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Collection of hematopoietic stem cells from patients with autoimmune diseases

Bone Marrow Transplantation volume 28, pages 1–12 (2001)Cite this article

Abstract

We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 μg/kg/day) or cyclophosphamide (2 or 4 g/m2) with either G-CSF (5 or 10 μg/kg/day) or GM-CSF (5 μg/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P < 0.001). G-CSF alone was more likely to cause disease exacerbation than the combination of cyclophosphamide and G-CSF (P = 0.003). Three patients died as a result of cyclophosphamide-based stem cell collection (2.6% of patients mobilized with cyclophosphamide). When corrected for patient weight and apheresis volume, progenitor cell yields tended to vary by underlying disease, prior medication history and mobilization regimen. Trends in the approaches to, and results of, progenitor cell mobilization are suggested by this survey. While cytokine-based mobilization appears less toxic, it is more likely to result in disease reactivation. Optimization with regard to cell yields and safety are likely to be disease-specific and prospective disease-specific studies of mobilization procedures appear warranted. Bone Marrow Transplantation (2001) 28, 1–12.

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References

  1. Burt RK, Burns WH, Miller SD . Bone marrow transplantation for multiple sclerosis: returning to Pandora's box Immunol Today 1997 18: 559–561

    Article  CAS  Google Scholar 

  2. Burt RK . BMT for severe autoimmune diseases: an idea whose time has come Oncology 1997 11: 1001–1014; 1017, discussion 1018–1024

    Google Scholar 

  3. Snowden JA, Brooks PM, Biggs JC . Haemopoietic stem cell transplantation for autoimmune diseases Br J Haematol 1997 99: 9–22

    Article  CAS  Google Scholar 

  4. Tyndall A, Gratwohl A . Hemopoietic blood and marrow transplants in the treatment of severe autoimmune disease Curr Opin Hematol 1997 4: 390–394

    Article  CAS  Google Scholar 

  5. Ikehara S . Bone marrow transplantation for autoimmune diseases Acta Haematologica 1998 99: 116–132

    Article  CAS  Google Scholar 

  6. Marmont AM . Stem cell transplantation for severe autoimmune diseases: progress and problems Haematologica 1998 83: 733–743

    CAS  Google Scholar 

  7. Burt RK, Traynor A . Hematopoietic stem cell therapy of autoimmune diseases Curr Opin Hematol 1998 5: 472–477

    Article  CAS  Google Scholar 

  8. Marmont AM . New horizons in the treatment of autoimmune diseases: immunoablation and stem cell transplantation Annu Rev Med 2000 51: 115–134

    Article  CAS  Google Scholar 

  9. Burt RK, Traynor AE, Pope R et al. Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation Blood 1998 92: 3505—3514

    Google Scholar 

  10. Burt RK, Traynor AE, Cohen B et al. T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients Bone Marrow Transplant 1998 21: 537–541

    Article  CAS  Google Scholar 

  11. Fassas A, Anagnostopoulos A, Kazis A et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first result of a pilot study Bone Marrow Transplant 1997 20: 631–638

    Article  CAS  Google Scholar 

  12. Kozak T, Havrdova E, Pit'ha J et al. High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis Bone Marrow Transplant 2000 25: 525–531

    Article  CAS  Google Scholar 

  13. Fassas A, Anagnostopoulos A, Kazis A et al. Autologous stem cell transplantation in progressive multiple sclerosis – an interim analysis of efficacy J Clin Immunol 2000 20: 24–30

    Article  CAS  Google Scholar 

  14. Burt RK, Georganas C, Schroeder J et al. Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients Arthr Rheum 1999 42: 2281–2285

    Article  CAS  Google Scholar 

  15. Snowden JA, Biggs JC, Milliken ST et al. A phase I/II dose escalation study of intensified cyclophosphamide and autologous blood stem cell rescue in severe, active rheumatoid arthritis Arthr Rheum 1999 42: 2286–2292

    Article  CAS  Google Scholar 

  16. Durez P, Toungouz M, Schandene L et al. Remission and immune reconstitution after T-cell-depleted stem-cell transplantation for rheumatoid arthritis Lancet 1998 352: 881

