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Stem Cell Procurement

High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma

Abstract

Novel agents are increasingly used during induction therapy for multiple myeloma (MM), but there is concern about their potential impact on stem cell mobilization. Regimens containing either thalidomide or cyclophosphamide have little or no impact on stem cell collection. In this retrospective review of 136 patients with newly diagnosed MM, we show that the combination of thalidomide and oral CY with dexamethasone (CTD) during induction therapy impaired stem cell mobilization substantially. Compared with VAD (vincristine, doxorubicin, dexamethasone) and a VAD-like induction regimen, the stem cell collection yield after CTD was decreased by 49% (median 5.0 vs 9.8 × 106 CD34+cells/kg, P<0.001). Following CTD, more patients failed to mobilize enough stem cells for one (25.4 vs 5.8%, P=0.002) or two (39.4 vs 15.9%, P=0.002) transplants. These results demonstrate that the combination of thalidomide and oral CY impairs stem cell mobilization and indicate that drugs with no previously reported relevant effect on stem cell mobilization can have a substantial impact when given in combination.

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References

  1. Kumar S . Stem cell transplantation for multiple myeloma. Curr Opin Oncol 2009; 21: 162–170.

    Article  CAS  PubMed  PubMed Central  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  Google Scholar 

  3. Boccadoro M, Palumbo A, Bringhen S, Merletti F, Ciccone G, Richiardi L et al. Oral melphalan at diagnosis hampers adequate collection of peripheral blood progenitor cells in multiple myeloma. Haematologica 2002; 87: 846–850.

    CAS  PubMed  Google Scholar 

  4. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC . Multiple myeloma. Lancet 2009; 374: 324–339.

    Article  PubMed  Google Scholar 

  5. Kumar S, Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W et al. Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide, lenalidomide or bortezomib- containing regimens. Blood 2009; 114: 1729–1735.

    Article  CAS  PubMed  Google Scholar 

  6. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Gastineau DA et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 2007; 21: 2035–2042.

    Article  CAS  Google Scholar 

  7. Paripati H, Stewart AK, Cabou S, Dueck A, Zepeda VJ, Pirooz N et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia 2008; 22: 1282–1284.

    Article  CAS  Google Scholar 

  8. Mazumder A, Kaufman J, Niesvizky R, Lonial S, Vesole D, Jagannath S . Effect of lenalidomide therapy on mobilization of peripheral blood stem cells in previously untreated multiple myeloma patients. Leukemia 2008; 22: 1280–1281. author reply 1281–1282.

    Article  CAS  Google Scholar 

  9. Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 2005; 106: 35–39.

    Article  CAS  Google Scholar 

  10. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR . Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006; 24: 431–436.

    Article  CAS  Google Scholar 

  11. Breitkreutz I, Lokhorst HM, Raab MS, Holt B, Cremer FW, Herrmann D et al. Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield. Leukemia 2007; 21: 1294–1299.

    Article  CAS  PubMed  Google Scholar 

  12. Ghobrial IM, Dispenzieri A, Bundy KL, Gastineau DA, Rajkumar SV, Therneau TM et al. Effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma. Bone Marrow Transplant 2003; 32: 587–592.

    Article  CAS  PubMed  Google Scholar 

  13. Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 2009; 23: 1337–1341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. de la Rubia J, Blade J, Lahuerta JJ, Ribera JM, Martinez R, Alegre A et al. Effect of chemotherapy with alkylating agents on the yield of CD34+ cells in patients with multiple myeloma Results of the Spanish Myeloma Group (GEM) Study. Haematologica 2006; 91: 621–627.

    CAS  PubMed  Google Scholar 

  15. Mellqvist UH, Lenhoff S, Johnsen HE, Hjorth M, Holmberg E, Juliusson G et al. Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of a randomized comparison with vincristine, doxorubicin, and dexamethasone. Cancer 2008; 112: 129–135.

    Article  CAS  Google Scholar 

  16. Cook G, Clark RE, Morris TC, Robertson M, Lucie NP, Anderson S et al. A randomized study (WOS MM1) comparing the oral regime Z-Dex (idarubicin and dexamethasone) with vincristine, adriamycin and dexamethasone as induction therapy for newly diagnosed patients with multiple myeloma. Br J Haematol 2004; 126: 792–798.

    Article  CAS  PubMed  Google Scholar 

  17. Popat U, Saliba R, Thandi R, Hosing C, Qazilbash M, Anderlini P et al. Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant 2009; 15: 718–723.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Levesque JP, Winkler IG . Mobilization of hematopoietic stem cells: state of the art. Curr Opin Organ Transplant 2008; 13: 53–58.

    Article  PubMed  Google Scholar 

  19. Gratwohl A, Baldomero H, Schwendener A, Rocha V, Apperley J, Frauendorfer K et al. The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel cellular therapies. Bone Marrow Transplant 2009; 43: 275–291.

    Article  CAS  Google Scholar 

  20. Gratwohl A, Baldomero H, Frauendorfer K, Urbano-Ispizua A . EBMT activity survey 2004 and changes in disease indication over the past 15 years. Bone Marrow Transplant 2006; 37: 1069–1085.

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank the apheresis nurses and the team at the John Goldman Centre for Cellular Therapy for patient care and processing of the stem cell products. We are grateful for support from the National Institute for Health Research Biomedical Research Centre funding scheme.

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Correspondence to A Rahemtulla.

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Auner, H., Mazzarella, L., Cook, L. et al. High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma. Bone Marrow Transplant 46, 364–367 (2011). https://doi.org/10.1038/bmt.2010.141

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