Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Novel agents and approaches for stem cell mobilization in normal donors and patients

Bone Marrow Transplantation volume 47, pages 1154–1163 (2012)Cite this article

Subjects

Abstract

In spite of the safety and efficiency of the classical mobilization protocols, recombinant human G-CSF±chemotherapy, there is still a considerable amount of mobilization failures (10–30%), which warrant novel agents and approaches both in an autologous and an allogeneic transplant setting. Attempts to improve CD34+ yields by using several cytokines and growth factors as adjuncts to G-CSF could not change the standard approaches during the last decade, either because of inefficiency or the adverse events encountered with these agents. As a long-acting G-CSF analog, pegfilgrastim has the advantages of an earlier start of apheresis, reduction in the number of apheresis procedures as well as a reduced number of injections as compared with unconjugated G-CSF. However, dosing and cost-effectiveness especially in cytokine-only mobilizations require further investigation. As interactions between hematopoietic stem cells and the BM microenvironment are better understood, new molecules targeting these interactions are emerging. Plerixafor, which started its journey as an anti-HIV drug, recently ended up being a popular stem cell mobilizer with the ability of rapid mobilization and gained approval as an adjunct to G-CSF for poor mobilizers. At present, it is challenging to search for the best approach by using the available drugs with appropriate timing to provide sufficient CD34+ yield after an initial mobilization attempt, and in a cost-effective manner thereby avoiding further mobilization attempts and exposure to chemotherapy. Approaches not only for increasing stem cell yield, but also aiming to improve the quality of graft content and the associated transplantation outcomes are promising areas of research.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Cashen AF, Lazarus HM, Devine SM . Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF? Bone Marrow Transplant 2007; 39: 577–588.

    Article  CAS  PubMed  Google Scholar 

  2. Demirer T, Bensinger WI, Buckner CD . Peripheral blood stem cell mobilization for high dose chemotherapy. J Hematother 1999; 8: 103–113.

    Article  CAS  PubMed  Google Scholar 

  3. Demirer T, Aylı M, Ozcan M, Gunel N, Haznedar R, Dagli M et al. Mobilization of peripheral blood stem cells with chemotherapy and recombinant human granulocyte-colony stimulating factor (Rh-GSCF): a randomized evaluation of different doses of Rh-GSCF. Br J Haematol 2002; 116: 468–472.

    Article  CAS  PubMed  Google Scholar 

  4. Martínez C, Urbano-Ispizua A, Marín P, Merino A, Rovira M, Carreras E et al. Efficacy and toxicity of a high-dose G-CSF schedule for peripheral blood progenitor cell mobilization in healthy donors. Bone Marrow Transplant 1999; 24: 1273–1278.

    Article  PubMed  Google Scholar 

  5. Kim MK, Kim S, Lee SS, Sym SJ, Lee DH, Kim SW et al. Rituximab–ESHAP as a mobilization regimen for relapsed or refractory B-cell lymphomas: a comparison with ESHAP. Transfusion 2007; 47: 1447–1454.

    Article  CAS  PubMed  Google Scholar 

  6. Hosing C, Saliba RM, Körbling M, Acholonu S, McMannis J, Anderlini P et al. High-dose rituximab does not negatively affect peripheral blood stem cell mobilization kinetics in patients with intermediate-grade non-Hodgkin's lymphoma. Leuk Lymphoma 2006; 47: 1290–1294.

    Article  CAS  PubMed  Google Scholar 

  7. Copelan E, Pohlman B, Rybicki L, Kalaycio M, Sobecks R, Andresen S et al. A randomized trial of etoposide and G-CSF with or without rituximab for PBSC mobilization in B-cell non-Hodgkin's lymphoma. Bone Marrow Transplant 2009; 43: 101–105.

