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Mobilization of peripheral blood progenitor cells with a combination of cyclophosphamide, r-metHuSCF and filgrastim in patients with breast cancer previously treated with chemotherapy

Abstract

The objective of our study was to determine the effect of adding r-metHuSCF to Filgrastim and cyclophosphamide for mobilization of peripheral blood progenitor cells (PBPC), on collection of CD34+ cells and engraftment after autologous stem cell transplant. Twenty-three patients with previously treated stage II–IV breast cancer received cyclophosphamide (3 g/m2), Filgrastim 5 μg/kg daily and r-metHuSCF 20 μg/kg daily. Two PBPC collections were performed on consecutive days starting the day the WBC count was above 7.5 × 103/μl. Collection was performed between days +9 and +12 and the median number of CD34+ cells collected was 9.9 × 106/kg (1.1–53.1) and 6.6 × 106/kg (1.4–33.8) for the first and second apheresis, respectively. Despite being previously treated patients, the target CD34+ cell dose required for SCT was obtained in all patients. SCT was associated with rapid neutrophil and platelet engraftment and a highly significant correlation was observed between the number of CD34+ cells infused and engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate local skin rash being the most frequently reported adverse event. In conclusion, addition of r-metHuSCF induces mobilization of a large number of CD34+ cells which results in shortening of time to engraftment and hospitalization.

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References

  1. Siena S, Bregni M, Brando B, Ravagnani F, Bonadonna G, Gianni AM . 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; 74: 1905–1914.

    CAS  PubMed  Google Scholar 

  2. Gratwohl A, Passweg J, Baldomero H, Hermans J . Blood and marrow transplantation activity in Europe 1997. European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 1999; 24: 231–245.

    Article  CAS  Google Scholar 

  3. To LB, Haylock DN, Simmons PJ, Juttner CA . The biology and clinical uses of blood stem cells. Blood 1997; 89: 2233–2258.

    CAS  PubMed  Google Scholar 

  4. Gianni AM, Siena S, Bregni M, Tarella C, Stern AC, Pileri A, Bonadonna G . Granulocyte–macrophage colony stimulating factor to harvest circulating hematopoietic stem cells for autotransplantation. Lancet 1989; 2: 580–585.

    Article  CAS  Google Scholar 

  5. 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; 13: 2547–2555.

    Article  CAS  Google Scholar 

  6. Ketterer N, Salles G, Moullet I, Dumontet C, ElJaafari-Corbin A, Tremisi P, Thieblemont C, Durand B, Neidhardt-Berard EM, Samaha H, Rigal D, Coiffier B . Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies. Br J Haematol 1998; 103: 235–242.

    Article  CAS  Google Scholar 

  7. Sudo Y, Shimazaki C, Ashihara E, Kikuta T, Hirai H, Sumikuma T, Yamagata N, Goto H, Inaba T, Fujita N, Nakagawa M . Synergistic effect of FLT-3 ligand on the granulocyte colony-stimulating factor induced mobilization of hematopoietic stem cells and progenitor cells into blood of mice. Blood 1997; 89: 3186–3191.

    CAS  PubMed  Google Scholar 

  8. Brasel K, McKenna HJ, Morrisey PJ, Charrier K, Morris AE, Lee CC, Williams DE, Lyman SD . Hematological effects of flt3 ligand in vivo in mice. Blood 1996; 88: 2004–2012.

    CAS  PubMed  Google Scholar 

  9. Begley CG, Basser R, Mansfield R, Thomson B, Parker WRL, Layton J, To B, Cebon J, Sheridan WP, Fox RM, Green MD . Enhanced levels and enhanced clonogenic capacity of blood progenitor cells following administration of stem cell factor plus granulocyte colony-stimulating growth factor to humans. Blood 1997; 90: 3378–3389.

    CAS  PubMed  Google Scholar 

  10. Moskowitz CH, Stiff P, Gordon MS, McNiece I, Ho AD, Costa JJ, Broun ER, Bayer RA, Wyres M, Hill J, Jelaca-Maxwell K, Nichols CR, Brown SL, Nimer SD, Gabrilove J . Recombinant methionyl human stem cell factor and filgrastim for peripheral blood progenitor cell mobilization and transplantation in non-Hodgkin’s lymphoma patients – results of a phase I/II trial. Blood 1997; 89: 3136–3147.

    CAS  PubMed  Google Scholar 

  11. Facon T, Harousseau JL, Maloisel F, Attal M, Odriozola J, Alegre A, Schroyens W, Hulin C, Schots R, Marin P, Guilhot F, Granena A, De Waele M, Pigneux A, Meresse V, Clark P, Reiffers J . Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial. Blood 1999; 94: 1218–1225.

