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Cell Procurement

Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization

Abstract

This was an open-label, single-center, phase II study of 20 patients with multiple myeloma who were either proven poor mobilizers (n=10; group A) or predicted poor mobilizers (n=10; group B) and were planned for autologous hematopoietic SCT. The aim was to assess the safety and efficacy of plerixafor for stem cell mobilization and tumor cell contamination. The peripheral blood (PB) CD34+ cell count was generally very low pre- plerixafor and increased significantly post-plerixafor administration. Cumulative apheresis yields of 2 × 106 CD34+ cells/kg were observed in 7 of 10 patients (group A) and 8 of 10 patients (group B). Among the proven poor mobilizers, there was no evidence of tumor cell mobilization in the PB after G-CSF plus plerixafor treatment. Seventeen of 20 (85%) patients underwent transplantation. Neutrophil engraftment occurred at a median of 13 days for all patients. Platelet engraftment occurred at a median of 16 days and 19 days for all proven and predicted poor mobilizers, respectively. At 12 months, 12 of 17 patients had documented durable grafts, 3 of 17 patients died and 2 of 17 patients were lost to follow-up; but they had documented graft durability at the previous 3- and 6-month visit. The safety profile of plerixafor in all patients was consistent with previous reports.

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References

  1. Attal M, Harousseau J-L, Stoppa A-M, Sotto J-J, Fuzibet J-G, Rossi J-F et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91–97.

    Article  CAS  Google Scholar 

  2. 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  Google Scholar 

  3. Fermand J-P, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55–65 years: long-term results of a randomized control trial from the group myelome-autogreffe. J Clin Oncol 2005; 23: 9227–9233.

    Article  CAS  Google Scholar 

  4. Craig JI, Langlands K, Parker AC, Anthony RS . Molecular detection of tumor contamination in peripheral blood stem cell harvests. Exp Hematol 1994; 22: 898–902.

    CAS  PubMed  Google Scholar 

  5. Gazitt Y, Reading CC, Hoffman R, Wickrema A, Vesole DH, Jagannath S et al. Purified CD34+ Lin− Thy+ stem cells do not contain clonal myeloma cells. Blood 1995; 86: 381–389.

    CAS  PubMed  Google Scholar 

  6. Dreyfus F, Ribrag V, Leblond V, Ravaud P, Melle J, Quarre MC et al. Detection of malignant B cells in peripheral blood stem cell collections after chemotherapy in patients with multiple myeloma. Bone Marrow Transplant 1995; 15: 707–711.

    CAS  PubMed  Google Scholar 

  7. Lemoli RM, Fortuna A, Motta MR, Rizzi S, Giudice V, Nannetti A et al. Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of multiple myeloma patients: positive selection and transplantation of enriched CD34+ cells to remove circulating tumor cells. Blood 1996; 87: 1625–1634.

    CAS  PubMed  Google Scholar 

  8. Boccadoro M, Omedé P, Dominietto A, Palumbo A, Bringhen S, Giaretta F et al. Multiple myeloma: the number of reinfused plasma cells does not influence outcome of patients treated with intensified chemotherapy and PBPC support. Bone Marrow Transplant 2000; 25: 25–29.

    Article  CAS  PubMed  Google Scholar 

  9. Lopez-Perez R, Garcia-Sanz R, Gonzalez D, Balanzategui A, Chillon MC, Alaejos I et al. Gene scanning of VDJH-amplified segments is a clinically relevant technique to detect contaminating tumor cells in the apheresis products of multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2001; 28: 665–672.

    Article  CAS  PubMed  Google Scholar 

  10. Galimberti S, Morabito F, Guerrini F, Palumbo GA, Azzara A, Martino M et al. Peripheral blood stem cell contamination evaluated by a highly sensitive molecular method fails to predict outcome of autotransplanted multiple myeloma patients. Br J Haematol 2003; 120: 405–412.

    Article  PubMed  Google Scholar 

  11. Vogel W, Kopp H, Kanz L, Einsele H . Myeloma cell contamination of peripheral blood stem-cell grafts can predict the outcome in multiple myeloma patients after high-dose chemotherapy and autologous stem-cell transplantation. J Cancer Res Clin Oncol 2005; 131: 214–218.

    Article  PubMed  Google Scholar 

  12. Gazitt Y, Tian E, Barlogie B, Reading CL, Vesole DH, Jagannath S et al. Differential mobilization of myeloma cells and normal hematopoietic stem cells in multiple myeloma after treatment with cyclophosphamide and granulocyte-macrophage colony-stimulating factor. Blood 1996; 87: 805–811.