    Article  CAS  PubMed  Google Scholar 

  8. Benekli M, Hahn T, Shafi F, Qureshi A, Alam AR, Czuczman MS et al. Effect of rituximab on peripheral blood stem cell mobilization and engraftment kinetics in non-Hodgkin's lymphoma patients. Bone Marrow Transplant 2003; 32: 139–143.

    Article  CAS  PubMed  Google Scholar 

  9. Dingli D, Nowakowski GS, Dispenzieri A, Lacy MQ, Hayman S, Litzow MR et al. Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma. Clin Lymphoma Myeloma 2006; 6: 384–388.

    Article  CAS  PubMed  Google Scholar 

  10. 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  PubMed  Google Scholar 

  11. 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 

  12. Mark T, Stern J, Furst JR, Jayabalan D, Zafar F, LaRow A et al. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant 2008; 14: 795–798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ozcelik T, Topcuoglu P, Beksac M, Ozcan M, Arat M, Biyikli Z et al. Mobilization of PBPCs with chemotherapy and recombinant human G-CSF: a randomized evaluation of early vs late administration of recombinant human G-CSF. Bone Marrow Transplant 2009; 44: 779–783.

    Article  CAS  PubMed  Google Scholar 

  14. Kopf B, De Giorgi U, Vertogen B, Monti G, Molinari A, Turci D et al. A randomized study comparing filgrastim versus lenograstim versus molgramostim plus chemotherapy for peripheral blood progenitor cell mobilization. Bone Marrow Transplant 2006; 38: 407–412.

    Article  CAS  PubMed  Google Scholar 

  15. Martino M, Console G, Dattola A, Callea I, Messina G, Moscato T et al. Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience. Bone Marrow Transplant 2009; 44: 163–168.

    Article  CAS  PubMed  Google Scholar 

  16. Leung AY, Kwong YL . Haematopoietic stem cell transplantation: current concepts and novel therapeutic strategies. Br Med Bull 2010; 93: 85–103.

    Article  CAS  PubMed  Google Scholar 

  17. Bensinger W, DiPersio JF, McCarty JM . Improving stem cell mobilization strategies: future directions. Bone Marrow Transplant 2009; 43: 181–195.

    Article  CAS  PubMed  Google Scholar 

  18. Gertz MA . Current status of stem cell mobilization. Br J Haematol 2010; 150: 647–662.

    Article  CAS  PubMed  Google Scholar 

  19. Sheridan WP, Begley CG, To LB, Grigg A, Szer J, Maher D et al. Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood progenitor cells to restore hemopoiesis after high-dose chemotherapy for lymphoid malignancies. Bone Marrow Transplant 1994; 14: 105–111.

    CAS  PubMed  Google Scholar 

  20. Kröger N, Zander AR . Dose and schedule effect of G-GSF for stem cell mobilization in healthy donors for allogeneic transplantation. Leuk Lymphoma 2002; 43: 1391–1394.

    Article  PubMed  CAS  Google Scholar 

  21. Engelhardt M, Bertz H, Afting M, Waller CF, Finke J . High-versus standard-dose filgrastim (rhG-CSF) for mobilization of peripheral-blood progenitor cells from allogeneic donors and CD34(+) immunoselection. J Clin Oncol 1999; 17: 2160–2172.

    Article  CAS  PubMed  Google Scholar 

  22. Lane TA, Law P, Maruyama M, Young D, Burgess J, Mullen M et al. Harvesting and enrichment of hematopoietic progenitor cells mobilized into the peripheral blood of normal donors by granulocyte–macrophage colony-stimulating factor (GM-CSF) or G-CSF: potential role in allogeneic marrow transplantation. Blood 1995; 85: 275–282.

    CAS  PubMed  Google Scholar 

  23. Spitzer G, Adkins D, Mathews M, Velasquez W, Bowers C, Dunphy F et al. Randomized comparison of G-CSF+GM-CSF vs G-CSF alone for mobilization of peripheral blood stem cells: effects on hematopoietic recovery after high-dose chemotherapy. Bone Marrow Transplant 1997; 20: 921–930.

