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• W2022700772 abstract "Several stem cell mobilization strategies have been employed in the past 2 decades, including chemotherapy, hematopoietic growth factors, and chemotherapy plus growth factors. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF are standard agents approved for peripheral blood stem cell mobilization since the early 1990s. Between 5% and 20% of patients, however, fail to mobilize a sufficient numbers of peripheral blood stem cells in response to G-CSF with or without chemotherapy. Recent advances in defining the basic mechanisms regulating the interactions between hematopoietic stem cells and their marrow niche had led to the discovery that CXCR4 and stromal-cell−derived factor 1α axis play a significant role. Plerixafor, an antagonist of the CXCR4-stromal-cell−derived factor 1α axis has been shown to result in a significant mobilization of hematopoietic stem cells. Numerous clinical trials have demonstrated that the combination of G-CSF and AMD3100 (G+A) resulted in a significant increase in CD34+ cell yield as compared to the administration of G-CSF alone. In particular, the progenitors mobilized have been shown to comprise a significantly higher proportion of primitive and possibly more potent CD34+/CD38- subpopulation. Transplantation of PBSC mobilized by G+A administration have led to a rapid and sustained neutrophil and platelet engraftment. Another prospective role of this new class of agents might lie in the mobilization of dormant leukemia stem cells that are well protected by the niche. The future role of CXCR4 antagonists in treatment of hematologic malignancies includes mobilization of hematopoietic stem cells for transplantation and mobilization of leukemia-initiating cells for long-term cure. Several stem cell mobilization strategies have been employed in the past 2 decades, including chemotherapy, hematopoietic growth factors, and chemotherapy plus growth factors. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF are standard agents approved for peripheral blood stem cell mobilization since the early 1990s. Between 5% and 20% of patients, however, fail to mobilize a sufficient numbers of peripheral blood stem cells in response to G-CSF with or without chemotherapy. Recent advances in defining the basic mechanisms regulating the interactions between hematopoietic stem cells and their marrow niche had led to the discovery that CXCR4 and stromal-cell−derived factor 1α axis play a significant role. Plerixafor, an antagonist of the CXCR4-stromal-cell−derived factor 1α axis has been shown to result in a significant mobilization of hematopoietic stem cells. Numerous clinical trials have demonstrated that the combination of G-CSF and AMD3100 (G+A) resulted in a significant increase in CD34+ cell yield as compared to the administration of G-CSF alone. In particular, the progenitors mobilized have been shown to comprise a significantly higher proportion of primitive and possibly more potent CD34+/CD38- subpopulation. Transplantation of PBSC mobilized by G+A administration have led to a rapid and sustained neutrophil and platelet engraftment. Another prospective role of this new class of agents might lie in the mobilization of dormant leukemia stem cells that are well protected by the niche. The future role of CXCR4 antagonists in treatment of hematologic malignancies includes mobilization of hematopoietic stem cells for transplantation and mobilization of leukemia-initiating cells for long-term cure. Peripheral blood stem cells (PBSCs) have largely replaced bone marrow (BM)−derived cells in autologous transplants and have become the source of stem cells in the majority of allogeneic transplants. In the mid-1980s, several institutions demonstrated that PBSCs could represent viable alternatives to BM cells as source of hematopoietic stem and progenitor cells for autologous transplantation [1Korbling M. Dorken B. Ho A.D. et al.Autologous transplantation of blood-derived hemopoietic stem cells after myeloablative therapy in a patient with Burkitt’s lymphoma.Blood. 