    CAS  PubMed  Google Scholar 

  13. Flomenberg N, Devine S, Dipersio J, Liesveld J, McCarty J, Rowley S et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 2005; 106: 1867–1874.

    Article  CAS  PubMed  Google Scholar 

  14. Calandra G, McCarty J, McGuirk J, Tricot G, Crocker SA, Badel K et al. AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data. Bone Marrow Transplant 2007; 41: 331–338.

    Article  PubMed  Google Scholar 

  15. Barlogie B, Alexanian R, Pershouse M, Smallwood L, Smith L . Cytoplasmic immunoglobulin content in multiple myeloma. J Clin Invest 1985; 76: 765–769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gazitt Y, Freytes CO, Akay C, Badel K, Calandra G . Improved mobilization of peripheral blood CD34(+) cells and dendritic cells by AMD3100 plus granulocyte-colony-stimulating factor in non-Hodgkin's lymphoma patients. Stem Cells Dev 2007; 16: 657–666.

    Article  CAS  PubMed  Google Scholar 

  17. Andreeff M, Konoplev S, Wang R-Y, Zeng Z, McQueen T, Shi Y-X et al. Massive mobilization of AML cells into circulation by disruption of leukemia/stroma cell interactions using CXCR4 antagonist AMD3100: first evidence in patients and potential for abolishing bone marrow microenvironment-mediated resistance. Blood (ASH Annual Meeting Abstracts) 2006; 108: 568.

    Google Scholar 

  18. Anagnostopoulos A, Aleman A, Yang Y, Donato M, Weber D, Champlin R et al. Outcomes of autologous stem cell transplantation in patients with multiple myeloma who received dexamethasone-based nonmyelosuppressive induction therapy. Bone Marrow Transplant 2004; 33: 623–628.

    Article  CAS  PubMed  Google Scholar 

  19. Kopp HG, Yildirim S, Weisel KC, Kanz L, Vogel W . Contamination of autologous peripheral blood progenitor cell grafts predicts overall survival after high-dose chemotherapy in multiple myeloma. J Cancer Res Clin Oncol 2009; 135: 637–642.

    Article  CAS  PubMed  Google Scholar 

  20. Mateo G, Corral M, Almeida J, Lopez-Berges C, Nieto J, Garcia-Marcos A et al. Immunophenotypic analysis of peripheral blood stem cell harvests from patients with multiple myeloma. Haematologica 2003; 88: 1013–1021.

    PubMed  Google Scholar 

  21. Franklin WA, Glaspy J, Pflaumer SM, Jones RB, Hami L, Martinez C et al. Incidence of tumor-cell contamination in leukapheresis products of breast cancer patients mobilized with stem cell factor and granulocyte colony-stimulating factor (G-CSF) or with G-CSF alone. Blood 1999; 94: 340–347.

    CAS  PubMed  Google Scholar 

  22. Desikan KR, Jagannath S, Siegel D, Nelson J, Bracy D, Barlogie B et al. Collection of more hematopoietic progenitor cells with large volume leukapheresis in patients with multiple myeloma. Leuk Lymphoma 1998; 28: 501–508.

    Article  CAS  PubMed  Google Scholar 

  23. Knudsen LM, Rasmussen T, Nikolaisen K, Johnsen HE . Mobilisation of tumour cells along with CD34+ cells to peripheral blood in multiple myeloma. Eur J Haematol 2001; 67: 289–295.

    Article  CAS  PubMed  Google Scholar 

  24. Kiel K, Cremer FW, Ehrbrecht E, Wallmeier M, Hegenbart U, Goldschmidt H et al. First and second apheresis in patients with multiple myeloma: no differences in tumor load and hematopoietic stem cell yield. Bone Marrow Transplant 1998; 21: 1109–1115.

    Article  CAS  PubMed  Google Scholar 

  25. Cremer FW, Kiel K, Wallmeier M, Haas R, Goldschmidt H, Moos M . Leukapheresis products in multiple myeloma: lower tumor load after mobilization with cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) compared with G-CSF alone. Exp Hematol 1998; 26: 969–975.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The study was conducted at the University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. TG designed the study, recruited the patients, gathered and interpreted the data, and prepared the paper; MC designed the study, recruited the patients, gathered and interpreted the data, and prepared the paper; GC designed the study, interpreted the data, and prepared the paper.

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Correspondence to G Tricot.

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Tricot, G., Cottler-Fox, M. & Calandra, G. Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization. Bone Marrow Transplant 45, 63–68 (2010). https://doi.org/10.1038/bmt.2009.130

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