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British Journal of Cancer logoLink to British Journal of Cancer
. 1997;75(9):1368–1372. doi: 10.1038/bjc.1997.231

Collection of circulating progenitor cells after epirubicin, paclitaxel and filgrastim in patients with metastatic breast cancer.

P Pedrazzoli 1, C Perotti 1, G A Da Prada 1, F Bertolini 1, N Gibelli 1, L Torretta 1, M Battaglia 1, L Pavesi 1, P Preti 1, L Salvaneschi 1, G Robustelli della Cuna 1
PMCID: PMC2228223  PMID: 9155060

Abstract

The efficacy of high-dose chemotherapy (HDC) and circulating progenitor cell (CPC) transplantation in metastatic breast cancer (MBC) relies mainly on giving this treatment after a response to conventional induction chemotherapy has been achieved. For this reason an optimal mobilization regimen should be therapeutically effective while minimizing the number of leucaphereses required to support the myeloablative therapy. The combination of an anthracycline and paclitaxel in chemotherapy-untreated MBC has produced impressive response rates. We evaluated the CPC-mobilizing capacity of the combination epirubicin (90 mg m(-2)) and paclitaxel (135 mg m(-2)) followed by filgrastim (5 microg kg(-1) day(-1)) starting 48 h after chemotherapy administration in ten patients with MBC who were eligible for an HDC and CPC transplantation programme. Leucaphereses were performed by processing at least two blood volumes per procedure at recovery from neutrophil nadir when CD34+ cells in the peripheral blood exceeded 20 microl(-1). In most patients (six out of 10) more than 2.5 x 10(6) CD34+ cells kg(-1), a threshold considered to be sufficient for haematopoietic reconstitution, were collected with a single apheresis. In the remaining four patients an additional procedure, performed the following day, was enough to reach the required number of progenitors. These data suggest that the epirubicin-paclitaxel combination, besides being a very active regimen in MBC, is effective in releasing large amounts of progenitor cells into circulation.