1986; 67: 529-532PubMed Google Scholar, 2Reiffers J. Bernard P. David B. et al.Successful autologous transplantation with peripheral blood hemopoietic cells in a patient with acute leukemia.Exp Hematol. 1986; 14: 312-315PubMed Google Scholar, 3To L.B. Dyson P.G. Branford A.L. et al.Peripheral blood stem cells collected in very early remission produce rapid and sustained autologous haemopoietic reconstitution in acute non-lymphoblastic leukaemia.Bone Marrow Transplant. 1987; 2: 103-108PubMed Google Scholar, 4Bell A.J. Figes A. Oscier D.G. Hamblin T.J. Peripheral blood stem cell autografts in the treatment of lymphoid malignancies: initial experience in three patients.Br J Haematol. 1987; 66: 63-68Crossref PubMed Scopus (29) Google Scholar, 5Kessinger A. Armitage J.O. Landmark J.D. Smith D.M. Weisenburger D.D. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy.Blood. 1988; 71: 723-727PubMed Google Scholar]. Use of PBSCs offers several advantages, such as harvest of cells without general anesthesia, elimination of pain resulting from multiple aspirations from the BM, and it is associated with more rapid engraftment [6Beyer J. Schwella N. Zingsem J. et al.Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison.J Clin Oncol. 1995; 13: 1328-1335Crossref PubMed Scopus (283) Google Scholar, 7Schmitz N. Linch D.C. Dreger P. et al.Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients.Lancet. 1996; 347: 353-357Abstract PubMed Scopus (537) Google Scholar, 8Hartmann O. Le Corroller A.G. Blaise D. et al.Peripheral blood stem cell and bone marrow transplantation for solid tumors and lymphomas: hematologic recovery and costs. A randomized, controlled trial.Ann Intern Med. 1997; 126: 600-607Crossref PubMed Scopus (250) Google Scholar]. The main challenge of PBSCs is that they exist in the circulation in very small numbers. Hematopoietic progenitor and stem cells (HSCs) reside in the BM and have to be mobilized into the circulation before being collected by apheresis. The number of apheresis procedures needed and the success of transplantation are determined by the efficiency of stem cell mobilization [9Weaver C.H. Hazelton B. Birch R. et al.An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy.Blood. 1995; 86: 3961-3969PubMed Google Scholar, 10Bensinger W. Appelbaum F. Rowley S. et al.Factors that influence collection and engraftment of autologous peripheral-blood stem cells.J Clin Oncol. 1995; 13: 2547-2555Crossref PubMed Scopus (627) Google Scholar] (reviewed in reference [11To L.B. Haylock D.N. Simmons P.J. Juttner C.A. The biology and clinical uses of blood stem cells.Blood. 1997; 89: 2233-2258Crossref PubMed Google Scholar]). Stem cells adhere to their BM niche by interactions between stromal-cell−derived factor 1α (SDF-1α), which is produced by BM stromal cells, and CXCR4, which is expressed on CD34+ cells [12Mohle R. Bautz F. Rafii S. et al.The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1.Blood. 1998; 91: 4523-4530Crossref PubMed Google Scholar, 13Lapidot 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: 973-981Abstract Full Text Full Text PDF PubMed Scopus (691) Google Scholar]. Granulocyte colony-stimulating factor (G-CSF), the standard and most widely used agent for this purpose during the past 20 years, mobilizes stem cells from the marrow niche by secretion of neutrophil-associated extracellular proteases, such as matrix metalloproteinase-9, which subsequently releases HSCs from their niche [14Petit I. Szyper-Kravitz M. Nagler A. et al.G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4.Nat Immunol. 2002; 3: 687-694Crossref PubMed Scopus (1128) Google Scholar]. On the other hand, Plerixafor, a novel mobilization agent, can directly inhibit the CXCR4−SDF1-α cell-to-cell interaction [15Broxmeyer H.E. Orschell C.M. Clapp D.W. et al.Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist.J Exp Med. 2005; 201: 1307-1318Crossref PubMed Scopus (891) Google Scholar, 16Cashen A.F. Nervi B. DiPersio J. AMD3100: CXCR4 antagonist and rapid stem cell-mobilizing agent.Future Oncol. 