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Cell Procurement

EPO in combination with G-CSF improves mobilization effectiveness after chemotherapy with ifosfamide, epirubicin and etoposide and reduces costs during mobilization and transplantation of autologous hematopoietic progenitor cells

Bone Marrow Transplantation volume 43, pages 197–206 (2009)Cite this article

Abstract

A successful stem cell harvest is a prerequisite for peripheral blood SCT. We investigated the number of CD34+ cells mobilized, the number of leukaphereses needed and the expenses of treatment for 28 patients with multiple myeloma randomly assigned to receive either G-CSF alone or G-CSF+EPO for stem cell mobilization after chemotherapy with ifosfamide, epirubicin and etoposide. All patients treated with G-CSF+EPO reached the threshold of 6 × 106 CD34+ cells per kg body weight (kgbw), with a mean of 1.3 leukaphereses. On average 15.4 × 106 CD34+ cells/kgbw were collected. In the G-CSF-alone group, the mean number of leukaphereses was 1.8, and 12.6 × 106 CD34+ cells/kgbw were collected, and two patients failed the threshold. Overall costs per patient for mobilization and leukaphereses were €8339 (G-CSF+EPO) and €8842 (G-CSF). After transplantation, fewer blood transfusions (0.6 versus 1.3, P=0.05), fewer days on antibiotics (2.3 versus 6.1, P=0.02) and a shorter hospital stay (15.2 versus 17.8, P=0.06) were noted in the G-CSF+EPO group resulting in a 19.2% reduction of costs for each transplant (P=0.018). In summary, EPO improves the mobilization efficiency of G-CSF and so reduces costs of mobilization and SCT.

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References

  1. Copelan EA . Hematopoietic stem-cell transplantation. N Engl J Med 2006; 354: 1813–1826.

    Article  CAS  PubMed  Google Scholar 

  2. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495–2502.

    Article  CAS  PubMed  Google Scholar 

  3. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

    Article  CAS  PubMed  Google Scholar 

  4. Kyle RA, Rajkumar SV . Multiple myeloma. N Engl J Med 2004; 351: 1860–1873.

    Article  CAS  PubMed  Google Scholar 

  5. Kaushansky K . Lineage-specific hematopoietic growth factors. N Engl J Med 2006; 354: 2034–2045.

    Article  CAS  PubMed  Google Scholar 

  6. Meisenberg B, Brehm T, Schmeckel A, Miller W, McMillan R . A combination of low-dose cyclophosphamide and colony-stimulating factors is more cost-effective than granulocyte-colony-stimulating factors alone in mobilizing peripheral blood stem and progenitor cells. Transfusion 1998; 38: 209–215.

    Article  CAS  PubMed  Google Scholar 

  7. Narayanasami U, Kanteti R, Morelli J, Klekar A, Al Olama A, Keating C et al. Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of hematopoietic progenitor cells for rescue in autologous transplantation. Blood 2001; 98: 2059–2064.

    Article  CAS  PubMed  Google Scholar 

  8. Pecora AL . Impact of stem cell dose on hematopoietic recovery in autologous blood stem cell recipients. Bone Marrow Transplant 1999; 23 (Suppl 2): S7–S12.

    Article  PubMed  Google Scholar 

  9. Shpall EJ . The utilization of cytokines in stem cell mobilization strategies. Bone Marrow Transplant 1999; 23 (Suppl 2): S13–S19.

    Article  PubMed  Google Scholar 

  10. Pierelli L, Perillo A, Greggi S, Salerno G, Panici PB, Menichella G et al. Erythropoietin addition to granulocyte colony-stimulating factor abrogates life-threatening neutropenia and increases peripheral-blood progenitor-cell mobilization after epirubicin, paclitaxel, and cisplatin combination chemotherapy: results of a randomized comparison. J Clin Oncol 1999; 17: 1288–1295.

    Article  CAS  PubMed  Google Scholar 

  11. Olivieri A, Offidani M, Cantori I, Ciniero L, Ombrosi L, Masia MC et al. Addition of erythropoietin to granulocyte colony-stimulating factor after priming chemotherapy enhances hemopoietic progenitor mobilization. Bone Marrow Transplant 1995; 16: 765–770.

    CAS  PubMed  Google Scholar 

  12. Pierelli L, Menichella G, Scambia G, Teofili L, Iovino S, Serafini R et al. In vitro and in vivo effects of recombinant human erythropoietin plus recombinant human G-CSF on human haemopoietic progenitor cells. Bone Marrow Transplant 1994; 14: 23–30.

    CAS  PubMed  Google Scholar 

  13. Durie BGM, Salmon SE . A clinical staging system for multiple myeloma: correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975; 36: 842–854.

    Article  CAS  PubMed  Google Scholar 

  14. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649–655.

    Article  CAS  PubMed  Google Scholar 

  15. Grassinger J, Mueller G, Hart C, Nilsson SK, Haylock DN, Andreesen R et al. Detection and quantification of functionally defined hematopoietic progenitor cells and tissue specific mRNA within the peripheral blood of myeloma patients after administration of granulocyte colony-stimulating (G-CSF) factor and erythropoietin (EPO). Eur J Haematol 2008; 80: 20–30.

    CAS  PubMed  Google Scholar 

  16. Koc ON, Gerson SL, Cooper BW, Laughlin M, Meyerson H, Kutteh L et al. Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF. J Clin Oncol 2000; 18: 1824–1830.