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Selected References

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  1. Antman K., Ayash L., Elias A., Wheeler C., Hunt M., Eder J. P., Teicher B. A., Critchlow J., Bibbo J., Schnipper L. E. A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy. J Clin Oncol. 1992 Jan;10(1):102–110. doi: 10.1200/JCO.1992.10.1.102. [DOI] [PubMed] [Google Scholar]
  2. Bender J. G., To L. B., Williams S., Schwartzberg L. S. Defining a therapeutic dose of peripheral blood stem cells. J Hematother. 1992 Winter;1(4):329–341. doi: 10.1089/scd.1.1992.1.329. [DOI] [PubMed] [Google Scholar]
  3. Bensinger W., Appelbaum F., Rowley S., Storb R., Sanders J., Lilleby K., Gooley T., Demirer T., Schiffman K., Weaver C. Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol. 1995 Oct;13(10):2547–2555. doi: 10.1200/JCO.1995.13.10.2547. [DOI] [PubMed] [Google Scholar]
  4. Bensinger W., Singer J., Appelbaum F., Lilleby K., Longin K., Rowley S., Clarke E., Clift R., Hansen J., Shields T. Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor. Blood. 1993 Jun 1;81(11):3158–3163. [PubMed] [Google Scholar]
  5. Bezwoda W. R., Seymour L., Dansey R. D. High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial. J Clin Oncol. 1995 Oct;13(10):2483–2489. doi: 10.1200/JCO.1995.13.10.2483. [DOI] [PubMed] [Google Scholar]
  6. Bonadonna G., Gianni L., Santoro A., Bonfante V., Bidoli P., Casali P., Demicheli R., Valagussa P. Drugs ten years later: epirubicin. Ann Oncol. 1993 May;4(5):359–369. doi: 10.1093/oxfordjournals.annonc.a058514. [DOI] [PubMed] [Google Scholar]
  7. Breems D. A., van Hennik P. B., Kusadasi N., Boudewijn A., Cornelissen J. J., Sonneveld P., Ploemacher R. E. Individual stem cell quality in leukapheresis products is related to the number of mobilized stem cells. Blood. 1996 Jun 15;87(12):5370–5378. [PubMed] [Google Scholar]
  8. Brugger W., Bross K., Frisch J., Dern P., Weber B., Mertelsmann R., Kanz L. Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following polychemotherapy with etoposide, ifosfamide, and cisplatin. Blood. 1992 Mar 1;79(5):1193–1200. [PubMed] [Google Scholar]
  9. Buzdar A. U., Holmes F. A., Hortobagyi G. N. Paclitaxel in the treatment of metastatic breast cancer: M.D. Anderson Cancer Center experience. Semin Oncol. 1995 Jun;22(3 Suppl 6):101–104. [PubMed] [Google Scholar]
  10. Chao N. J., Schriber J. R., Grimes K., Long G. D., Negrin R. S., Raimondi C. M., Horning S. J., Brown S. L., Miller L., Blume K. G. Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy. Blood. 1993 Apr 15;81(8):2031–2035. [PubMed] [Google Scholar]
  11. Fennelly D., Schneider J., Spriggs D., Bengala C., Hakes T., Reich L., Barakat R., Curtin J., Moore M. A., Hoskins W. Dose escalation of paclitaxel with high-dose cyclophosphamide, with analysis of progenitor-cell mobilization and hematologic support of advanced ovarian cancer patients receiving rapidly sequenced high-dose carboplatin/cyclophosphamide courses. J Clin Oncol. 1995 May;13(5):1160–1166. doi: 10.1200/JCO.1995.13.5.1160. [DOI] [PubMed] [Google Scholar]
  12. Gianni A. M. Where do we stand with respect to the use of peripheral blood progenitor cells? Ann Oncol. 1994 Nov;5(9):781–784. doi: 10.1093/oxfordjournals.annonc.a059003. [DOI] [PubMed] [Google Scholar]
  13. Gianni L., Munzone E., Capri G., Fulfaro F., Tarenzi E., Villani F., Spreafico C., Laffranchi A., Caraceni A., Martini C. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol. 1995 Nov;13(11):2688–2699. doi: 10.1200/JCO.1995.13.11.2688. [DOI] [PubMed] [Google Scholar]
  14. Gianni L., Munzone E., Capri G., Villani F., Spreafico C., Tarenzi E., Fulfaro F., Caraceni A., Martini C., Laffranchi A. Paclitaxel in metastatic breast cancer: a trial of two doses by a 3-hour infusion in patients with disease recurrence after prior therapy with anthracyclines. J Natl Cancer Inst. 1995 Aug 2;87(15):1169–1175. doi: 10.1093/jnci/87.15.1169. [DOI] [PubMed] [Google Scholar]
  15. Holyoake T. L., Franklin I. M. Bone marrow transplants from peripheral blood. BMJ. 1994 Jul 2;309(6946):4–5. doi: 10.1136/bmj.309.6946.4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hortobagyi G. N., Holmes F. A., Theriault R. L., Buzdar A. U. Use of Taxol (paclitaxel) in breast cancer. Oncology. 1994 Oct;51 (Suppl 1):29–32. doi: 10.1159/000227413. [DOI] [PubMed] [Google Scholar]
  17. Hows J. M., Bradley B. A., Marsh J. C., Luft T., Coutinho L., Testa N. G., Dexter T. M. Growth of human umbilical-cord blood in longterm haemopoietic cultures. Lancet. 1992 Jul 11;340(8811):73–76. doi: 10.1016/0140-6736(92)90396-k. [DOI] [PubMed] [Google Scholar]
  18. Kennedy M. J. High-dose chemotherapy of breast cancer: is the question answered? J Clin Oncol. 1995 Oct;13(10):2477–2479. doi: 10.1200/JCO.1995.13.10.2477. [DOI] [PubMed] [Google Scholar]