2007; 3: 19-27Crossref PubMed Scopus (72) Google Scholar]. This agent has, in the meantime, been demonstrated to mobilize quantitatively a larger amount of CD34+ cells in patients who have failed to yield an adequate amount upon mobilization attempts with G-CSF with or without chemotherapy. Thus, Plerixafor has been approved both in North America and in Europe and represents a milestone in the development of PBSC transplantations. This article will review the history and physiology of HSC mobilization and will provide recommendations on the use of Plerixafor in daily clinical practice. Until the mid-1980s, BM was the only source of HSCs for allogeneic or autologous transplantations. In the second half of the 1980s, several groups had shown that stem cells could be harvested from the peripheral blood after chemotherapy. Myelosuppressive drugs induced a significant increase in the number of PBSCs during the recovery phase [1Korbling M. Dorken B. Ho A.D. et al.Autologous transplantation of blood-derived hemopoietic stem cells after myeloablative therapy in a patient with Burkitt’s lymphoma.Blood. 1986; 67: 529-532PubMed Google Scholar, 2Reiffers J. Bernard P. David B. et al.Successful autologous transplantation with peripheral blood hemopoietic cells in a patient with acute leukemia.Exp Hematol. 1986; 14: 312-315PubMed Google Scholar, 3To L.B. Dyson P.G. Branford A.L. et al.Peripheral blood stem cells collected in very early remission produce rapid and sustained autologous haemopoietic reconstitution in acute non-lymphoblastic leukaemia.Bone Marrow Transplant. 1987; 2: 103-108PubMed Google Scholar, 4Bell A.J. Figes A. Oscier D.G. Hamblin T.J. Peripheral blood stem cell autografts in the treatment of lymphoid malignancies: initial experience in three patients.Br J Haematol. 1987; 66: 63-68Crossref PubMed Scopus (29) Google Scholar, 5Kessinger A. Armitage J.O. Landmark J.D. Smith D.M. Weisenburger D.D. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy.Blood. 1988; 71: 723-727PubMed Google Scholar]. The yield was, however, unpredictable and most patients had to undergo up to six leukapheresis procedures before an adequate amount was collected. The availability of granulocyte macrophage (GM)-CSF and G-CSF has revolutionized the mobilization of PBSCs for transplantation. In the meantime, PBSCs have largely replaced BM in autologous stem cell transplants (autoSCT). The latter has been used successfully to induce long-term cure in patients with refractory or recurrent non-Hodgkin’s lymphoma (NHL) [17Philip T. Armitage J.O. Spitzer G. et al.High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin’s lymphoma.N Engl J Med. 1987; 316: 1493-1498Crossref PubMed Scopus (692) Google Scholar, 18Rohatiner A.Z. Nadler L. Davies A.J. et al.Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up.J Clin Oncol. 2007; 25: 2554-2559Crossref PubMed Scopus (194) Google Scholar]. Treatment-related mortality rate for autoSCT is <5%. The low rate of early transplantation-associated mortality must, however, be balanced with potential contamination of the autologous stem cell graft with tumor cells. Risk of myelodysplasia/acute myeloid leukemia associated with the conditioning regimens must also be considered. AutoSCT has also become the standard of care after induction chemotherapy for younger and more fit patients (younger than 65 to 70 years old) with multiple myeloma (MM) [19Attal M. Harousseau J.L. Stoppa A.M. et al.A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome.N Engl J Med. 1996; 335: 91-97Crossref PubMed Scopus (2569) Google Scholar]. Several clinical trials comparing conventional chemotherapy with high-dose chemotherapy/autoSCT have shown improved outcomes in patients who received autoSCT as primary treatment [19Attal M. Harousseau J.L. Stoppa A.M. et al.A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome.N Engl J Med. 1996; 335: 91-97Crossref PubMed Scopus (2569) Google Scholar, 20Child J.A. Morgan G.J. Davies F.E. et al.High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma.N Engl J Med. 2003; 348: 1875-1883Crossref PubMed Scopus (1574) Google Scholar]. PBSCs have also become the source of stem cells in a large number of allogeneic transplantations. Use of PBSCs offers several advantages, such as harvest of cells without general anesthesia, elimination of pain after multiple aspirations from the BM, and most important, it is associated with more rapid engraftment [21Juttner C.A. To L.B. Ho J.Q. et al.Early lympho-hemopoietic recovery after autografting using peripheral blood stem cells in acute non-lymphoblastic leukemia.Transplant Proc. 1988; 20: 40-42PubMed Google Scholar, 22Corringham R.E. Ho A.D. Rapid and sustained allogeneic transplantation using immunoselected CD34(+)-selected peripheral blood progenitor cells mobilized by recombinant granulocyte- and granulocyte-macrophage colony-stimulating factors.Blood. 