    Article  CAS  PubMed  Google Scholar 

  17. Hart C, Blank C, Krause SW, Andreesen R, Hennemann B . Ifosfamide, epirubicin, and etoposide (IEV) mobilize peripheral blood stem cells more efficiently than cyclophosphamide/etoposide. Ann Hematol 2007; 86: 575–581.

    Article  CAS  PubMed  Google Scholar 

  18. Stiff PJ . Management strategies for the hard-to-mobilize patient. Bone Marrow Transplant 1999; 23 (Suppl 2): S29–S33.

    Article  PubMed  Google Scholar 

  19. Waller CF, von Lintig F, Daskalakis A, Musahl V, Lange W . Mobilization of peripheral blood progenitor cells in patients with breast cancer: a prospective randomized trial comparing rhG-CSF with the combination of rhG-CSF plus rhEpo after VIP-E chemotherapy. Bone Marrow Transplant 1999; 24: 19–24.

    Article  CAS  PubMed  Google Scholar 

  20. Perillo A, Ferrandina G, Pierelli L, Rutella S, Mancuso S, Scambia G . Cytokines alone for PBPC collection in patients with advanced gynaecological malignancies: G-CSF vs G-CSF plus EPO. Bone Marrow Transplant 2004; 34: 743–744.

    Article  CAS  PubMed  Google Scholar 

  21. Kokhaei P, Abdalla AO, Hansson L, Mikaelsson E, Kubbies M, Haselbeck A et al. Expression of erythropoietin receptor and in vitro functional effects of epoetins in B-cell malignancies. Clin Cancer Res 2007; 13: 3536–3544.

    Article  CAS  PubMed  Google Scholar 

  22. Katz O, Gil L, Lifshitz L, Prutchi-Sagiv S, Gassmann M, Mittelman M et al. Erythropoietin enhances immune responses in mice. Eur J Immunol 2007; 37: 1584–1593.

    Article  CAS  PubMed  Google Scholar 

  23. Mann RA, Jetzt AE, Singh M, Singh AB . The effect of erythropoietin administration on murine bone marrow chimeras. Immunol Lett 1996; 49: 15–20.

    Article  CAS  PubMed  Google Scholar 

  24. Hassan K, Shternberg L, Alhaj M, Giron R, Reshef R, Barak M et al. The effect of erythropoietin therapy and hemoglobin levels on the immune response to Engerix-B vaccination in chronic kidney disease. Ren Fail 2003; 25: 471–478.

    Article  CAS  PubMed  Google Scholar 

  25. Levesque JP, Hendy J, Takamatsu Y, Williams B, Winkler IG, Simmons PJ . Mobilization by either cyclophosphamide or granulocyte colony-stimulating factor transforms the bone marrow into a highly proteolytic environment. Exp Hematol 2002; 30: 440–449.

    Article  CAS  PubMed  Google Scholar 

  26. Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ . Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood 2001; 98: 1289–1297.

    Article  CAS  PubMed  Google Scholar 

  27. Semerad CL, Christopher MJ, Liu F, Short B, Simmons PJ, Winkler I et al. G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood 2005; 106: 3020–3027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Levesque JP, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ . Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest 2003; 111: 187–196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antogonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol 2004; 22: 1095–1102.

    Article  CAS  PubMed  Google Scholar 

  30. Abraham M, Biyder K, Begin M, Wald H, Weiss ID, Galun E et al. Enhanced unique pattern of hematopoietic cell mobilization induced by the CXCR4 antagonist 4F-benzoyl-TN14003. Stem Cells 2007; 25: 2158–2166.

    Article  CAS  PubMed  Google Scholar 

  31. Klaesson S, Ringden O, Ljungman P, Lonnqvist B, Wennberg L . Reduced blood transfusions requirements after allogeneic bone marrow transplantation: results of a randomised, double-blind study with high-dose erythropoietin. Bone Marrow Transplant 1994; 13: 397–402.

    CAS  PubMed  Google Scholar 

  32. Vannucchi AM, Bosi A, Linari S, Guidi S, Longo G, Lombardini L et al. High doses of recombinant human erythropoietin fail to accelerate platelet reconstitution in allogeneic bone marrow transplantation. Results of a pilot study. Haematologica 1997; 82: 53–56.

    CAS  PubMed  Google Scholar 

  33. Hogge DE, Lambie K, Sutherland HJ, Benny WB, Dalal B, Currie C et al. Quantitation of primitive and lineage-committed progenitors in mobilized peripheral blood for prediction of platelet recovery post autologous transplant. Bone Marrow Transplant 2000; 25: 589–598.

    Article  CAS  PubMed  Google Scholar 

  34. Moeremans K, Annemans L . An update: health economics of managing multiple myeloma. Eur J Cancer 2006; 42: 1684–1691.

    Article  CAS  PubMed  Google Scholar 

  35. Chabannon C, Le Corroller AG, Viret F, Eillen C, Faucher C, Moatti JP et al. Cost-effectiveness of repeated aphereses in poor mobilizers undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation. Leukemia 2003; 17: 811–813.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Hematology and Oncology, Regensburg University Medical Center, Regensburg, Germany

    C Hart, J Grassinger, R Andreesen & B Hennemann

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Correspondence to B Hennemann.

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Hart, C., Grassinger, J., Andreesen, R. et al. EPO in combination with G-CSF improves mobilization effectiveness after chemotherapy with ifosfamide, epirubicin and etoposide and reduces costs during mobilization and transplantation of autologous hematopoietic progenitor cells. Bone Marrow Transplant 43, 197–206 (2009). https://doi.org/10.1038/bmt.2008.315

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