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Progenitor Cell Mobilisation

Progenitor content of autologous grafts: mobilized bone marrow vs mobilized blood

Bone Marrow Transplantation volume 32, pages 575–580 (2003)Cite this article

Summary:

The progenitor content of autologous peripheral blood progenitor and stem cell collections is a major determinant of prompt hematopoietic recovery following autologous stem cell transplantation. We analyzed unstimulated bone marrow (BM) and peripheral blood (PB) apheresis products in comparison to those collected following G-CSF or GM-CSF stimulation. We quantitated their committed (CFU-GM) and primitive (long-term culture-initiating cells, LTC-IC) progenitors in relation to hematologic recovery in 63 patients undergoing autografting for lymphoid malignancies. G-CSF, but not GM-CSF, substantially enriched the committed progenitor content (2.5–3.6-fold) of both PB and BM grafts. G-CSF also enriched the LTC-IC content of BM and PB compared to control grafts. GM-CSF augmented (11.5-fold) the LTC-IC content of stimulated BM, but not GM-CSF-mobilized PB. Neutrophil recovery was substantially quicker in recipients of BM or PB mobilized with G-CSF or GM-CSF. In contrast, red cell and platelet recovery was accelerated in recipients of GM-CSF-stimulated BM (but not PB) and G-CSF-stimulated PB (but not BM). No direct correlation between progenitor dose and hematopoietic recovery for neutrophils, platelets or red cells was observed. Cytokine stimulation can augment the committed and more primitive multilineage progenitor content of BM and PB grafts, to a differing extent. The uncertain relationship with multilineage myeloid recovery emphasizes the limitations in using clonogenic progenitor analyses to assess the adequacy of an autologous graft prior to transplantation.

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References

  1. Gianni AM, Siena S, Bregni M et al. Granulocyte–macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation. Lancet 1989; 2: 580–585.

    Article  CAS  PubMed  Google Scholar 

  2. Siena S, Bregni M, Brando B et al. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Blood 1991; 77: 400.

    CAS  PubMed  Google Scholar 

  3. Siena S, Bregni M, Brando B et al. Circulation of CD34+ hematopoietic stem cells in the peripheral blood of high-dose cyclophosphamide-treated patients: enhancement by intravenous recombinant human granulocyte–macrophage colony-stimulating factor. Blood 1989; 74: 1905.

    CAS  PubMed  Google Scholar 

  4. Chao NJ, Schriber JR, Grimes K et al. Granulocyte colony stimulating factor ‘mobilized’ peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy. Blood 1993; 81: 2031.

    CAS  PubMed  Google Scholar 

  5. Pettengell R, Morgenstern GR, Woll PJ et al. Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis. Blood 1993; 82: 3770.

    CAS  PubMed  Google Scholar 

  6. Peters WP, Rosner G, Ross M et al. Comparative effects of granulocyte–macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy. Blood 1993; 81: 709.

    Google Scholar 

  7. Nademanee A, Sniecinski I, Schmidt GM et al. High-dose therapy followed by autologous peripheral-blood stem cell transplantation for patients with Hodgkin's disease and non-Hodgkin's lymphoma using unprimed and granulocyte colony-stimulating factor mobilized peripheral-blood stem cells. J Clin Oncol 1994; 12: 2175.

    Article  Google Scholar 

  8. Bishop MR, Anderson JR, Jackson JD et al. High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte–macrophage colony-stimulating factor on the autograft. Blood 1994; 83: 610.

    CAS  PubMed  Google Scholar 

  9. van der Wall E, Richel DJ, Holtkamp MJ et al. Bone marrow reconstitution after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation: effect on graft size. Ann Oncol 1994; 5: 795.

    Article  CAS  PubMed  Google Scholar 

  10. Weisdorf DJ, Verfaillie CM, Miller WJ et al. Autologous bone marrow versus non-mobilized peripheral blood stem cell transplantation for lymphoid malignancies: a prospective randomized trial. Am J Hematol 1997; 54: 202–208.