1995; 86: 2052-2054PubMed Google Scholar, 23Korbling M. Anderlini P. Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter?.Blood. 2001; 98: 2900-2908Crossref PubMed Scopus (281) Google Scholar]. The main disadvantage of PBSCs is that they exist in the circulation in very small numbers. Fewer than 0.05% of white blood cells are CD34(+), which is a cell surface protein that is expressed on hematopoietic stem and progenitor cells and represents a reliable surrogate marker for the presence of progenitor cells responsible for reconstitution after transplantation [24Civin C.I. Strauss L.C. Brovall C. et al.Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells.J Immunol. 1984; 133: 157-165PubMed Google Scholar]. As mentioned here, HSCs are mainly found in the BM and have to be mobilized into the circulation before collection. The number of apheresis procedures needed and the success of transplantations are determined by the efficiency of stem cell mobilization. In the early days of autoSCT, stem cell mobilization was achieved with chemotherapeutic drugs, as chemotherapy induces a significant increase in the number of HSCs in circulating blood at the time of recovery [1Korbling M. Dorken B. Ho A.D. et al.Autologous transplantation of blood-derived hemopoietic stem cells after myeloablative therapy in a patient with Burkitt’s lymphoma.Blood. 1986; 67: 529-532PubMed Google Scholar, 3To L.B. Dyson P.G. Branford A.L. et al.Peripheral blood stem cells collected in very early remission produce rapid and sustained autologous haemopoietic reconstitution in acute non-lymphoblastic leukaemia.Bone Marrow Transplant. 1987; 2: 103-108PubMed Google Scholar, 5Kessinger A. Armitage J.O. Landmark J.D. Smith D.M. Weisenburger D.D. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy.Blood. 1988; 71: 723-727PubMed Google Scholar]. However, many patients also failed to mobilize sufficient PBSCs for transplantation in response to chemotherapy. The availability of GM-CSF and G-CSF has significantly changed the spectrum of PBSCs mobilization (for a detailed review, see reference [11To L.B. Haylock D.N. Simmons P.J. Juttner C.A. The biology and clinical uses of blood stem cells.Blood. 1997; 89: 2233-2258Crossref PubMed Google Scholar]). Indeed, in the late 1980s, GM-CSF and G-CSF were made available [25Gianni A.M. Siena S. Bregni M. et al.Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation.Lancet. 1989; 2: 580-585Abstract PubMed Scopus (671) Google Scholar, 26Haas R. Ho A.D. Bredthauer U. et al.Successful autologous transplantation of blood stem cells mobilized with recombinant human granulocyte-macrophage colony-stimulating factor.Exp Hematol. 1990; 18: 94-98PubMed Google Scholar, 27Elias A.D. Ayash L. Anderson K.C. et al.Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer.Blood. 1992; 79: 3036-3044PubMed Google Scholar, 28Bensinger W. Singer J. Appelbaum F. et al.Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor.Blood. 1993; 81: 3158-3163PubMed Google Scholar]. G-CSF and GM-CSF were approved for use as HSC-mobilizing agents, but G-CSF (in combination with chemotherapy or alone) has become the standard. Unfortunately, some patients, especially those who have been heavily pretreated with chemotherapy or irradiation, still fail to mobilize sufficient numbers of PBSCs for transplantation in response to G-CSF with or without chemotherapy [29Haas R. Mohle R. Fruhauf S. et al.Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma.Blood. 