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Multiple Sclerosis

High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis

Abstract

High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS. We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy with either in vitro or in vivo T cell depletion. Median EDSS and SNRS scores at the time of inclusion were 6.5 (6.5–7.5) and 56 (44–65), respectively. PBPC mobilisation was safe with no serious adverse effects, and without significant aggravation of disability. One patient improved significantly (by 1.0 point on EDSS) after the mobilisation. Two mobilisation failures were observed. No life-threatening events occurred during the transplantation. All grafted patients, except one, at least stabilised their disability status. One patient improved significantly (by 1.5 points on EDSS), two patients improved slightly (by 0.5 points on EDSS), one patient worsened by 1.0 point on the EDSS in 10 months. Improvement occurred with a delay of 2–4 months. Median EDSS and SNRS of grafted patients at the last follow up were 6.5 (5.5–8.5) and 64 (39–73), respectively with median follow-up of 8.5 months. Further follow-up is needed to determine the disease course after complete immune reconstitution. Bone Marrow Transplantation (2000) 25, 525–531.

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References

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

    CAS  PubMed  Google Scholar 

  2. Marmont AM . Stem cell transplantation for severe autoimmune disorders, with special reference to rheumatic diseases J Rheumatol 1997 24: (Suppl. 48) 13–18

    Google Scholar 

  3. Slavin S . Treatment of life threatening autoimmune diseases with myeloablative doses of immunosuppressive agents: experimental background and rationale for ABMT BoneMarrow Transplant 1993 12: 85–88

    CAS  Google Scholar 

  4. Snowden JA, Brooks PM, Boggs JC . Haematopoietic stem cell transplantation for autoimmune diseases Br J Haematol 1997 99: 9–23

    Article  CAS  Google Scholar 

  5. Tyndall A, Grathwohl A . Blood and marrow stem cell transplants in autoimmune disease: a consensus report written on behalf of the EULAR and EBMT Bone Marrow Transplant 1997 19: 643–645

    Article  CAS  Google Scholar 

  6. Hallpike, JF . Clinical aspects of multiple sclerosis. In: Hallpike JF, Adams CWM, Tourtellotte WW (eds) Multiple Sclerosis Chapman and Hall: London 1983 pp 129–161

    Google Scholar 

  7. Hartung HP . Pathogenesis of multiple sclerosis. In: Abramsky O, Ovadia H (eds) Frontiers in Multiple Sclerosis Martin Dunitz: London 1997 pp 45–60

    Google Scholar 

  8. Weiner HL, Mackin GA, Orav EJ et al. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group Neurology 1993 43: 810–918

    Google Scholar 

  9. Edan G, Miller D, Clanet M et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis J Neurol Neurosurg Psych 1997 62: 112–118

    Article  CAS  Google Scholar 

  10. Kozak T, Gregora E, Havrdova E et al. High dose immunoablative chemotherapy with double T cell depletion in the treatment of multiple sclerosis Bone Marrow Transplant 1999 23: (Suppl. 1) S35 (Abstr. 108)

    Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Sipe JC, Knobler RL, Brahney SL et al. A neurologic rating scale (NRS) for use in multiple sclerosis Neurology 1984 34: 1368–1372

    Article  CAS  Google Scholar 

  13. Brodsky AR, Petri M, Smith BD et al. Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease Ann Intern Med 1998 129: 1031–1035

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Knaan-Shanzer S, Houben P, Bohre EPM et al. Remission induction of adjuvant arthritis in rats by total body irradiation and autologous bone marrow transplantation Bone Marrow Transplant 1991 8: 333–338

    CAS  PubMed  Google Scholar 

  16. Karussis DM, Vourka-Karussis U, Lehmann D et al. Prevention and reversal of adoptively transferred, chronic relapsing experimental autoimmune encephalomyelitis with a single high dose cytoreductive treatment followed by syngeneic bone marrow transplantation J Clin Invest 1993 92: 765–772

    Article  CAS  Google Scholar 

  17. van Gelder M, Kinwel-Bohré EPM, van Bekkum DW . Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT Bone Marrow Transplant 1993 11: 233–241

    CAS  PubMed  Google Scholar 

  18. McAllister LD, Beatty PG, Rose J . Allogeneic BMT for chronic myelogenous leukemia in a patient with multiple sclerosis. Case report Bone Marrow Transplant 1997 19: 395–397