    Article  CAS  PubMed  Google Scholar 

  11. Weisdorf D, Miller J, Verfaillie C et al. Cytokine-primed bone marrow stem cells vs peripheral blood stem cells for autologous transplantation: a randomized comparison of GM-CSF vs G-CSF. Biol Blood Marrow Transplant 1997; 3: 217.

    CAS  PubMed  Google Scholar 

  12. Dicke KA, Hood DL, Arneson M et al. Effects of short-term in vivo administration of G-CSF on bone marrow prior to harvesting. Exp Hematol 1997; 25: 34.

    CAS  PubMed  Google Scholar 

  13. Prosper F, Vanoverbeke K, Stroncek D, Verfaillie CM . Primitive long-term culture initiating cells (LTC-ICs) in granulocyte colony-stimulating factor mobilized peripheral blood progenitor cells have similar potential for ex vivo expansion as primitive LTC-ICs in steady state bone marrow. Blood 1997; 89: 3991–3997.

    CAS  PubMed  Google Scholar 

  14. Ho AD, Young D, Maruyama M et al. Pluripotent and lineage-committed CD34+ subsets in leukapheresis products mobilized by G-CSF, GM-CSF vs, a combination of both. Exp Hematol 1996; 24: 1460.

    CAS  PubMed  Google Scholar 

  15. Elias AD, Ayash L, Anderson KC 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.

    CAS  PubMed  Google Scholar 

  16. Broxmeyer HE, Benninger L, Patel JR et al. Kinetic response of human marrow myeloid progenitor cells to in vitro treatment of patients with granulocyte colony-stimulating factor is different from the response to treatment with granulocyte–macrophage colony-stimulating factor. Exp Hematol 1994; 22: 100.

    CAS  PubMed  Google Scholar 

  17. Fujisaki T, Otsuka T, Harqada M et al. Granulocyte colony-stimulating factor mobilizes primitive hematopoietic stem cells in normal individuals. Bone Marrow Transplant 1995; 16: 57.

    CAS  PubMed  Google Scholar 

  18. Langenmayer I, Weaver C, Buckner CD et al. Engraftment of patients with lymphoid malignancies transplanted with autologous bone marrow, peripheral blood stem cells or both. Bone Marrow Transplant 1995; 15: 2411.

    Google Scholar 

  19. Beyer J, Schwella N, Zingsen 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.

    Article  CAS  PubMed  Google Scholar 

  20. Henon R, Liang H, Beck-Wirth G et al. Comparison of hematopoietic and immune recovery after autologous bone marrow or blood stem cell transplants. Bone Marrow Transplant 1992; 9: 285.

    CAS  PubMed  Google Scholar 

  21. Weaver CH, Hazelton B, Birch R et al. An analysis of engraftment kinetics as a function of CD34 content of peripheral blood progenitor cell collection in 692 patients after the administration of myeloablative chemotherapy. Blood 1995; 86: 3961.

    CAS  PubMed  Google Scholar 

  22. Dreger P, Klöss M, Petersen B et al. Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts. Blood 1995; 86: 3970.

    CAS  PubMed  Google Scholar 

  23. Sutherland HJ, Eaves CJ, Lansforp PM et al. Kinetics of committed and primitive progenitor mobilization after chemotherapy and growth factor treatment and their use in autotransplants. Blood 1994; 83: 3808.

    CAS  PubMed  Google Scholar 

  24. Christ O, Kronenwett R, Haas R, Zoller M . Co. Exp Hematol 2001; 29: 380.

    Article  CAS  PubMed  Google Scholar 

  25. Craddock CF, Nakamoto B, Andrews RG et al. Antibodies to VLA4 integrin mobilized long-term repopulating cells and augment cytokine-induced mobilization in primates. Blood 1997; 90: 4779.

    CAS  PubMed  Google Scholar 

  26. Bender JG, Lum L, Unverzagt KL et al. Correlation of colony-forming cells, long-term culture initiating cells and CD34+ cells in apheresis products from patients mobilized for peripheral blood progenitors with different regimens. Bone Marrow Transplant 1994; 13: 479.