    Article  CAS  PubMed  Google Scholar 

  24. Gazitt Y . Comparison between granulocyte colony-stimulating factor and granulocyte–macrophage colony-stimulating factor in the mobilization of peripheral blood stem cells. Curr Opin Hematol 2002; 9: 190–198.

    Article  PubMed  Google Scholar 

  25. Boeve S, Strupeck J, Creech S, Stiff PJ . Analysis of remobilization success in patients undergoing autologous stem cell transplants who fail an initial mobilization: risk factors, cytokine use and cost. Bone Marrow Transplant 2004; 33: 997–1003.

    Article  CAS  PubMed  Google Scholar 

  26. Koç 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  PubMed  Google Scholar 

  27. Devine SM, Brown RA, Mathews V, Trinkaus K, Khoury H, Adkins D et al. Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone. Bone Marrow Transplant 2005; 36: 531–538.

    Article  CAS  PubMed  Google Scholar 

  28. Vasu C, Dogan RN, Holterman MJ, Prabhakar BS . Selective induction of dendritic cells using granulocyte macrophage-colony stimulating factor, but not fms-like tyrosine kinase receptor 3-ligand, activates thyroglobulin-specific CD4+/CD25+ T cells and suppresses experimental autoimmune thyroiditis. J Immunol 2003; 170: 5511–5522.

    Article  CAS  PubMed  Google Scholar 

  29. Parajuli P, Mosley RL, Pisarev V, Chavez J, Ulrich A, Varney M et al. Flt3 ligand and granulocyte–macrophage colony-stimulating factor preferentially expand and stimulate different dendritic and T-cell subsets. Exp Hematol 2001; 29: 1185–1193.

    Article  CAS  PubMed  Google Scholar 

  30. 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 

  31. 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 

  32. 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 

  33. 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 

  34. Hart C, Grassinger J, Andreesen R, Hennemann B . 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 2009; 43: 197–206.

    Article  CAS  PubMed  Google Scholar 

  35. Labonté L, Iqbal T, McDiarmid S, Bence-Bruckler I, Huebsch L, Allan D . Continuing erythropoietin during peripheral blood stem cell collection in myeloma: can it reduce toxicity of autologous transplants? Biol Blood Marrow Transplant 2008; 14: 132–133.

    Article  PubMed  Google Scholar 

  36. Glaspy JA, Shpall EJ, LeMaistre CF, Briddell RA, Menchaca DM, Turner SA et al. Peripheral blood progenitor cell mobilization using stem cell factor in combination with filgrastim in breast cancer patients. Blood 1997; 90: 2939–2951.

    CAS  PubMed  Google Scholar 

  37. Weaver A, Chang J, Wrigley E, de Wynter E, Woll PJ, Lind M et al. Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer. J Clin Oncol 1998; 16: 2601–2612.

    Article  CAS  PubMed  Google Scholar 

  38. Facon T, Harousseau JL, Maloisel F, Attal M, Odriozola J, Alegre A et al. Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial. Blood 1999; 94: 1218–1225.

    CAS  PubMed  Google Scholar 

  39. Shpall EJ, Wheeler CA, Turner SA, Yanovich S, Brown RA, Pecora AL et al. A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high-risk breast cancer patients. Blood 1999; 93: 2491–2501.

    CAS  PubMed  Google Scholar 

  40. Stiff P, Gingrich R, Luger S, Wyres MR, Brown RA, LeMaistre CF et al. A randomized phase 2 study of PBPC mobilization by stem cell factor and filgrastim in heavily pretreated patients with Hodgkin's disease or non-Hodgkin's lymphoma. Bone Marrow Transplant 2000; 26: 471–481.

    Article  CAS  PubMed  Google Scholar 

  41. Dawson MA, Schwarer AP, Muirhead JL, Bailey MJ, Bollard GM, Spencer A . Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen. Bone Marrow Transplant 2005; 36: 389–396.