1994; 83: 3787-3794PubMed Google Scholar, 30Sugrue M.W. Williams K. Pollock B.H. et al.Characterization and outcome of “hard to mobilize” lymphoma patients undergoing autologous stem cell transplantation.Leuk Lymphoma. 2000; 39: 509-519Crossref PubMed Scopus (73) Google Scholar, 31Tarella C. Di Nicola M. Caracciolo D. 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: 725-732Crossref PubMed Scopus (44) Google Scholar, 32Gordan L.N. Sugrue M.W. Lynch J.W. et al.Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation.Leuk Lymphoma. 2003; 44: 815-820Crossref PubMed Scopus (79) Google Scholar, 33Kuittinen T. Nousiainen T. Halonen P. Mahlamaki E. Jantunen E. Prediction of mobilisation failure in patients with non-Hodgkin’s lymphoma.Bone Marrow Transplant. 2004; 33: 907-912Crossref PubMed Scopus (104) Google Scholar]. There were numerous reports on patients who failed to mobilize sufficient numbers of PBSCs for transplantation [30Sugrue M.W. Williams K. Pollock B.H. et al.Characterization and outcome of “hard to mobilize” lymphoma patients undergoing autologous stem cell transplantation.Leuk Lymphoma. 2000; 39: 509-519Crossref PubMed Scopus (73) Google Scholar, 31Tarella C. Di Nicola M. Caracciolo D. 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: 725-732Crossref PubMed Scopus (44) Google Scholar, 32Gordan L.N. Sugrue M.W. Lynch J.W. et al.Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation.Leuk Lymphoma. 2003; 44: 815-820Crossref PubMed Scopus (79) Google Scholar, 33Kuittinen T. Nousiainen T. Halonen P. Mahlamaki E. Jantunen E. Prediction of mobilisation failure in patients with non-Hodgkin’s lymphoma.Bone Marrow Transplant. 2004; 33: 907-912Crossref PubMed Scopus (104) Google Scholar, 34Pavone V. Gaudio F. Console G. et al.Poor mobilization is an independent prognostic factor in patients with malignant lymphomas treated by peripheral blood stem cell transplantation.Bone Marrow Transplant. 2006; 37: 719-724Crossref PubMed Scopus (90) Google Scholar, 35Akhtar S. Weshi A.E. Rahal M. et al.Factors affecting autologous peripheral blood stem cell collection in patients with relapsed or refractory diffuse large cell lymphoma and Hodgkin lymphoma: a single institution result of 168 patients.Leuk Lymphoma. 2008; 49: 769-778Crossref PubMed Scopus (54) Google Scholar, 36Pusic I. Jiang S.Y. Landua S. et al.Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation.Biol Blood Marrow Transplant. 2008; 14: 1045-1056Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar, 37Hosing C. Saliba R.M. Ahlawat S. et al.Poor hematopoietic stem cell mobilizers: a single institution study of incidence and risk factors in patients with recurrent or relapsed lymphoma.Am J Hematol. 2009; 84: 335-337Crossref PubMed Scopus (83) Google Scholar]. The incidence has been reported to range from 5% to 40% [31Tarella C. Di Nicola M. Caracciolo D. 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: 725-732Crossref PubMed Scopus (44) Google Scholar, 32Gordan L.N. Sugrue M.W. Lynch J.W. et al.Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation.Leuk Lymphoma. 2003; 44: 815-820Crossref PubMed Scopus (79) Google Scholar, 33Kuittinen T. Nousiainen T. Halonen P. Mahlamaki E. Jantunen E. Prediction of mobilisation failure in patients with non-Hodgkin’s lymphoma.Bone Marrow Transplant. 2004; 33: 907-912Crossref PubMed Scopus (104) Google Scholar, 34Pavone V. Gaudio F. Console G. et al.Poor mobilization is an independent prognostic factor in patients with malignant lymphomas treated by peripheral blood stem cell transplantation.Bone Marrow Transplant. 2006; 37: 719-724Crossref PubMed Scopus (90) Google Scholar, 35Akhtar S. Weshi A.E. Rahal M. et al.Factors affecting autologous peripheral blood stem cell collection in patients with relapsed or refractory diffuse large cell lymphoma and Hodgkin lymphoma: a single institution result of 168 patients.Leuk Lymphoma. 2008; 49: 769-778Crossref PubMed Scopus (54) Google Scholar, 36Pusic I. Jiang S.Y. Landua S. et al.Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation.Biol Blood Marrow Transplant. 