    CAS  PubMed  Google Scholar 

  27. To LB, Dyson PG, Juttner CA . Cell-dose effect in circulating stem cell autografting. Lancet 1986; 2: 404.

    Article  CAS  PubMed  Google Scholar 

  28. Sheridan WP, Begley CG, To LB et al. Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood progenitor cells to restore hematopoiesis after high-dose chemotherapy for lymphoid malignancies. Bone Marrow Transplant 1994; 14: 105.

    CAS  PubMed  Google Scholar 

  29. Bender JG, To LB, Williams S, Schwartzberg LS . Defining a therapeutic dose of peripheral blood stem cells. J Hematother 1992; 1: 329.

    Article  CAS  PubMed  Google Scholar 

  30. Reiffers L, Leverger G, Marit G et al. Hematopoietic reconstitution after autologous blood stem cell transplantation. In: Gale RP, Champlin RE (eds). Bone Marrow Transplantation: Current Controversies. Proceedings of Sandoz-UCLA Symposium. Liss: New York, NY, 1988, p 313.

    Google Scholar 

  31. To LB, Haylock DN, Simmons PJ, Juttner CA . The biology and clinical uses of blood stem cells. Blood 1997; 89: 2233.

    CAS  PubMed  Google Scholar 

  32. Kiss JE, Rybka WB, Winkelstein A et al. Relationship of CD34+ cell dose to early and late hematopoiesis following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 1997; 19: 303.

    Article  CAS  PubMed  Google Scholar 

  33. Haas 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.

    CAS  PubMed  Google Scholar 

  34. Watts MJ, Sullivan AM, Jamieson E et al. Progenitor cells mobilization after low-dose cyclophosphamide and G-CSF: an analysis of progenitor cell quality and factors predicting for these parameters in 101 pre-treated patients with malignant lymphoma. J Clin Oncol 1997; 15: 535.

    Article  CAS  PubMed  Google Scholar 

  35. Hogge DE, Lambie K, Sutherland HJ et al. Quantitation of primitive and lineage-committed progenitors in mobilized peripheral blood for prediction of platelet recovery in post autologous transplant. Bone Marrow Transplant 2000; 25: 589.

    Article  CAS  PubMed  Google Scholar 

  36. Robinson SN, Freedman AS, Neuberg DS et al. Loss of marrow reserve from dose-intensified chemotherapy results in impaired hematopoietic reconstitution after autologous transplantation: CD34+, CD34+38−, and week-6 CAFC assays predict poor engraftment. Exp Hematol 2000; 28: 1325.

    Article  CAS  PubMed  Google Scholar 

  37. Isola L, Scigliaro E, Fruchtman S . Long-term follow-up after allogeneic granulocyte colony stimulating factor-primed bone marrow transplantation. Biol Blood Marrow Transplant 2000; 6: 428.

    Article  CAS  PubMed  Google Scholar 

  38. Schmitz N, Bacigalupo A, Hasenclever D et al. Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with leukaemia: first results of a randomized multicentre trial of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1998; 2: 995.

    Article  Google Scholar 

  39. Champlin RE, Schmitz N, Horowitz MM et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow and Marrow Tansplantation (EBMT). Blood 2000; 95: 3702.

    CAS  PubMed  Google Scholar 

  40. Bensinger WI, Martin PJ, Storer B et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Blood and Marrow Transplant Program and the Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    E Dahl, J Burroughs, T DeFor, C Verfaillie & D Weisdorf

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  1. E Dahl
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  2. J Burroughs
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  3. T DeFor
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  4. C Verfaillie
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  5. D Weisdorf
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Correspondence to D Weisdorf.

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Dahl, E., Burroughs, J., DeFor, T. et al. Progenitor content of autologous grafts: mobilized bone marrow vs mobilized blood. Bone Marrow Transplant 32, 575–580 (2003). https://doi.org/10.1038/sj.bmt.1704237

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