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Stem Cell Collection

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 Transplantation volume 41, pages 331–338 (2008)Cite this article

Abstract

AMD3100 given with G-CSF has been shown to mobilize CD34+ cells in non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), and Hodgkin's disease (HD) patients who could not collect sufficient cells for autologous transplant following other mobilization regimens. These poor mobilizers are usually excluded from company-sponsored trials, but have been included in an AMD3100 Single Patient Use protocol, referred to as a Compassionate Use Protocol (CUP). A cohort of 115 data-audited poor mobilizers in CUP was assessed, with the objective being to collect ⩾2 × 106 CD34+ cells per kg following AMD3100 plus G-CSF mobilization. The rates of successful CD34+ cell collection were similar for patients who previously failed chemotherapy mobilization or cytokine-only mobilization: NHL—60.3%, MM—71.4% and HD—76.5%. Following transplant, median times to neutrophil and PLT engraftment were 11 days and 18 days, respectively. Engraftment was durable. There were no drug-related serious adverse events. Of the adverse events considered related to AMD3100, two (1.6%) were severe (one patient—headache, one patient—nightmares). Other AMD3100-related adverse events were mild (84.8%) or moderate (13.6%). The most common AMD3100-related adverse events were gastrointestinal reactions, injection site reactions and paresthesias. AMD3100 plus G-CSF offers a new treatment to collect CD34+ cells for autologous transplant from poor mobilizers, with a high success rate.

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References

  1. Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC . The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997; 185: 111–120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lapidot T . Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice. The role of SDF-1/CXCR4 interactions. Ann NY Acad Sci 2001; 938: 83–95.

    Article  CAS  PubMed  Google Scholar 

  3. Shen W, Bendall LJ, Gottlieb DJ, Bradstock KF . The chemokine receptor CXCR4 enhances integrin-mediated in vitro adhesion and facilitates engraftment of leukemic precursor-B cells in the bone marrow. Exp Hematol 2001; 29: 1439–1447.

    Article  CAS  PubMed  Google Scholar 

  4. Sanz-Rodriguez F, Hidalgo A, Teixido J . Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin- mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. Blood 2001; 97: 346–351.

    Article  CAS  PubMed  Google Scholar 

  5. Lapidot T, Petit I . Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 2002; 30: 973–981.

    Article  CAS  PubMed  Google Scholar 

  6. Thomas J, Liu F, Link DC . Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor. Curr Opin Hematol 2002; 9: 183–189.

    Article  PubMed  Google Scholar 

  7. Liles WC, Broxmeyer HE, Rodger E, Wood B, Hubel 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 

  8. 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 

  9. 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 

  10. 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 

  11. Cashen AF, Calandra G, MacFarland R, Lopez S, DiPersio J . A mobilizing regimen of AMD3100+G-CSF increases stem cell collection in patients with Hodgkin's disease, and PK is similar to that of non-cancer patients. Blood (ASH Annual Meeting Abstracts) 2006; 108: 869a; Abstract 3053.

    Google Scholar 

  12. Burger M, Hartmann T, Krome M, Rawluk J, Tamamura H, Fujii N et al. Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Blood 2005; 106: 1824–1830.

    Article  CAS  PubMed  Google Scholar 

  13. Nervi B, Holt M, Rettig MP, Bridger G, Ley TJ, DiPersio JF . AMD3100 mobilizes acute promyelocytic leukemia cells from the bone marrow into the peripheral blood and sensitizes leukemia cells to chemotherapy. Blood (ASH Annual Meeting Abstracts) 2005; 106: 127a; Abstract 246.

    Google Scholar 

  14. 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: 176a; Abstract 568.

    Google Scholar 

  15. Fassas A, Fox M, Calandra G, Tricot G . Successful mobilization of peripheral blood stem cells (PBSCs) with AMD3100 in patients failing to collect with hematopoietic growth factors (HGF) and/or chemotherapy. J Clin Oncol (Meeting Abstracts) 2004; 22 (14 Suppl): 591; Abstract 6643.

    Google Scholar 

  16. Calandra G, Garelik JP, Kohler PT, Brown KR . Problems and benefits of an antibiotic compassionate therapy program. Rev Infect Dis 1987; 9: 1095–1101.

    Article  CAS  PubMed  Google Scholar 

  17. 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 

  18. Lefrere F, Levy V, Makke J, Audat F, Cavazzana-Calvo M, Miclea JM . Successful peripheral blood stem cell harvesting with granulocyte colony-stimulating factor alone after previous mobilization failure. Haematologica 2004; 89: 1532–1534.

    PubMed  Google Scholar 

  19. Goterris R, Hernandez-Boluda JC, Teruel A, Gomez C, Lis MJ, Terol MJ et al. Impact of different strategies of second-line stem cell harvest on the outcome of autologous transplantation in poor peripheral blood stem cell mobilizers. Bone Marrow Transplant 2005; 36: 847–853.

    Article  CAS  PubMed  Google Scholar 

  20. Weaver CH, Tauer K, Zhen B, Schwartzberg LS, Hazelton B, Weaver Z et al. Second attempts at mobilization of peripheral blood stem cells in patients with initial low CD34+ cell yields. J Hematother 1998; 7: 241–249.

    Article  CAS  PubMed  Google Scholar 

  21. Stiff P, Micallef I, McCarthy P, Magalhaes-Silverman M, Flomenberg N, Weisdorf D et al. AMD3100 combined with standard doses of G-CSF leads to rapid, consistent mobilization of hematopoietic progenitor cells in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma. Blood (ASH Annual Meeting Abstracts) 2004; 104: 778a; Abstract 2847.

    Google Scholar 

  22. Dugan MJ, Akard LP, Thompson JM, Nademanee A, Maziarz RT, Bensinger WI et al. Treatment with AMD3100 in multiple myeloma or non-Hodgkin's lymphoma patients to increase the number of peripheral blood stem cells when given with a mobilizing regimen of chemotherapy and G-CSF. Proceedings of American Society of Hematology 2004; 104: 782a; Abstract 2860.

    Google Scholar 

  23. Ehninger G, Fruehauf S, Hubel K, Platzbecker U, Badel K, Calandra G . Steady state mobilization of autologous blood stem cells using G-CSF and AMD3100 in patients with multiple myeloma (MM). Blood (ASH Annual Meeting Abstracts) 2006; 108: 396b; Abstract 5219.

    Google Scholar 

  24. Murata M, Harada M, Kato S, Takahashi S, Ogawa H, Okamoto S et al. Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors. Bone Marrow Transplant 1999; 24: 1065–1071.

    Article  CAS  PubMed  Google Scholar 

  25. Levesque JP, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ . Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest 2003; 111: 187–196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Stiff PJ . Management strategies for the hard-to-mobilize patient. Bone Marrow Transplant 1999; 23 (Suppl 2): S29–S33.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. AnorMED Corp of Genzyme Corp, Langley, British Columbia, Canada

    G Calandra, S-A Crocker, K Badel, B Grove, A Dye & G Bridger

  2. Department of Internal Medicine, Hematology/Oncology, Virginia Commonwealth University, Richmond, VA, USA

    J McCarty

  3. Blood and Bone Marrow Transplant Clinic, Kansas City Cancer Center, Kansas City, MO, USA

    J McGuirk

  4. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    G Tricot

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  1. G Calandra
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Correspondence to G Calandra.

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Calandra, G., McCarty, J., McGuirk, J. 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 41, 331–338 (2008). https://doi.org/10.1038/sj.bmt.1705908

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