    Article  CAS  PubMed  Google Scholar 

  42. Mijovic A, Russell N, Clark RE, Morris TC, Browne P, Crown J et al. Ancestim associated with filgrastim and/or chemotherapy can improve blood progenitor yields in patients who previously failed mobilisation. Bone Marrow Transplant 2005; 35: 1019.

    Article  CAS  PubMed  Google Scholar 

  43. Herbert KE, Morgan S, Prince HM, Westerman DA, Wolf MM, Carney DA et al. Stem cell factor and high-dose twice daily filgrastim is an effective strategy for peripheral blood stem cell mobilization in patients with indolent lymphoproliferative disorders previously treated with fludarabine: results of a phase II study with an historical comparator. Leukemia 2009; 23: 305–312.

    Article  CAS  PubMed  Google Scholar 

  44. Costa JJ, Demetri GD, Harrist TJ, Dvorak AM, Hayes DF, Merica EA et al. Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J Exp Med 1996; 183: 2681–2686.

    Article  CAS  PubMed  Google Scholar 

  45. Murray LJ, Luens KM, Estrada MF, Bruno E, Hoffman R, Cohen RL et al. Thrombopoietin mobilizes CD34+ cell subsets into peripheral blood and expands multilineage progenitors in bone marrow of cancer patients with normal hematopoiesis. Exp Hematol 1998; 26: 207–216.

    CAS  PubMed  Google Scholar 

  46. Somlo G, Sniecinski I, ter Veer A, Longmate J, Knutson G, Vuk-Pavlovic S et al. Recombinant human thrombopoietin in combination with granulocyte colony-stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy. Blood 1999; 93: 2798–2806.

    CAS  PubMed  Google Scholar 

  47. Linker C, Anderlini P, Herzig R, Christiansen N, Somlo G, Bensinger W et al. Recombinant human thrombopoietin augments mobilization of peripheral blood progenitor cells for autologous transplantation. Biol Blood Marrow Transplant 2003; 9: 405–413.

    Article  CAS  PubMed  Google Scholar 

  48. Gajewski JL, Rondon G, Donato ML, Anderlini P, Korbling M, Ippoliti C et al. Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor for peripheral blood progenitor cell mobilization. Biol Blood Marrow Transplant 2002; 8: 550–556.

    Article  CAS  PubMed  Google Scholar 

  49. Nplate (Romiplostim) [package insert] Amgen Inc.: Thousand Oaks, CA, 2008.

  50. Promacta (Eltrombopag) [package insert] GSK Inc.: Research Triangle Park, NC, 2008.

  51. Neulasta (Pegfilgrastim) [package insert]. Amgen Inc.: Thousand Oaks, CA, 2007.

  52. Hunter MG, Druhan LJ, Massullo PR, Avalos BR . Proteolytic cleavage of granulocyte colony-stimulating factor and its receptor by neutrophil elastase induces growth inhibition and decreased cell surface expression of the granulocyte colony-stimulating factor receptor. Am J Hematol 2003; 74: 149–155.

    Article  CAS  PubMed  Google Scholar 

  53. Molineux G, Kinstler O, Briddell B, Hartley C, McElroy P, Kerzic P et al. A new form of filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. Exp Hematol 1999; 27: 1724–1734.

    Article  CAS  PubMed  Google Scholar 

  54. Steidl U, Fenk R, Bruns I, Neumann F, Kondakci M, Hoyer B et al. Successful transplantation of peripheral blood stem cells mobilized by chemotherapy and a single dose of pegylated G-CSF in patients with multiple myeloma. Bone Marrow Transplant 2005; 35: 33–36.

    Article  CAS  PubMed  Google Scholar 

  55. Fruehauf S, Klaus J, Huesing J, Veldwijk MR, Buss EC, Topaly J et al. Efficient mobilization of peripheral blood stem cells following CAD chemotherapy and a single dose of pegylated G-CSF in patients with multiple myeloma. Bone Marrow Transplant 2007; 39: 743–750.

