Abstract
We report 13 multiple myeloma (MM) or lymphoma patients who were failing PBSC mobilization after disease-specific chemotherapy and granulocyte-CSF (G-CSF), and received plerixafor to successfully collect PBSCs. Patients were considered poor mobilizers when the concentration of PB CD34+ cells was always lower than 10 cells/μL, during the recovery phase after chemotherapy and/or were predicted to have inadequate PBSC collection to proceed to autologous transplantation. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to three consecutive days, while continuing G-CSF, 10–11 h before the planned leukapheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a 4.7 median fold-increase in the number of circulating CD34+ cells after plerixafor as compared with baseline CD34+ cell concentration (from a median of 6.2 (range 1–12) to 21.5 (range 9–88) cells/μL). All patients collected >2 × 106 CD34+ cells/kg in 1–3 leukaphereses. In all, 5/13 patients have already undergone autograft with plerixafor-mobilized PBSCs, showing a rapid and durable hematological recovery. Our results suggest that the pre-emptive addition of plerixafor to G-CSF after chemotherapy is safe and may allow the rescue of lymphoma and MM patients, who need autologous transplantation but are failing PBSC mobilization.
Similar content being viewed by others
References
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. Erratum in: N Engl J Med 2004; 350(25):2628.
Sureda A, Arranz R, Iriondo A, Carreras E, Lahuerta JJ, García-Conde J et al. Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Espanol de Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol 2001; 19: 1395–1404.
Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P et al. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood 1991; 77: 1587–1592.
Allan DS, Keeney M, Howson-Jan K, Popma J, Weir K, Bhatia M et al. Number of viable CD34+ cells reinfused predicts engraftment in autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 2002; 29: 967–972.
Bensinger W, DiPersio JF, McCarty JM . Improving stem cell mobilization strategies: future directions. Bone Marrow Transplant 2009; 43: 181–195.
Lemoli RM, D’Addio A . Hematopoietic stem cell mobilization. Haematologica 2008; 93: 321–324.
Hübel K, Liles WC, Broxmeyer HE, Rodger E, Wood B, Cooper S et al. Leukocytosis and mobilization of CD34+ hematopoietic progenitor cells by AMD3100, a CXCR4 antagonist. Support Cancer Ther 2004; 1: 165–172.
Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin′s lymphoma. J Clin Oncol 2004; 22: 1095–1102.
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 2008; 41: 331–338.
Dipersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol 2009; 27: 4767–4773.
DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009; 113: 5720–5726.
Jantunen E, Putkonen M, Nousiainen T, Pelliniemi TT, Mahlamäki E, Remes K et al. Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor for progenitor cell mobilisation in patients with multiple myeloma. Bone Marrow Transplant 2003; 31: 347–351.
Isidori A, Tani M, Bonifazi F, Zinzani P, Curti A, Motta MR et al. Phase II study of a single pegfilgrastim injection as an adjunct to chemotherapy to mobilize stem cells into the peripheral blood of pretreated lymphoma patients. Haematologica 2005; 90: 225–231.
Dugan MJ, Maziarz RT, Bensinger WI, Nademanee A, Liesveld J, Badel K et al. Safety and preliminary efficacy of plerixafor (Mozobil) in combination with chemotherapy and G-CSF: an open-label, multicenter, exploratory trial in patients with multiple myeloma and non-Hodgkin's lymphoma undergoing stem cell mobilization. Bone Marrow Transplant 2010; 45: 39–47.
Hussein MA, Bolejack V, Zonder JA, Durie BG, Jakubowiak AJ, Crowley JJ et al. Phase II study of thalidomide plus dexamethasone induction followed by tandem melphalan-based autotransplantation and thalidomide-plus-prednisone maintenance for untreated multiple myeloma: a southwest oncology group trial (S0204). J Clin Oncol 2009; 27: 3510–3517.
Palumbo A, Rajkumar SV . Treatment of newly diagnosed myeloma. Leukemia 2009; 23: 449–456.
Zinzani PL, Martelli M, Magagnoli M, Zaja F, Storti S, Pavone E et al. How do patients with aggressive non-Hodgkin's lymphoma treated with third-generation regimens (MACOP-B and F-MACHOP) fare in the long-term? Haematologica 1999; 84: 996–1001.
Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 235–242.
Zinzani PL, Tani M, Fanti S, Stefoni V, Musuraca G, Vitolo U et al. A phase 2 trial of fludarabine and mitoxantrone chemotherapy followed by yttrium-90 ibritumomab tiuxetan for patients with previously untreated, indolent, nonfollicular, non-Hodgkin lymphoma. Cancer 2008; 112: 856–862.