    Article  CAS  Google Scholar 

  17. McColl G, Kohsaka H, Szer J, Wicks I . High-dose chemotherapy and syngeneic hemopoietic stem-cell transplantation for severe, seronegative rheumatoid arthritis Ann Intern Med 1999 131: 507–509

    Article  CAS  PubMed  Google Scholar 

  18. Joske DJ, Ma DT, Langlands DR, Owen ET . Autologous bone-marrow transplantation for rheumatoid arthritis Lancet 1997 350: 337—338

    Article  Google Scholar 

  19. Wulffraat N, van Royen A, Bierings M et al. Autologous haematopoietic stem-cell transplantation in four patients with refractory juvenile chronic arthritis Lancet 1999 353: 550–553

    Article  CAS  Google Scholar 

  20. Martini A, Maccario R, Ravelli A et al. Marked and sustained improvement two years after autologous stem cell transplantation in a girl with systemic sclerosis Arthr Rheum 1999 42: 807–811

    Article  CAS  Google Scholar 

  21. Tyndall A, Black C, Finke J et al. Treatment of systemic sclerosis with autologous haematopoietic stem cell transplantation Lancet 1997 349: 254

    Article  CAS  Google Scholar 

  22. Rosen O, Theil A, Massenkeil G et al. Autologous stem cell transplantation in refractory autoimmune diseases after ex vivo depletion of mononuclear cells Arthritis Res 2000 2: 327–336

    Article  CAS  PubMed  Google Scholar 

  23. Burt RK, Traynor A, Ramsey-Goldman R . Hematopoietic stem-cell transplantation for systemic lupus erythematosus New Engl J Med 1997 337: 1777–1778

    Article  CAS  Google Scholar 

  24. Fouillard L, Gorin NC, Laporte JP et al. Control of severe systemic lupus erythematosus after high-dose immunosuppressive therapy and transplantation of CD34+ purified autologous stem cells from peripheral blood Lupus 1999 8: 320–323

    Article  CAS  Google Scholar 

  25. Musso M, Porretto F, Crescimanno A et al. Autologous peripheral blood stem and progenitor (CD34+) cell transplantation for systemic lupus erythematosus complicated by Evans syndrome Lupus 1998 7: 492–494

    Article  CAS  Google Scholar 

  26. Marmont AM, van Lint MT, Gualandi F, Bacigalupo A . Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration Lupus 1997 6: 545–548

    Article  CAS  Google Scholar 

  27. Traynor A, Schroeder J, Rosa R et al. Treatment of severe lupus erythematosus with high-dose intense chemotherapy and hematopoietic stem cell transplantation: a phase I study Lancet 2000 356: 701–707

    Article  CAS  Google Scholar 

  28. Kurtzke JF . Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS) Neurology 1983 33: 1444–1452

    Article  CAS  PubMed  Google Scholar 

  29. Clements PJ, Lachenbruch PA, Seibold JR et al. Skin thickness score in systemic sclerosis: an assessment interobserver variability in 3 independent studies J Rheumatol 1993 20: 1892–1896

    CAS  Google Scholar 

  30. Bombardier C, Gladman DD, Urowitz MB et al. Derivation of the SLEDAI: a disease activity index for lupus patients Arthr Rheum 1992 35: 630–640

    Article  CAS  Google Scholar 

  31. Cleaver SA, Goldman JM . Use of G-CSF to mobilise PBSC in normal healthy donors – an international survey Bone Marrow Transplant 1998 21: (Suppl. 3) S29–31

    Article  Google Scholar 

  32. Openshaw H, Stuve O, Antel JP et al. Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor Neurology 2000 54: 2147–2150

    Article  CAS  Google Scholar 

  33. Snowden JA, Biggs JC, Milliken ST et al. A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis Bone Marrow Transplant 1998 22: 1035–1041

    Article  CAS  Google Scholar 

  34. Locatelli F, Perotti C, Torretta L et al. Mobilization and selection of peripheral blood hematopoietic progenitors in children with systemic sclerosis Haematologica 1999 84: 839–843