    Article  CAS  PubMed  Google Scholar 

  56. 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.

    CAS  PubMed  Google Scholar 

  57. Kroschinsky F, Hölig K, Platzbecker U, Poppe-Thiede K, Ordemann R, Blechschmidt M et al. Efficacy of single-dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma. Transfusion 2006; 46: 1417–1423.

    Article  CAS  PubMed  Google Scholar 

  58. Putkonen M, Rauhala A, Pelliniemi TT, Remes K . Single-dose pegfilgrastim is comparable to daily filgrastim in mobilizing peripheral blood stem cells: a case-matched study in patients with lymphoproliferative malignancies. Ann Hematol 2009; 88: 673–680.

    Article  PubMed  Google Scholar 

  59. Simona B, Cristina R, Luca N, Sara S, Aleksandra B, Paola B et al. A single dose of pegfilgrastim versus daily filgrastim to evaluate the mobilization and the engraftment of autologous peripheral hematopoietic progenitors in malignant lymphoma patients candidate for high-dose chemotherapy. Transfus Apher Sci 2010; 43: 321–326.

    Article  Google Scholar 

  60. Bruns I, Steidl U, Kronenwett R, Fenk R, Graef T, Rohr UP et al. A single dose of 6 or 12 mg of pegfilgrastim for peripheral blood progenitor cell mobilization results in similar yields of CD34+ progenitors in patients with multiple myeloma. Transfusion 2006; 46: 180–185.

    Article  CAS  PubMed  Google Scholar 

  61. Russell N, Mesters R, Schubert J, Boogaerts M, Johnsen HE, Canizo CD et al. A phase 2 pilot study of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin's lymphoma receiving chemotherapy. Haematologica 2008; 93: 405–412.

    Article  CAS  PubMed  Google Scholar 

  62. Tricot G, Barlogie B, Zangari M, van Rhee F, Hoering A, Szymonifka J et al. Mobilization of peripheral blood stem cells in myeloma with either pegfilgrastim or filgrastim following chemotherapy. Haematologica 2008; 93: 1739–1742.

    Article  CAS  PubMed  Google Scholar 

  63. Willis F, Woll P, Theti D, Jamali H, Bacon P, Baker N et al. Pegfilgrastim for peripheral CD34+ mobilization in patients with solid tumours. Bone Marrow Transplant 2009; 43: 927–934.

    Article  CAS  PubMed  Google Scholar 

  64. Hosing C, Qazilbash MH, Kebriaei P, Giralt S, Davis MS, Popat U et al. Fixed-dose single agent pegfilgrastim for peripheral blood progenitor cell mobilisation in patients with multiple myeloma. Br J Haematol 2006; 133: 533–537.

    Article  CAS  PubMed  Google Scholar 

  65. Kroschinsky F, Hölig K, Poppe-Thiede K, Zimmer K, Ordemann R, Blechschmidt M et al. Single-dose pegfilgrastim for the mobilization of allogeneic CD34+ peripheral blood progenitor cells in healthy family and unrelated donors. Haematologica 2005; 90: 1665–1671.

    CAS  PubMed  Google Scholar 

  66. Hill GR, Morris ES, Fuery M, Hutchins C, Butler J, Grigg A et al. Allogeneic stem cell transplantation with peripheral blood stem cells mobilized by pegylated G-CSF. Biol Blood Marrow Transplant 2006; 12: 603–607.

    Article  PubMed  Google Scholar 

  67. Morris ES, MacDonald KP, Hill GR . Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL? Blood 2006; 107: 3430–3435.

    Article  CAS  PubMed  Google Scholar 

  68. Fenk R, Hieronimus N, Steidl U, Bruns I, Graef T, Zohren F et al. Sustained G-CSF plasma levels following administration of pegfilgrastim fasten neutrophil reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation in patients with multiple myeloma. Exp Hematol 2006; 34: 1296–1302.