2008; 14: 1045-1056Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar, 37Hosing C. Saliba R.M. Ahlawat S. et al.Poor hematopoietic stem cell mobilizers: a single institution study of incidence and risk factors in patients with recurrent or relapsed lymphoma.Am J Hematol. 2009; 84: 335-337Crossref PubMed Scopus (83) Google Scholar]. Thus far, there is no consensus on the definition of poor mobilizers. Some reports used a value of 1.0 × 106 CD34+ cells/kg body weight (BW), whereas others used a threshold of 2.0 × 106 CD34+ cells/kg BW [32Gordan L.N. Sugrue M.W. Lynch J.W. et al.Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation.Leuk Lymphoma. 2003; 44: 815-820Crossref PubMed Scopus (79) Google Scholar, 33Kuittinen T. Nousiainen T. Halonen P. Mahlamaki E. Jantunen E. Prediction of mobilisation failure in patients with non-Hodgkin’s lymphoma.Bone Marrow Transplant. 2004; 33: 907-912Crossref PubMed Scopus (104) Google Scholar, 34Pavone V. Gaudio F. Console G. et al.Poor mobilization is an independent prognostic factor in patients with malignant lymphomas treated by peripheral blood stem cell transplantation.Bone Marrow Transplant. 2006; 37: 719-724Crossref PubMed Scopus (90) Google Scholar, 35Akhtar S. Weshi A.E. Rahal M. et al.Factors affecting autologous peripheral blood stem cell collection in patients with relapsed or refractory diffuse large cell lymphoma and Hodgkin lymphoma: a single institution result of 168 patients.Leuk Lymphoma. 2008; 49: 769-778Crossref PubMed Scopus (54) Google Scholar, 36Pusic I. Jiang S.Y. Landua S. et al.Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation.Biol Blood Marrow Transplant. 2008; 14: 1045-1056Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar, 37Hosing C. Saliba R.M. Ahlawat S. et al.Poor hematopoietic stem cell mobilizers: a single institution study of incidence and risk factors in patients with recurrent or relapsed lymphoma.Am J Hematol. 2009; 84: 335-337Crossref PubMed Scopus (83) Google Scholar], as a measurable parameter for poor mobilization. Most recent studies have adopted the definition of poor mobilization as inability to collect 2.0 × 106 cells/kg BW CD34+ cells. This can obviously only be estimated retrospectively after leukapheresis has been performed. There was also no clear-cut stipulation on the number of leukapheresis procedures required to achieve this goal as a parameter to distinguish good mobilizers from poor mobilizers. We have previously shown that there is a highly significant correlation between the CD34+ concentration in peripheral blood and the potential to collect an adequate amount of CD34+ cells within one or up to three leukapheresis procedures [38Fruehauf S. Haas R. Conradt C. et al.Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy.Blood. 1995; 85: 2619-2626PubMed Google Scholar, 39Fruehauf S. Schmitt K. Veldwijk M.R. et al.Peripheral blood progenitor cell (PBPC) counts during steady-state haemopoiesis enable the estimation of the yield of mobilized PBPC after granulocyte colony-stimulating factor supported cytotoxic chemotherapy: an update on 100 patients.Br J Haematol. 1999; 105: 786-794Crossref PubMed Scopus (39) Google Scholar]. Given the current advances in development of standards and guidelines for quality control of PBSC products, there is an increasing need for a better definition of poor mobilization. Based on previous reports and a retrospective analysis of 840 patients at the Heidelberg Center who were mobilized with chemotherapy and growth factors with the intent of autologous transplantation, we have confirmed previous observations that preapheresis CD34+ count reliably predicts the quality of collection. As reported in the literature, many groups have suggested that a peak level of 20/μL CD34+ cells should be considered as the threshold. Of the 840 patients with MM and NHL scheduled to receive autologous transplants, 129 patients (15.3%) had preapheresis CD34+ counts of <20/μL and were considered to be poor mobilizers. Among them, 38 patients (4.5%) had CD34+ levels between 11 and 19/μL at maximum stimulation, defined as “borderline” poor mobilizers, 49 patients (5.8%) had CD34+ levels between 6 and 10/μL, defined as “relative” poor mobilizers, and 42 patients (5.0%) had levels <5/μL, defined