    CAS  Google Scholar 

  35. McGonagle D, Rawstron A, Richards S et al. A phase 1 study to address the safety and efficacy of granulocyte colony-stimulating factor for the mobilization of hematopoietic progenitor cells in active rheumatoid arthritis Arthr Rheum 1997 40: 1838–1842

    Article  CAS  Google Scholar 

  36. Arpinati M, Green CL, Heimfeld S et al. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells Blood 2000 95: 2484–2490

    CAS  Google Scholar 

  37. Reddy V, Hill GR, Pan L et al. G-CSF modulates cytokine profile of dendritic cells and decreases acute graft-versus-host disease through effects on the donor rather than the recipient Transplantation 2000 69: 691–693

    Article  CAS  Google Scholar 

  38. Reyes E, Garcia-Castro I, Esquivel F et al. Granulocytecolony-stimulating factor (G-CSF) transiently suppresses mitogen-stimulated T-cell proliferative response Br J Cancer 1999 80: 229–235

    Article  CAS  PubMed  Google Scholar 

  39. Rondelli D, Raspadori D, Anasetti C et al. Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF-mobilized peripheral blood cells Bone Marrow Transplant 1998 22: 631–637

    Article  CAS  Google Scholar 

  40. Hartung T . Immunomodulation by colony-stimulating factors Rev Physiol Biochem Pharmacol 1999 136: 1–164

    Article  CAS  Google Scholar 

  41. Hartung T, Doecke WD, Bundschuh D et al. Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions Clin Pharmacol Ther 1999 66: 415–424

    Article  CAS  Google Scholar 

  42. Bellucci R, De Propris MS, Buccisano F et al. Modulation of VLA-4 and L-selectin expression on normal CD34+ cells during mobilization with G-CSF Bone Marrow Transplant 1999 23: 1–8

    Article  CAS  Google Scholar 

  43. Martino R, Sureda A, Brunet S . Peripheral blood stem cell mobilization in refractory autoimmune Evans syndrome: a cautionary case report Bone Marrow Transplant 1997 20: 521

    Article  CAS  Google Scholar 

  44. Singhal S, Mehta J, Desikan K et al. Collection of peripheral blood stem cells after a preceding autograft: unfavorable effect of prior interferon-alpha therapy Bone Marrow Transplant 1999 24: 13–27

    Article  CAS  Google Scholar 

  45. Klingemann HG, Eaves CJ, Barnett MJ et al. Transplantation of patients with high risk acute myeloid leukemia in first remission with autologous marrow cultured in interleukin-2 followed by interleukin-2 administration Bone Marrow Transplant 1994 14: 389–396

    CAS  Google Scholar 

  46. Feng CS, Ng MH, Szeto RS, Li EK . Bone marrow findings in lupus patients with pancytopenia Pathology 1991 23: 5–7

    Article  CAS  Google Scholar 

  47. Otsuka T, Nagasawa K, Harada M, Niho Y . Bone marrow microenvironment of patients with systemic lupus erythematosus J Rheumatol 1993 20: 967–971

    CAS  Google Scholar 

  48. Koch AE, Kronfeld-Harrington LB, Szekanecz Z et al. In situ expression of cytokines and cellular adhesion molecules in the skin of patients with systemic sclerosis. Their role in early and late disease Pathobiology 1993 61: 239–246

    Article  CAS  Google Scholar 

  49. Hasegawa M, Sato S, Takehara K . Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta) in patients with systemic sclerosis: MCP-1 and MIP-1alpha may be involved in the development of pulmonary fibrosis Clin Exp Immunol 1999 117: 159–165

    Article  CAS  PubMed  Google Scholar 

  50. Veale DJ, Kirk G, McLaren M, Belch JJ . Clinical implications of soluble intercellular adhesion molecule-1 levels in systemic sclerosis Br J Rheumatol 1998 3: 1227–1228

    Article  Google Scholar 

  51. Papayannopoulou T . Hematopoietic stem/progenitor cell mobilization. A continuing quest for etiologic mechanisms Ann NY Acad Sci 1999 872: 187–197

    Article  CAS  Google Scholar 

  52. Broxmeyer HE, Kim CH, Cooper SH et al. Effects of CC, CXC, C, and CX3C chemokines on proliferation of myeloid progenitor cells, and insights into SDF-1-induced chemotaxis of progenitors Ann NY Acad Sci 1999 872: 142–162

    Article  CAS  Google Scholar 

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Acknowledgements

Dr Snowden and Dr Moore would like to thank Amgen Australia, Melbourne, for permission to use their data in this analysis.

