Annals of Hematology

, Volume 85, Issue 6, pp 394–399

Vinorelbine plus intermediate dose cyclophosphamide is an effective and safe regimen for the mobilization of peripheral blood stem cells in patients with multiple myeloma

  • Mario Annunziata
  • Maria Celentano
  • Barbara Pocali
  • Maria Rosaria D’Amico
  • Salvatore Palmieri
  • Assunta Viola
  • Carolina Copia
  • Claudio Falco
  • Luigi Del Vecchio
  • Felicetto Ferrara
Original Article


High dose cyclophosphamide (HD-Cy) is commonly used to mobilize stem cells in multiple myeloma (MM). However, timing of collection is variable and incidence of side effects is substantial. We evaluated a combination of vinorelbine (VNB) (25 mg/m2 day 1) plus Cy (1.5 g/m2 day 2) and G-CSF as mobilizing regimen in 37 patients with MM. Results were compared to those achieved in 41 previously diagnosed patients mobilized with Cy at 4 g/m2. Overall, 36/37 patients receiving VNB–Cy (97%) mobilized, as opposed to 40/41 (97%) in the controls (p:0.51). Median CD34+ cells peak was 94/μl for VNB–Cy patients and 96 for controls, p=0.36; median number of CD34+ cells collected was 9.2×106/kg and 8.7×106/kg, respectively (p=0.85). Median number of days to the highest CD34 count was shorter for VNB–Cy patients (nine vs 11, p=0.001). No VNB–Cy patient experienced grade 3–4 neutropenia and thrombocytopenia, as opposed to 63 and 19% in the controls (p=0.001 and 0.01, respectively). Hospitalization from toxicity was never required in VNB–Cy patients as compared to 19% in control group (p=0.01). We conclude that an outpatient combination of VNB plus intermediate dose Cy plus G-CSF is a safe, predictable, and highly effective mobilization regimen for patients with newly-diagnosed MM.