    Article  CAS  PubMed  Google Scholar 

  69. Rosenbeck LL, Srivastava S, Kiel PJ . Peripheral blood stem cell mobilization tactics. Ann Pharmacother 2010; 44: 107–116.

    Article  CAS  PubMed  Google Scholar 

  70. Nervi B, Link DC, DiPersio JF . Cytokines and hematopoietic stem cell mobilization. J Cell Biochem 2006; 99: 690–705.

    Article  CAS  PubMed  Google Scholar 

  71. Pelus LM, Horowitz D, Cooper SC, King AG . Peripheral blood stem cell mobilization. A role for CXC chemokines. Crit Rev Oncol Hematol 2002; 43: 257–275.

    Article  PubMed  Google Scholar 

  72. Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA . A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 1996; 184: 1101–1109.

    Article  CAS  PubMed  Google Scholar 

  73. Baggiolini M . Chemokines and leukocyte traffic. Nature 1998; 392: 565–568.

    Article  CAS  PubMed  Google Scholar 

  74. King AG, Horowitz D, Dillon SB, Levin R, Farese AM, MacVittie TJ et al. Rapid mobilization of murine hematopoietic stem cells with enhanced engraftment properties and evaluation of hematopoietic progenitor cell mobilization in rhesus monkeys by a single injection of SB-251353, a specific truncated form of the human CXC chemokine GRObeta. Blood 2001; 97: 1534–1542.

    Article  CAS  PubMed  Google Scholar 

  75. Pelus LM, Fukuda S . Peripheral blood stem cell mobilization: the CXCR2 ligand GRObeta rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties. Exp Hematol 2006; 34: 1010–1020.

    Article  CAS  PubMed  Google Scholar 

  76. Fukuda S, Bian H, King AG, Pelus LM . The chemokine GRObeta mobilizes early hematopoietic stem cells characterized by enhanced homing and engraftment. Blood 2007; 110: 860–869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pelus LM, Fukuda S . Chemokine-mobilized adult stem cells; defining a better hematopoietic graft. Leukemia 2008; 22: 466–473.

    Article  CAS  PubMed  Google Scholar 

  78. Hatse S, Princen K, Bridger G, De Clercq E, Schols D . Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. FEBS Lett 2002; 527: 255–262.

    Article  CAS  PubMed  Google Scholar 

  79. Gerlach LO, Skerlj RT, Bridger GJ, Schwartz TW . Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J Biol Chem 2001; 276: 14153–14160.

    Article  CAS  PubMed  Google Scholar 

  80. Hendrix CW, Flexner C, MacFarland RT, Giandomenico C, Fuchs EJ, Redpath E et al. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob Agents Chemother 2000; 44: 1667–1673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lack NA, Green B, Dale DC, Calandra GB, Lee H, MacFarland RT et al. A pharmacokinetic–pharmacodynamic model for the mobilization of CD34+ hematopoietic progenitor cells by AMD3100. Clin Pharmacol Ther 2005; 77: 427–436.

    Article  CAS  PubMed  Google Scholar 

  82. Liles WC, Broxmeyer HE, Rodger E, Wood B, Hübel K, Cooper S et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 2003; 102: 2728–2730.

    Article  CAS  PubMed  Google Scholar 

  83. Liles WC, Rodger E, Broxmeyer HE, Dehner C, Badel K, Calandra G et al. Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist. Transfusion 2005; 45: 295–300.

    Article  CAS  PubMed  Google Scholar 

  84. Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD 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 

  85. Stewart DA, Smith C, MacFarland R, Calandra G . Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma. Biol Blood Marrow Transplant 2009; 15: 39–46.

    Article  CAS  PubMed  Google Scholar 

  86. Cashen A, Lopez S, Gao F, Calandra G, MacFarland R, Badel K et al. A phase II study of plerixafor (AMD3100) plus G-CSF for autologous hematopoietic progenitor cell mobilization in patients with Hodgkin lymphoma. Biol Blood Marrow Transplant 2008; 14: 1253–1261.