Brusamolino E, Bacigalupo A, Barosi G, Biti G, Gobbi PG, Levis A et al. Hodgkin's lymphoma in adults: guidelines of the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation on initial work-up, management, and follow-up. Haematologica 2009; 94: 550–565.
Bishton MJ, Lush RJ, Byrne JL, Russell NH, Shaw BE, Haynes AP . Ifosphamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant-eligible patients with non-Hodgkin lymphoma and Hodgkin disease. Br J Haematol 2007; 136: 752–761.
Hagberg H, Gisselbrecht C . CORAL study group. Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol 2006; 17 (Suppl 4): iv31–iv32.
Weide R, Hess G, Köppler H, Heymanns J, Thomalla J, Aldaoud A et al. High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk Lymphoma 2007; 48: 1299–1306.
Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS et al. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol 2005; 23: 9208–9218.
Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2004; 104: 3064–3071.
Witzig TE, Geyer SM, Kurtin PJ, Colgan JP, Inwards DJ, Micallef IN et al. Salvage chemotherapy with rituximab DHAP for relapsed non-Hodgkin lymphoma: a phase II trial in the North Central Cancer Treatment Group. Leuk Lymphoma 2008; 49: 1074–1080.
Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM et al. R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica 2008; 93: 1829–1836.
Perea G, Sureda A, Martino R, Altés A, Martinez C, Cabezudo E et al. Predictive factors for a successful mobilization of peripheral blood CD34+ cells in multiple myeloma. Ann Hematol 2001; 80: 592–597.
Morris CL, Siegel E, Barlogie B, Cottler-Fox M, Lin P, Fassas A et al. Mobilization of CD34+ cells in elderly patients (⩾70 years) with multiple myeloma: influence of age, prior therapy, platelet count and mobilization regimen. Br J Haematol 2003; 120: 413–423.
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.
Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W, Comenzo RL et al. International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia 2009; 23: 1904–1912.
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.
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 2007; 22: 1280–1281.
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.
Kuittinen T, Nousiainen T, Halonen P, Mahlamäki E, Jantunen E . Prediction of mobilisation failure in patients with non-Hodgkin's lymphoma. Bone Marrow Transplant 2004; 33: 907–912.
Tarella C, Di Nicola M, Caracciolo D, Zallio F, Cuttica A, Omedè P et al. High-dose ara-C with autologous peripheral blood progenitor cell support induces a marked progenitor cell mobilization: an indication for patients at risk for low mobilization. Bone Marrow Transplant 2002; 30: 725–732.
Douglas K, Hayden P, Rahemtulla A, D’Addio A, Rao K, Maris M et al. Plerixafor for PBSC mobilization in myeloma patients with advanced renal failure: safety and efficacy data in a series of 12 patients from the US or European Compassionate Use Programmes and from the US post-licensing. Bone Marrow Transplant 2010; 45 (Suppl.2): S3–S23.
Acknowledgements
This work was in part supported by Italian Ministry of Health (Progetto Strategico Oncologia, 2006), Regione Emilia-Romagna (Progetti di Ricerca Università-Regione Emilia Romagna, Progetto Medicina Rigenerativa, 2007), Italian Association Against Leukemia, Bologna (BolognAil).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
Professor Roberto M Lemoli has received research support and compensation as a member of the scientific advisory board of Genzyme, Italy.
Rights and permissions
About this article
Cite this article
D'Addio, A., Curti, A., Worel, N. et al. The addition of plerixafor is safe and allows adequate PBSC collection in multiple myeloma and lymphoma patients poor mobilizers after chemotherapy and G-CSF. Bone Marrow Transplant 46, 356–363 (2011). https://doi.org/10.1038/bmt.2010.128
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2010.128
- Springer Nature Limited
Keywords
This article is cited by
-
Stem cell mobilization in multiple myeloma: challenges, strategies, and current developments
Annals of Hematology (2023)
-
The timing of plerixafor addition to G-Csf and chemotherapy affects immunological recovery after autologous stem cell transplant in multiple myeloma
Bone Marrow Transplantation (2020)
-
Preemptive plerixafor injection added to pegfilgrastim after chemotherapy in non-Hodgkin lymphoma patients mobilizing poorly
Annals of Hematology (2017)
-
Upfront plerixafor plus G-CSF versus cyclophosphamide plus G-CSF for stem cell mobilization in multiple myeloma: efficacy and cost analysis study
Bone Marrow Transplantation (2016)
-
Prognostic factors for re-mobilization using plerixafor and granulocyte colony-stimulating factor (G-CSF) in patients with malignant lymphoma or multiple myeloma previously failing mobilization with G-CSF with or without chemotherapy: the Korean multicenter retrospective study
Annals of Hematology (2016)