link.springer.com

Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China - Neurological Sciences

  • ️Zhang, Xueguang
  • ️Thu Dec 08 2011

Abstract

Autologous haematopoietic stem cell transplantation (AHSCT) is a promising treatment for multiple sclerosis (MS) patients who have not adequately responded to conventional therapies. We retrospectively evaluated the safety and long-term clinical outcome of AHSCT in MS patients in China. Twenty-five patients with various types of MS were treated with AHSCT. Peripheral blood stem cells were derived by leukapheresis after mobilized with granulocyte colony-stimulating factor. Then CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion, with the conditioning regimen BEAM adopted and early and late toxicities recorded. Long-term responses were evaluated by the expanded disability status scale (EDSS), progression-free survival and gadolinium-enhanced magnetic resonance imaging scans. 10, 7 and 8 patients experienced neurological improvement, stabilization and progression, respectively. The median EDSS scores observed over 1-year follow-up after transplantation (5.5–7.0) were consistently lower than the baseline (8.0). The progression-free survival rate was 74, 65 and 48% at 3, 6 and 9 years post-transplant. 58% cases (7/12) had active lesions at baseline and all turned to inactive status in the years of follow-up. 25% cases (3/12) experienced progression after transplantation but had no active lesions in MRI over the whole follow-up period. 17% cases (2/12) without active lesions at baseline progressed active lesions in MRI. The major early toxicity resulted in fever and late toxicity caused transplantation-related mortality due to severe pneumonia and varicella-zoster virus hepatitis, respectively. AHSCT is a feasible treatment for severe MS and its long-term efficacy is favorable.

Access this article

Log in via an institution

Subscribe and save

  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cheng Q, Miao L, Zhang J et al (2007) A population-based survey of multiple sclerosis in Shanghai. China Neurol 68:1495–1500

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Muraro PA, Abrahamsson SV (2010) Resetting autoimmunity in the nervous system: the role of hematopoietic stem cell transplantation. Curr Opin Investig Drugs 11:1265–1275

    PubMed  CAS  Google Scholar 

  4. Van Wijmeersch B, Sprangers B, Dubois B et al (2008) Autologous and allogeneic hematopoietic stem cell transplantation for multiple sclerosis: perspective on mechanisms of action. J Neuroimmunol 197:89–98

    Article  PubMed  Google Scholar 

  5. Mezey E, Key S, Vogelsang G et al (2003) Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci 100:1364–1369

    Article  PubMed  CAS  Google Scholar 

  6. Brazelton TR, Rossi FM, Keshet GI et al (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290:1775–1779

    Article  PubMed  CAS  Google Scholar 

  7. Mancardi G, Saccardi R (2008) Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol 7:626–636

    Article  PubMed  Google Scholar 

  8. Ni XS, Ouyang J, Zhu WH et al (2006) Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three yr of follow up in 21 patients. Clin Transplant 20:485–489

    Article  PubMed  Google Scholar 

  9. van Bekkum DW (2004) Autologous stem cell transplantation in animal models of autoimmune diseases. In: Burt RK, Marmont AM (eds) Stem cell therapy for immune diseases. Landes Biosciences, Georgetown, pp 237–244

    Google Scholar 

  10. Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517

    Article  PubMed  CAS  Google Scholar 

  11. Saiz A, Saccardi R, Mancardi GL et al (2008) Autologous HSCT for severe progressive multiple sclerosis in the Italian prospective, multicentre GITMO-Neuro trial: long term follow-up. Bone Marrow Transplant 41:S17

    Google Scholar 

  12. Saiz A, Blanco Y, Berenguer J et al (2008) Clinical outcome 6 years after autologous hematopoietic stem cell transplantation in multiple sclerosis. Neurologia 23:405–407

    PubMed  CAS  Google Scholar 

  13. Saccardi R, Kozak T, Bocelli-Tyndall C et al (2006) Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for blood and marrow transplantation autoimmune diseases working party database. Mult Scler 12:814–823

    Article  PubMed  CAS  Google Scholar 

  14. Comi G, Kappos L, Clanet M et al (2000) Guideline for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for blood and marrow transplantation and the European Charcot Foundation. J Neurol 247:376–382

    Article  PubMed  CAS  Google Scholar 

  15. Burt RK, Loh Y, Cohen B et al (2009) Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol 8:244–253

    Article  PubMed  CAS  Google Scholar 

  16. Fagius J, Lundgren J, Oberg G (2009) Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler 15:229–237

    Article  PubMed  CAS  Google Scholar 

  17. Matthews WB (1991) Clinical aspects. Course and prognosis. In: Matthews WB (ed) McAlpine’s multiple sclerosis, second edition edn. Churchill Livingstone, Edinburgh, pp 139–163