Author information

Authors and Affiliations

  1. Department of Medicine, Northwestern University Medical Center, Chicago, IL, USA

    RK Burt

  2. Department of Hematology, George Papanicolaou General Hospital, Thessaloniki, Greece

    A Fassas

  3. University Hospital of Leicester, Leicester, UK

    JA Snowden

  4. St Vincent's Hospital, Sydney, Australia

    JA Snowden

  5. Leiden University Medical Center, Leiden, The Netherlands

    JM van Laar

  6. University Hospital Kralovske Vinohrady, Prague, Czech Republic

    T Kozak

  7. Universitair Medisch Centrum, Utrecht, The Netherlands

    NM Wulffraat

  8. Fred Hutchinson Research Cancer Center, Seattle, WA, USA

    RA Nash

  9. National Institutes of Health, National Heart Lung and Blood Institute, Hematology Branch, Bethesda, MD, USA

    CE Dunbar

  10. Universitatsklinikum Campus Charite Mitte, Berlin, Germany

    R Arnold

  11. Royal Free and University Medical School, London, UK

    G Prentice

  12. Leeds General Infirmary, Leeds, UK

    S Bingham

  13. Centro Trapianti di Midollo Osseo, Ospedale San Martino, Genoa, Italy

    AM Marmont

  14. University of Colorado, Denver, CO, USA

    PA McSweeney

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Appendix

Appendix

The following investigators also contributed to this study: John Moore, St Vincents Hospital, Sydney, Australia; Christoph Fiehn and Manfred Hensel, University of Heidelberg, Department of Internal Medicine, Heidelberg, Germany; William H Burns, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Steven Pavletic, University of Nebraska, Omaha, Nebraska, USA; Riccardo Saccardi, Azienda Ospedaliera Careggi, Firenze, Italy; Ouyang Jian and Su Chang, Gu Lou Hospital, Nanjing University Medical School, Nanjing, Peoples Republic of China; Mary Territo, University of California at Los Angeles, Los Angeles, California, USA; Ewa Carrier, University of California, San Diego, California, USA; Francesca Gualandi, Ospedale San Martino, Genoa; Federico Papineschi, S Chiara's Hospital, Pisa, Italy; Giorgio La Nasa, Binaghi Hospital, Cagliari, Italy; Robrecht De Bock, Algemeen Ziekenhuis Middelheim, Antwerpen, Belgium; Friedrich Scheuning, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Paolo Di Bartolomeo, Bone Marrow Transplantation Unit, Ospedale Civile, Pescara, Italy; Willem E Fibbe, Leiden University Medical Center, Leiden, The Netherlands; Richard D Huhn, Coriell Institute for Medical Research, Camden, New Jersey, USA; Andres Theil and Oliver Rosen, Universitatsklinikum Campus Charite Mitte, Berlin, Germany; Ann Traynor, Kehuan Luo, Borko Jovanovicv and Yu Oyama, Northwestern University Medical Center, Department of Medicine, Chicago, Illinois, USA; Laura Herbert, Royal Free and University Medical School, London, UK; Susan Leitman, National Institutes of Health, Warren Grant Magnuson Clinical Center, Bethesda, Maryland, USA; Keith Sullivan, Duke University Medical Center, Durham, North Carolina, USA; Ineke Slaper, Universitair Medisch Centrum, Utrecht, The Netherlands.

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Burt, R., Fassas, A., Snowden, J. et al. Collection of hematopoietic stem cells from patients with autoimmune diseases. Bone Marrow Transplant 28, 1–12 (2001). https://doi.org/10.1038/sj.bmt.1703081

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