  19. Peters W. P., Shpall E. J., Jones R. B., Olsen G. A., Bast R. C., Gockerman J. P., Moore J. O. High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer. J Clin Oncol. 1988 Sep;6(9):1368–1376. doi: 10.1200/JCO.1988.6.9.1368. [DOI] [PubMed] [Google Scholar]
  20. Pettengell R., Luft T., Henschler R., Hows J. M., Dexter T. M., Ryder D., Testa N. G. Direct comparison by limiting dilution analysis of long-term culture-initiating cells in human bone marrow, umbilical cord blood, and blood stem cells. Blood. 1994 Dec 1;84(11):3653–3659. [PubMed] [Google Scholar]
  21. Podda S., Ward M., Himelstein A., Richardson C., de la Flor-Weiss E., Smith L., Gottesman M., Pastan I., Bank A. Transfer and expression of the human multiple drug resistance gene into live mice. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9676–9680. doi: 10.1073/pnas.89.20.9676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ross A. A., Cooper B. W., Lazarus H. M., Mackay W., Moss T. J., Ciobanu N., Tallman M. S., Kennedy M. J., Davidson N. E., Sweet D. Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques. Blood. 1993 Nov 1;82(9):2605–2610. [PubMed] [Google Scholar]
  23. Schmitz N., Linch D. C., Dreger P., Goldstone A. H., Boogaerts M. A., Ferrant A., Demuynck H. M., Link H., Zander A., Barge A. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet. 1996 Feb 10;347(8998):353–357. doi: 10.1016/s0140-6736(96)90536-x. [DOI] [PubMed] [Google Scholar]
  24. Schwella N., Beyer J., Schwaner I., Heuft H. G., Rick O., Huhn D., Serke S., Siegert W. Impact of preleukapheresis cell counts on collection results and correlation of progenitor-cell dose with engraftment after high-dose chemotherapy in patients with germ cell cancer. J Clin Oncol. 1996 Apr;14(4):1114–1121. doi: 10.1200/JCO.1996.14.4.1114. [DOI] [PubMed] [Google Scholar]
  25. Seidman A. D. The emerging role of paclitaxel in breast cancer therapy. Clin Cancer Res. 1995 Mar;1(3):247–256. [PubMed] [Google Scholar]
  26. Sheridan W. P., Begley C. G., Juttner C. A., Szer J., To L. B., Maher D., McGrath K. M., Morstyn G., Fox R. M. Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet. 1992 Mar 14;339(8794):640–644. doi: 10.1016/0140-6736(92)90795-5. [DOI] [PubMed] [Google Scholar]
  27. Shimazaki C., Oku N., Ashihara E., Okawa K., Goto H., Inaba T., Ito K., Fujita N., Tsuji H., Murakami S. Collection of peripheral blood stem cells mobilized by high-dose Ara-C plus VP-16 or aclarubicin followed by recombinant human granulocyte-colony stimulating factor. Bone Marrow Transplant. 1992 Oct;10(4):341–346. [PubMed] [Google Scholar]
  28. Shpall E. J., Jones R. B., Bearman S. High-dose therapy with autologous bone marrow transplantation for the treatment of solid tumors. Curr Opin Oncol. 1994 Mar;6(2):135–138. doi: 10.1097/00001622-199403000-00004. [DOI] [PubMed] [Google Scholar]
  29. Siena S., Bregni M., Brando B., Belli N., Ravagnani F., Gandola L., Stern A. C., Lansdorp P. M., Bonadonna G., Gianni A. M. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Blood. 1991 Jan 15;77(2):400–409. [PubMed] [Google Scholar]
  30. Siena S., Bregni M., Brando B., Ravagnani F., Bonadonna G., Gianni A. M. Circulation of CD34+ hematopoietic stem cells in the peripheral blood of high-dose cyclophosphamide-treated patients: enhancement by intravenous recombinant human granulocyte-macrophage colony-stimulating factor. Blood. 1989 Nov 1;74(6):1905–1914. [PubMed] [Google Scholar]
  31. Siena S., Bregni M., Di Nicola M., Ravagani F., Peccatori F., Gandola L., Lombardi F., Tarella C., Bonadonna G., Gianni A. M. Durability of hematopoiesis following autografting with peripheral blood hematopoietic progenitors. Ann Oncol. 1994 Dec;5(10):935–941. doi: 10.1093/oxfordjournals.annonc.a058733. [DOI] [PubMed] [Google Scholar]
  32. Sledge G. W., Jr, Robert N., Sparano J. A., Cogleigh M., Goldstein L. J., Neuberg D., Rowinsky E., Baughman C., McCaskill-Stevens W. Eastern Cooperative Oncology Group studies of paclitaxel and doxorubicin in advanced breast cancer. Semin Oncol. 1995 Jun;22(3 Suppl 6):105–108. [PubMed] [Google Scholar]
  33. Torretta L., Perotti C., Dornini G., Danova M., Locatelli F., Pedrazzoli P., Preti P., Da Prada G. A., Pavesi L., Robustelli della Cuna G. Circulating progenitor cell collection: experience from 275 leukaphereses in various malignancies and in healthy donors. Haematologica. 1996 May-Jun;81(3):208–215. [PubMed] [Google Scholar]
  34. Tricot G., Jagannath S., Vesole D., Nelson J., Tindle S., Miller L., Cheson B., Crowley J., Barlogie B. Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients. Blood. 1995 Jan 15;85(2):588–596. [PubMed] [Google Scholar]
  35. Zimmerman T. M., Lee W. J., Bender J. G., Mick R., Williams S. F. Quantitative CD34 analysis may be used to guide peripheral blood stem cell harvests. Bone Marrow Transplant. 1995 Mar;15(3):439–444. [PubMed] [Google Scholar]

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