    Google Scholar 

  18. Mancardi GL, Murialdo A, Rossi P et al (2005) Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult Scler 11:367–371

    Article  PubMed  Google Scholar 

  19. Havrdova E (2005) Aggressive multiple sclerosis—is there a role for stem cell transplantation? J Neurol 252:III34–III37

    Article  PubMed  Google Scholar 

  20. Kimiskidis V, Sakellari I, Tsimourtou V et al (2008) Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome. Mult Scler 14:278–283

    Article  PubMed  CAS  Google Scholar 

  21. Burt RK, Cohen B, Rose J et al (2005) Hematopoietic stem cell transplantation for multiple sclerosis. Arch Neurol 62:860–864

    Article  PubMed  Google Scholar 

  22. ASTIMS “Autologous Stemcell Transplantation International Multiple Sclerosis trial”. http://www.astims.org

  23. Krasulová E, Trneny M, Kozák T et al (2010) High-dose immunoablation with autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a single centre 10-year experience. Mult Scler 16:685–693

    Article  PubMed  Google Scholar 

  24. Mancardi GL, Saccardi R, Filippi M et al (2001) Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Neurology 57:62–68

    Article  PubMed  CAS  Google Scholar 

  25. Saiz A, Blanco Y, Carreras E et al (2004) Clinical and MRI outcome after autologous hemtopoietic stem cell transplantation in MS. Neurology 62:282–284

    Article  PubMed  CAS  Google Scholar 

  26. Fassas A, Kimiskidis VK, Sakellari I et al (2011) Long-term results of stem cell transplantation for MS: a single-center experience. Neurology 76:1066–1070

    Article  PubMed  CAS  Google Scholar 

  27. Zivadinov R, Bakshi R (2004) Central nervous system atrophy and clinical status in multiple sclerosis. J Neuroimaging 14:27–35

    Article  Google Scholar 

Download references

Acknowledgment

This work was supported by the Project of Jiangsu Province’s Laboratory of Clinical Immunology (NO.2003-19).

Author information

Authors and Affiliations

  1. Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People’s Republic of China

    Bing Chen, Min Zhou, Jian Ouyang, Rongfu Zhou, Jingyan Xu, Qiguo Zhang, Yonggong Yang, Yong Xu, Xiaoyan Shao, Li Meng, Jing Wang & Xueguang Zhang

  2. Center of Bone Marrow Transplantation, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China

    Bing Chen, Min Zhou, Jian Ouyang, Rongfu Zhou, Jingyan Xu, Qiguo Zhang, Yonggong Yang, Yong Xu, Xiaoyan Shao, Li Meng, Jing Wang & Xueguang Zhang

  3. Department of Neurology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China

    Yun Xu & Xiushi Ni

Authors

  1. Bing Chen

    You can also search for this author inPubMed Google Scholar

  2. Min Zhou

    You can also search for this author inPubMed Google Scholar

  3. Jian Ouyang

    You can also search for this author inPubMed Google Scholar

  4. Rongfu Zhou

    You can also search for this author inPubMed Google Scholar

  5. Jingyan Xu

    You can also search for this author inPubMed Google Scholar

  6. Qiguo Zhang

    You can also search for this author inPubMed Google Scholar

  7. Yonggong Yang

    You can also search for this author inPubMed Google Scholar

  8. Yong Xu

    You can also search for this author inPubMed Google Scholar

  9. Xiaoyan Shao

    You can also search for this author inPubMed Google Scholar

  10. Li Meng

    You can also search for this author inPubMed Google Scholar

  11. Jing Wang

    You can also search for this author inPubMed Google Scholar

  12. Yun Xu

    You can also search for this author inPubMed Google Scholar

  13. Xiushi Ni

    You can also search for this author inPubMed Google Scholar

  14. Xueguang Zhang

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Jian Ouyang.

Additional information

M. Zhou and B. Chen contribute equally to this article and should be considered as co-first authors.

About this article

Cite this article

Chen, B., Zhou, M., Ouyang, J. et al. Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China. Neurol Sci 33, 881–886 (2012). https://doi.org/10.1007/s10072-011-0859-y

Download citation

  • Received: 17 March 2011

  • Accepted: 11 November 2011

  • Published: 08 December 2011

  • Issue Date: August 2012

  • DOI: https://doi.org/10.1007/s10072-011-0859-y

Keywords