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Mobilization of tumor cells and hematopoietic progenitor cells into
peripheral blood of patients with solid tumors [see comments]
W Brugger, KJ Bross, M Glatt, F Weber, R Mertelsmann and L Kanz
Department of Hematology/Oncology, Albert-Ludwigs University Medical
Center, Freiburg, Germany.
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.
Volume 83,
Issue 3,
pp. 636-640,
02/01/1994
Copyright © 1994 by The American Society of Hematology
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