Stem cell Mobilization Multiple myeloma Vinorelbine Cyclophosphamide 


  1. 1.
    Aapro MS, Harper P, Johnson SA, Vermorken JB (2001) Developments in cytotoxic chemotherapy: advances in treatment utilising vinorelbine. Crit Rev Oncol Hematol 40:251–263PubMedCrossRefGoogle Scholar
  2. 2.
    Alexanian R, Weber D, Giralt S, Dimopoulos M, Delasalle K, Smith T, Champlin R (2001) Impact of complete remission with intensive therapy in patients with responsive multiple myeloma. Bone Marrow Transplant 27:1037–1043PubMedCrossRefGoogle Scholar
  3. 3.
    Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. New Engl J Med 335:91–97PubMedCrossRefGoogle Scholar
  4. 4.
    Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R for the InterGroupe Francophone du Myelome (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. New Engl J Med 349:2495–2502PubMedCrossRefGoogle Scholar
  5. 5.
    Badros A, Barlogie B, Siegel E, Morris C, Desikan R, Zangari M, Fassas A, Anaissie E, Munshi N, Tricot G (2001) Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol 114:600–607PubMedCrossRefGoogle Scholar
  6. 6.
    Ballestrero A, Montemurro F, Gonella R, Capaldi A, Danova M, Friedman D, Puglisi M, Aglietta M, Patrone F (2003) Dose-dense vinorelbine and paclitaxel with granulocyte colony-stimulating factor in metastatic breast cancer patients: anti-tumor activity and peripheral blood progenitor cell mobilization capability. Breast Cancer Res Treat 82:185–190PubMedCrossRefGoogle Scholar
  7. 7.
    Bargetzi MJ, Passweg J, Baertschi E, Schoenenberger A, Gwerder C, Tichelli A, Burger J, Mingrone W, Herrmann R, Gratwohl A, Wernli M (2003) Mobilization of peripheral blood progenitor cells with vinorelbine and granulocyte colony-stimulating factor in multiple myeloma patients is reliable and cost effective. Bone Marrow Transplant 31:99–103PubMedCrossRefGoogle Scholar
  8. 8.
    Barlogie B, Smith L, Alexanian R (1984) Effective treatment of advanced multiple myeloma refractory to alkylating agents. New Engl J Med 310:1353–1356PubMedGoogle Scholar
  9. 9.
    Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, Tricot G, Munshi N, Fassas A, Singhal S, Mehta J, Anaissie E, Dhodapkar D, Naucke S, Cromer J, Sawyer J, Epstein J, Spoon D, Ayers D, Cheson B, Crowley J (1999) Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 93:55–65PubMedGoogle Scholar
  10. 10.
    Barosi G, Boccadoro M, Cavo M, Corradini P, Marchetti M, Massaia M, Merlini G, Tosi P, Tura S for the Italian Society of Hematology, Italian Society of Experimental Hematology, Italian Group for Bone Marrow Transplantation (2004) Management of multiple myeloma and related-disorders: guidelines from the Italian Society of Hematology (SIE), Italian Society of Experimental Hematology (SIES) and Italian Group for Bone Marrow Transplantation (GITMO). Haematologica 89:717–741PubMedGoogle Scholar
  11. 11.
    Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D (1998) Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplantation. Br J Haemat 102:1115–1123CrossRefGoogle Scholar
  12. 12.
    Boiron JM, Marit G, Faberes C, Cony-Makhoul P, Foures C, Ferrer AM, Cristol G, Sarrat A, Girault D, Reiffers J (1993) Collection of peripheral blood stem cells in multiple myeloma with and without recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF). Bone Marrow Transplant 12:49–55PubMedGoogle Scholar
  13. 13.
    Caldera H, Giralt S (2004) Stem cell transplantation for multiple myeloma: current status and future directions. Curr Hematol Rep 3:249–256PubMedGoogle Scholar
  14. 14.
    Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ, Medical Research Council Adult Leukaemia Working Party (2003) High-dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma. New Engl J Med 348:1875–1883PubMedCrossRefGoogle Scholar
  15. 15.
    Desikan KR, Barlogie B, Jagannath S, Vesole DH, Siegel D, Fassas A, Munshi N, Singhal S, Mehta J, Tindle S, Nelson J, Bracy D, Mattox S, Tricot G (1998) Comparable engraftment kinetics following peripheral-blood stem-cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma. J Clin Oncol 16:1547–1553PubMedGoogle Scholar
  16. 16.
    Durie B, Salmon S (1975) A clinical staging system for multiple myeloma. Cancer 36:842–852PubMedCrossRefGoogle Scholar
  17. 17.
    Ferrara F, Palmieri S, Viola A, Copia C, Schiavone EM, De Simone M, Pocali B, D’Amico MR, Annunziata M, Mele G (2004) Outpatient-based peripheral blood stem cell transplantation for patients with multiple myeloma. Hematol J 5:222–226PubMedCrossRefGoogle Scholar
  18. 18.
    Fietz T, Rieger K, Dimeo F, Blau IW, Thiel E, Knauf WU (2004) Stem cell mobilization in multiple myeloma patients: do we need an age-adjusted regimen for the elderly? J Clin Apheresis 19:202–207PubMedCrossRefGoogle Scholar
  19. 19.
    Goldschmidt H, Hegenbart U, Haas R, Hunstein W (1996) Mobilization of peripheral blood progenitor cells with high-dose cyclophosphamide (4 or 7 g/m2) and granulocyte colony-stimulating factor in patients with multiple myeloma. Bone Marrow Transplant 17:691–697PubMedGoogle Scholar
  20. 20.