    Article  CAS  PubMed  Google Scholar 

  87. Stiff P, Micallef I, McCarthy P, Magalhaes-Silverman M, Weisdorf D, Territo M et al. Treatment with plerixafor in non-Hodgkin's lymphoma and multiple myeloma patients to increase the number of peripheral blood stem cells when given a mobilizing regimen of G-CSF: implications for the heavily pretreated patient. Biol Blood Marrow Transplant 2009; 15: 249–256.

    Article  CAS  PubMed  Google Scholar 

  88. 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 

  89. DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL et al. 3102 Investigators. 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.

    CAS  PubMed  Google Scholar 

  90. DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E et al. 3101 Investigators. 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.

    Article  CAS  PubMed  Google Scholar 

  91. Mozobil (Plerixafor) [product information]. Genzyme Co.: Cambridge, MA, 2008.

  92. 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.

    Article  CAS  PubMed  Google Scholar 

  93. 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.

    Article  CAS  PubMed  Google Scholar 

  94. Shaughnessy P, Islas-Ohlmayer M, Murphy J, Hougham M, Macpherson J, Winkler K et al. Cost and clinical analysis of autologous hematopoietic stem cell mobilization with G-CSF and plerixafor compared to G-CSF and cyclophosphamide. Biol Blood Marrow Transplant 2011; 17: 729–736.

    Article  CAS  PubMed  Google Scholar 

  95. Costa LJ, Miller AN, Alexander ET, Hogan KR, Shabbir M, Schaub C et al. Growth factor and patient-adapted use of plerixafor is superior to CY and growth factor for autologous hematopoietic stem cells mobilization. Bone Marrow Transplant 2011; 46: 523–528.

    Article  CAS  PubMed  Google Scholar 

  96. Costa LJ, Alexander ET, Hogan KR, Schaub C, Fouts TV, Stuart RK . Development and validation of a decision-making algorithm to guide the use of plerixafor for autologous hematopoietic stem cell mobilization. Bone Marrow Transplant 2011; 46: 64–69.

    Article  CAS  PubMed  Google Scholar 

  97. Duong HK, Bolwell BJ, Rybicki L, Koo A, Hsi ED, Figueroa P et al. Predicting hematopoietic stem cell mobilization failure in patients with multiple myeloma: a simple method using day 1 CD34+ cell yield. J Clin Apher 2011; 26: 111–115.

    Article  PubMed  Google Scholar 

  98. Fruehauf S, Ehninger G, Hübel K, Topaly J, Goldschmidt H, Ho AD et al. Mobilization of peripheral blood stem cells for autologous transplant in non-Hodgkin's lymphoma and multiple myeloma patients by plerixafor and G-CSF and detection of tumor cell mobilization by PCR in multiple myeloma patients. Bone Marrow Transplant 2010; 45: 269–275.

    Article  CAS  PubMed  Google Scholar 

  99. MacFarland R, Hard ML, Scarborough R, Badel K, Calandra G . A pharmacokinetic study of plerixafor in subjects with varying degrees of renal impairment. Biol Blood Marrow Transplant 2010; 16: 95–101.

    Article  PubMed  Google Scholar 

  100. Douglas KW, Parker AN, Hayden PJ, Rahemtulla A, D'Addio A, Lemoli RM et al. Plerixafor for PBPC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA. Bone Marrow Transplant 2012; 47: 18–23.

    Article  CAS  PubMed  Google Scholar 

  101. Pinto V, Castelli A, Gaidano G, Conconi A . Safe and effective use of plerixafor plus G-CSF in dialysis-dependent renal failure. Am J Hematol 2010; 85: 461–462.

    PubMed  Google Scholar 

  102. Devine SM, Vij R, Rettig M, Todt L, McGlauchlen K, Fisher N et al. Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood 2008; 112: 990–998.

