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[Cancer Research 54, 2366-2371, May 1, 1994]
© 1994 American Association for Cancer Research

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Bone Marrow Micrometastases in Chemotherapy-responsive Advanced Breast Cancer: Effect of ex Vivo Purging with 4-Hydroperoxycyclophosphamide1

Jose Passos-Coelho, Amy A. Ross, Janice M. Davis, Anne-Marie Huelskamp, Barbara Clarke, Stephen J. Noga, Nancy E. Davidson and M. John Kennedy2

Johns Hopkins Oncology Center, Baltimore, Maryland 21287 [J. P. C., J. M. D., A. M. H., B. C., S. J. N., N. E. D., M. J. K.], and BIS Laboratories Reseda, California 91335 [A. A. R.]

Tumor contamination of hematopoietic stem cell grafts may influence the outcome of breast cancer patients treated with high-dose chemotherapy. The goals of this study were: (a) to evaluate the prevalence of tumor contamination of bone marrow (BM) harvests in patients responding to systemic chemotherapy; (b) to evaluate reduction of BM tumor contamination by ex vivo purging with 4-hydroperoxycyclophosphamide (4HC); and (c) to compare the tumor contamination of peripheral blood progenitor cell collections and BM in advanced-stage breast cancer patients designated for peripheral blood progenitor cell influsion. We evaluated pre- and post-4HC purge BM specimens from 20 patients for tumor contamination using immunocytochemistry and for in vitro growth potential of tumor cells using a tumor cell clonogenic assay. Pre-4HC purge BM specimens from 15 of 20 (75%) patients were immunocytochemistry and tumor cell clonogenic assay negative. The remaining 5 BM specimens were immunocytochemistry positive, but only 3 of 5 specimens were tumor cell clonogenic assay positive. In vitro tumor colony growth was not observed in any post-4HC purge BM specimens. We also evaluated nine patients with bone or BM metastases from the start of induction chemotherapy. We found less tumor involvement of peripheral blood progenitor cell collections than of simultaneously obtained bone marrow aspirates. We conclude that bone marrow micrometastases occur with low frequency in women with chemotherapy-sensitive breast cancer and that ex vivo purging with 4HC may render tumor cells nonviable.

1 Supported in part by American Cancer Society Grant RD-353 and NIH Grants CA-58340 and CA-57158. M. J. K. is the recipient of an American Cancer Society Clinical Oncology Career Development Award.

2 To whom requests for reprints should be addressed, at Oncology 137, Johns Hopkins Oncology Center, 600 North Wolfe Street, Baltimore, MD 21287.

Received 7/ 7/93. Accepted 3/ 2/94.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Molecular Cancer Research Cancer Prevention Research
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Copyright © 1994 by the American Association for Cancer Research.