    Gratwohl A, EBMT JACIE Accreditation Office (2004). Overview of transplant activity in Europe. Hematology J 5(Suppl 3):S29–S33CrossRefGoogle Scholar
  21. 21.
    Harousseau JL, Maloisel F, Sotto JJ, Facon Th, Child T, Kelsey SM, Johnson S, Descheeemaker B, Moore L (1997) Vinorelbine (VRL) in patients with recurrent multiple myelomas (MM): a phase II study. Proc Am Soc Clin Oncol 16:37 (abstr)Google Scholar
  22. 22.
    Harousseau JL, Dammacco F, San Miguel J (1999) An alternative treatment for relapsed/resistant multiple myeloma (MM): Vinorelbine (VRL), plus high-dose dexamethasone (DEX): two phase II studies. Proc Am Soc Clin Oncol 18:107 (abstr)Google Scholar
  23. 23.
    Harousseau JL, Shaughnessy J Jr, Richardson P (2004) Multiple myeloma. Hematology (ASH Educational Program):237–256Google Scholar
  24. 24.
    Imrie K, Esmail R, Meyer RM, and the Members of the Hematology Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative (2002) The role of high-dose chemotherapy and stem-cell transplantation in patients with multiple myeloma: a practice guideline of the Cancer Care Ontario Practice Guidelines Initiative. Ann Int Med 136:619–629PubMedGoogle Scholar
  25. 25.
    Jantunen E, Putkonen M, Nousiainen T, Pelliniemi T, Mahlamaki T, Remes K (2003) Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony stimulating factor for progenitor cell mobilisation in patients with multiple myeloma. Bone Marrow Transplant 31:347–351PubMedCrossRefGoogle Scholar
  26. 26.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  27. 27.
    Kotasek D, Shepherd KM, Sage RE, Dale BM, Norman JE, Charles P, Gregg A, Pillow A, Bolton A (1992) Factors affecting blood stem cell collections following high-dose cyclophosphamide mobilization in lymphoma, myeloma and solid tumors. Bone Marrow Transplant 9:11–17PubMedGoogle Scholar
  28. 28.
    Kyle RA, Rajkumar SV (2004) Multiple myeloma. New Engl J Med 351:1860–1873PubMedCrossRefGoogle Scholar
  29. 29.
    Lahuerta JJ (2000) Remission status defined by immunofixation vs electrophoresis after autologous transplant has a major impact on the outcome of multiple myeloma patients. Br J Haemat 109:438–446CrossRefGoogle Scholar
  30. 30.
    Lerro KA, Medoff E, Wu Y, Seropian SE, Snyder E, Krause D, Cooper DL (2003) A simplified approach to stem cell mobilization in multiple myeloma patients not previously treated with alkylating agents. Bone Marrow Transplant 32:1113–1117PubMedCrossRefGoogle Scholar
  31. 31.
    Magagnoli M, Sarina B, Balzarotti M, Castagna L, Timofeeva I, Nozza A, Bertuzzi A, Siracusano L, Sinnone M, Santoro A (2001) Mobilizing potential of ifosfamide/vinorelbine-based chemotherapy in pretreated malignant lymphoma. Bone Marrow Transplant 28:923–927PubMedCrossRefGoogle Scholar
  32. 32.
    Morris TC, Velangi M, Jackson G, Marks DI, Ranaghan L (2005) Less than half of patients aged 65 years or under with myeloma proceed to transplantation: results of a two region population-based survey. Br J Haemat 128:510–512CrossRefGoogle Scholar
  33. 33.
    Olivieri A, Capelli D, Montanari M, Brunori M, Massidda D, Poloni A, Lucesole M, Centurioni R, Candela M, Masia MC, Tonnini C, Leoni P (2001) Very low toxicity and good quality of life in 48 elderly patients autotransplanted for hematological malignancies: a single center experience. Bone Marrow Transplant 27:1189–1195PubMedCrossRefGoogle Scholar
  34. 34.
    Petrucci MT, Avvisati G, La Verde G, De Fabritiis P, Ribersani M, Palumbo G, De Felice L, Rusignuolo A, Simone F, Meloni G, Mandelli F (2003) Intermediate-dose cyclophosphamide and granulocyte colony-stimulating factor is a valid alternative to high-dose cyclophosphamide for mobilizing peripheral blood CD34+ cells in patients with multiple myeloma. Acta Haematol 109:84–188CrossRefGoogle Scholar
  35. 35.
    Reece DE, Bredeson C, Perez WS, Jagannath S, Zhang MJ, Ballen KK, Elfenbein GJ, Freytes CO, Gale RP, Gertz MA, Gibson J, Giralt SA, Keating A, Kyle RA, Maharaj D, Marcellus D, McCarthy PL, Milone GA, Nimer SD, Pavlovsky S, To LB, Weisdorf DJ, Wiernik PH, Wingard JR, Vesole DH (2003) Autologous stem cell transplantation in multiple myeloma patients<60 vs >/=60 years of age. Bone Marrow Transplant 32:1135–1143PubMedCrossRefGoogle Scholar
  36. 36.
    Siegel DS, Desikan KR, Mehta J, Singhal S, Fassas A, Munshi N, Anaissie E, Naucke S, Ayers D, Spoon D, Vesole D, Tricot G, Barlogie B (1999) Age is not a prognostic variable with autotransplants for multiple myeloma. Blood 93:51–54PubMedGoogle Scholar
  37. 37.
    Sirohi B, Powles R (2004) Multiple myeloma. Lancet 363:875–887PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Mario Annunziata
    • 1
  • Maria Celentano
    • 1
  • Barbara Pocali
    • 1
  • Maria Rosaria D’Amico
    • 1
  • Salvatore Palmieri
    • 1
  • Assunta Viola
    • 1
  • Carolina Copia
    • 1
  • Claudio Falco
    • 1
    • 2
  • Luigi Del Vecchio
    • 1
    • 2
  • Felicetto Ferrara
    • 1
    • 3
  1. 1.Division of Hematology and Stem Cell Transplantation UnitCardarelli HospitalNaplesItaly
  2. 2.Service of Transfusion MedicineCardarelli HospitalNaplesItaly
  3. 3.Via Nicolò Piccinni 6NapoliItaly

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