    Article  CAS  PubMed  Google Scholar 

  103. Burroughs L, Mielcarek M, Little MT, Bridger G, Macfarland R, Fricker S et al. Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral-blood mononuclear cells in a canine transplantation model. Blood 2005; 106: 4002–4008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Fruehauf S, Veldwijk MR, Seeger T, Schubert M, Laufs S, Topaly J et al. A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study. Cytotherapy 2009; 11: 992–1001.

    Article  CAS  PubMed  Google Scholar 

  105. Takahashi Y, Tawab AK, Roger E . AMD3100 mobilized apheresis products are rich in T-cells that do not undergo a Th-2 type cytokine polarization: implications for allografting. Blood 2005; 106: 296.

    Article  CAS  Google Scholar 

  106. Pelus LM . Peripheral blood stem cell mobilization: new regimens, new cells, where do we stand. Curr Opin Hematol 2008; 15: 285–292.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Brunner S, Theiss HD, Murr A, Negele T, Franz WM . Primary hyperparathyroidism is associated with increased circulating bone marrow-derived progenitor cells. Am J Physiol Endocrinol Metab 2007; 293: E1670–E1675.

    Article  CAS  PubMed  Google Scholar 

  108. Brunner S, Zaruba MM, Huber B, David RM, Vallaster M, Assmann G et al. Parathyroid hormone effectively induces mobilization of progenitor cells without depletion of bone marrow. Exp Hematol 2008; 36: 1157–1166.

    Article  CAS  PubMed  Google Scholar 

  109. Ballen KK, Shpall EJ, Avigan D, Yeap BY, Fisher DC, McDermott K et al. Phase I trial of parathyroid hormone to facilitate stem cell mobilization. Biol Blood Marrow Transplant 2007; 13: 838–843.

    Article  CAS  PubMed  Google Scholar 

  110. Zohren F, Toutzaris D, Klärner V, Hartung HP, Kieseier B, Haas R . The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans. Blood 2008; 111: 3893–3895.

    Article  CAS  PubMed  Google Scholar 

  111. Bonig H, Watts KL, Chang KH, Kiem HP, Papayannopoulou T . Concurrent blockade of alpha4-integrin and CXCR4 in hematopoietic stem/progenitor cell mobilization. Stem Cells 2009; 27: 836–837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Ramirez P, Rettig MP, Uy GL, Deych E, Holt MS, Ritchey JK et al. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood 2009; 114: 1340–1343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Carlo-Stella C, Di Nicola M, Milani R, Guidetti A, Magni M, Milanesi M et al. Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+ cells in poor mobilizers. Blood 2004; 103: 3287–3295.

    Article  CAS  PubMed  Google Scholar 

  114. Herbert KE, Walkley CR, Winkler IG, Hendy J, Olsen GH, Yuan YD et al. Granulocyte colony-stimulating factor and an RARalpha specific agonist, VTP195183, synergize to enhance the mobilization of hematopoietic progenitor cells. Transplantation 2007; 83: 375–384.

    Article  CAS  PubMed  Google Scholar 

  115. Herbert KE, True S, McArthur G, Prince HM . Safety and efficacy of combining ATRA with G-CSF in HSPC mobilization; a pilot study in multiple myeloma and non-Hodgkin's lymphoma patients. Bone Marrow Transplant 2007; 40: 801–803.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Stem Cell Transplantation, School of Medicine, Ankara University, Ankara, Turkey

    Ş M Bakanay & T Demirer

Authors
  1. Ş M Bakanay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Demirer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Demirer.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bakanay, Ş., Demirer, T. Novel agents and approaches for stem cell mobilization in normal donors and patients. Bone Marrow Transplant 47, 1154–1163 (2012). https://doi.org/10.1038/bmt.2011.170

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.170

Keywords

This article is cited by

Search

Advanced search

Quick links