as “absolute” poor mobilizers. Another controversial issue is whether higher concentrations of CD34+ cells transplanted would produce better long-term outcomes. Current evidence indicates that once an adequate amount has been stimulated, CD34+ cell numbers >2.0 × 106 cells/kg BW CD34+ cells would not necessarily confer more advantage in terms of engraftment of leukocytes and platelets. Our previous observation showed that although higher doses of CD34+ cells (i.e., >6.5 × 106/kg BW) might marginally but significantly shorten the time to leukocyte and platelet recovery, stable engraftment was achieved with transplantation of 2.0 × 106 CD34+ cells/kg BW. Thus, there is no solid evidence that for autologous transplant, levels of >5.0 to 6.0 × 106/kg BW would improve long-term clinical outcomes. The most primitive CD34+ cells are maintained in the marrow niche by binding to cellular determinants through a number of adhesion molecules. Although multiple adhesive interactions are known that mediate the attachment of HSCs to the extracellular matrix and stromal cells of the BM (for a complete review see reference [40Ho A.D. Wagner W. The beauty of asymmetry: asymmetric divisions and self-renewal in the haematopoietic system.Curr Opin Hematol. 2007; 14: 330-336Crossref PubMed Scopus (45) Google Scholar]). Of these, the binding of the SDF-1 chemokine (chemokine [C-X-C motif] ligand 12; CXL-12) located on the surface of BM stromal cells and osteoclasts to its receptor, CXCR4, located on the surface of CD34+ cells, has emerged as an essential signal for HSC trafficking to and from the BM [14Petit I. Szyper-Kravitz M. Nagler A. et al.G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4.Nat Immunol. 2002; 3: 687-694Crossref PubMed Scopus (1128) Google Scholar]. Experiments with neutralizing antibodies directed against CXCR4 or SDF-1 showed that uncoupling of SDF-1/CXCR4 signaling is a crucial step in G-CSF−mediated HSC mobilization. Plerixafor, an inhibitor of CXCR4/SDF" @default.
• W2022700772 created "2016-06-24" @default.
• W2022700772 creator A5020996390 @default.
• W2022700772 creator A5067574718 @default.
• W2022700772 date "2011-07-01" @default.
• W2022700772 modified "2023-10-08" @default.
• W2022700772 title "In and out of the niche: perspectives in mobilization of hematopoietic stem cells" @default.
• W2022700772 cites W120762819 @default.
• W2022700772 cites W1504660023 @default.
• W2022700772 cites W1548997088 @default.
• W2022700772 cites W160332237 @default.
• W2022700772 cites W1879666912 @default.
• W2022700772 cites W1880227053 @default.
• W2022700772 cites W1881943990 @default.
• W2022700772 cites W1969881698 @default.
• W2022700772 cites W1978321902 @default.
• W2022700772 cites W1988224129 @default.
• W2022700772 cites W1991500911 @default.
• W2022700772 cites W2009299193 @default.
• W2022700772 cites W2010193429 @default.
• W2022700772 cites W2015418232 @default.
• W2022700772 cites W2018519445 @default.
• W2022700772 cites W2019381460 @default.
• W2022700772 cites W2020751729 @default.
• W2022700772 cites W2020806642 @default.
• W2022700772 cites W2022271217 @default.
• W2022700772 cites W2024835620 @default.
• W2022700772 cites W2031221162 @default.
• W2022700772 cites W2034747844 @default.
• W2022700772 cites W2051497664 @default.
• W2022700772 cites W2063809730 @default.
• W2022700772 cites W2074468909 @default.
• W2022700772 cites W2075884310 @default.
• W2022700772 cites W2078814808 @default.
• W2022700772 cites W2081672307 @default.
• W2022700772 cites W2085269642 @default.
• W2022700772 cites W2102591890 @default.
• W2022700772 cites W2105390322 @default.
• W2022700772 cites W2114805956 @default.
• W2022700772 cites W2121413131 @default.
• W2022700772 cites W2124090816 @default.
• W2022700772 cites W2124514001 @default.
• W2022700772 cites W2125887123 @default.
• W2022700772 cites W2127678757 @default.
• W2022700772 cites W2131311832 @default.
• W2022700772 cites W2158424965 @default.
• W2022700772 cites W2163065691 @default.
• W2022700772 cites W2298694094 @default.
• W2022700772 cites W2313423582 @default.
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