC-chip: capture of invasive CTCs with high purity using preferential adherence in breast cancer patients

Lab on a Chip ◽  
2019 ◽  
Vol 19 (11) ◽  
pp. 1899-1915 ◽  
Author(s):  
Masoud S. Loeian ◽  
Sadegh Mehdi Aghaei ◽  
Farzaneh Farhadi ◽  
Veeresh Rai ◽  
Hong Wei Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
High Purity ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Breast Cancer Patients ◽  
Multiple Phenotypes

We report the development of the nanotube-CTC-chip for isolation of circulating tumor cells of multiple phenotypes from peripheral blood.

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