    CAS  PubMed  Google Scholar 

  12. Basser RL, To LB, Begley CG, Maher D, Juttner C, Cebon J, Mansfield R, Olver I, Duggan G, Szer J, Collins J, Schwartz B, Marty J, Menchaca D, Sheridan WP, Fox RM, Green MD . Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell factor. J Clin Oncol 1998; 16: 1899–1908.

    Article  CAS  Google Scholar 

  13. Weaver A, Ryder D, Crowther D, Dexter TM, Testa NG . Increased numbers of long-term culture-initiating cells in the apheresis product of patients randomized to receive increasing doses of stem cell factor administered in combination with chemotherapy and a standar dose of granulocyte colony-stimulating factor. Blood 1996; 88: 3323–3328.

    CAS  PubMed  Google Scholar 

  14. Shpall EJ, Wheeler CA, Turner SA, Yanovich S, Brown RA, Pecora AL, Shea TC, Mangan KF, Williams SF, LeMaistre CF, Long GD, Jones R, Davis MW, Murphy-Filkins R, Parker WR, Glaspy JA . A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high-risk breast cancer patients. Blood 1999; 93: 2491–2501.

    CAS  PubMed  Google Scholar 

  15. Gratama JW, Menendez P, Kraan J, Orfao A . Loss of CD34(+) hematopoietic progenitor cells due to washing can be reduced by the use of fixative-free erythrocyte lysing reagents. J Immunol Methods 2000; 239: 13–23.

    Article  CAS  Google Scholar 

  16. Menendez P, Prosper F, Bueno C, Arbona C, San Miguel JF, Garcia-Conde J, Sola C, Hornedo J, Cortes-Funes H, Orfao A . Sequential analysis of CD34+ and CD34− cell subsets in peripheral blood and leukapheresis products from breast cancer patients mobilized with SCF plus G-CSF and cyclophosphamide. Leukemia 2001; 15: 430–439.

    Article  CAS  Google Scholar 

  17. Glaspy JA, Shpall EJ, LeMaistre CF, Bridell RA, Menchaca DM, Turner SA, Lill M, Chap L, Jones R, Wiers MD, Sheridan WP, McNiece IK . Peripheral blood progenitor cell mobilization using stem cell factor in combination with filgrastim in breast cancer patients. Blood 1997; 90: 2939–2951.

    CAS  PubMed  Google Scholar 

  18. Weaver A, Chang J, Wrigley E, de Wynter E, Woll PJ, Lind M, Jenkins B, Gill C, Wilkinson PM, Pettengell R, Radford JA, Collins CD, Dexter TM, Testa NG, Crowther D . Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer. J Clin Oncol 1998; 16: 2601–2612.

    Article  CAS  Google Scholar 

  19. 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; 85: 588–596.

    CAS  PubMed  Google Scholar 

  20. Dreger P, Klöss M, Petersen B, Haferlach T, Löeffler H, Lëffler M, Schmitz N . Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts. Blood 1995; 86: 3970–3978.

    CAS  PubMed  Google Scholar 

  21. To LB, Dyson PG, Juttner CA . Cell dose effect in circulating stem cell autografting. Lancet 1986; 2: 404–405.

    Article  CAS  Google Scholar 

  22. Siena S, Bregni M, Brando B, Belli N, Ravagnani F, Gandola L, Stern AC, Lansdorp PM, Bonadonna G, Gianni AM . Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Blood 1991; 77: 400–409.

    CAS  PubMed  Google Scholar 

  23. Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L, West W . An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood 1995; 86: 3961–3969.

    CAS  PubMed  Google Scholar 

  24. Curti A, Fogli M, Ratta M, Tura S, Lemoli RM . Stem cell factor and FLT3-ligand are strictly required to sustain the long-term expansion of primitive CD34(+)DR(−) dendritic cell precursors. J Immunol 2001; 166: 848–854.

    Article  CAS  Google Scholar 

  25. Ferlazzo G, Klein J, Paliard X, Wei WZ, Galy A . Dendritic cells generated from CD34+ progenitor cells with flt3 ligand, c-kit ligand, GM-CSF, IL-4, and TNF-alpha are functional antigen-presenting cells resembling mature monocyte-derived dendritic cells. J Immunother 2000; 23: 48–58.

    Article  CAS  Google Scholar 

  26. Saraya K, Reid CD . Stem cell factor and the regulation of dendritic cell production from CD34+ progenitors in bone marrow and cord blood. Br J Haematol 1996; 93: 258–264.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by AMGEN SA, Spain.

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Prósper, F., Solá, C., Hornedo, J. et al. Mobilization of peripheral blood progenitor cells with a combination of cyclophosphamide, r-metHuSCF and filgrastim in patients with breast cancer previously treated with chemotherapy. Leukemia 17, 437–441 (2003). https://doi.org/10.1038/sj.leu.2402750

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