    Article  CAS  Google Scholar 

  19. Liu Yin JA, Jowitt SN . Resolution of immune-mediated diseases following allogeneic BMT for leukemia Bone Marrow Transplant 1992 9: 31–33

    Google Scholar 

  20. Hentschke P, Fredrikson S, Lonqvist B et al. Allogeneic stem cell transplantation for CML in two patients with MS Bone Marrow Transplant 1999 23: (Suppl. 1) S34 (Abstr. 106)

    Google Scholar 

  21. Meloni G, Capria S, Vignetti M, Mandelli F . Blast crisis of CML in long-lasting systemic lupus erythematosus: regression of both diseases after autologous BMT Blood 1997 89: 4659–4666

    CAS  PubMed  Google Scholar 

  22. Snowden JA, Patton WN, O'Donnell JL et al. Prolonged remission of longstanding lupus erythematosus after autologous BMT for non-Hodgkin's lymphoma Bone Marrow Transplant 1997 19: 1247–1250

    Article  CAS  Google Scholar 

  23. Salzman D, Tami J, Jackson C et al. Clinical remission of myasthenia gravis in patient after high-dose chemotherapy and autologous transplantation with CD34+ stem cells Blood 1994 84: (Suppl. 1) 808 (Abstr. 206a)

    Google Scholar 

  24. Cooley HM, Snowden JA, Grigg A, Wicks IP . Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy Arthritis Rheum 1997 40: 1712–1715

    Article  CAS  Google Scholar 

  25. van Bekkum DW . New opportunities for the treatment of severe autoimmune diseases: bone marrow transplantation Clin Immunol Immunopathol 1998 89: 1–10

    Article  CAS  Google Scholar 

  26. van Bekkum DW . BMT in experimental autoimmune diseases Bone Marrow Transplant 1993 11: 183–187

    CAS  PubMed  Google Scholar 

  27. Marmont AM, van Bekkum DW . Stem cell transplantation for severe autoimmune diseases: new proposals but still unanswered questions Bone Marrow Transplant 1995 16: 497–498

    CAS  PubMed  Google Scholar 

  28. Storek J, Witherspoon RP, Storb R . T cell reconstitution after bone marrow transplantation into adult patients does not resemble T cell development in early life Bone Marrow Transplant 1995 16: 413–425

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  30. 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: 3505–3515

    CAS  PubMed  Google Scholar 

  31. van Bekkum DW . Autologous stem cell therapy for treatment of autoimmune diseases Exp Hematol 1998 26: 831–834

    CAS  PubMed  Google Scholar 

  32. Euler HH, Marmont AM, Bacigalupo A . Early recurrence or persistence of autoimmune disease after unmanipulated autologous stem cell transplantation Blood 1996 88: 3621–3625

    CAS  PubMed  Google Scholar 

  33. Marmont AM, van Lint MT, Occhini D et al. Failure of autologous stem cell transplantation in refractory thrombocytopenic purpura Bone Marrow Transplant 1998 22: 827–828

    Article  CAS  Google Scholar 

  34. Skoda RC, Tichelli A, Tyndall A et al. Autologous peripheral blood stem cell transplantation in a patient with chronic autoimmune thrombocytopenia Br J Haematol 1997 99: 56–57

    Article  CAS  Google Scholar 

  35. Koehne G, Zeller W, Stockschlaeder M, Zander AR . Phenotype of lymphocyte subsets after autologous peripheral blood stem cell transplantation Bone Marrow Transplant 1997 19: 149–156

    Article  CAS  Google Scholar 

  36. Guillaume T, Rubinstein D, Symann M . Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation Blood 1998 92: 1471–1490

    CAS  PubMed  Google Scholar 

  37. Slavin S, Nagler A, Kapelushnik Y et al. Nonmyeloablative stem cell transplantation with lethal cytoreduction for the treatment of malignant and non-malignant hematologic diseases Blood 1998 91: 756–763

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Dr L Rosa, the head of the Department of Clinical Haematology, University Hospital Královské Vinohrady, the nursing staff of the BMT unit, especially M Patorkova, and the staff of the Apheresis Unit at the Blood Transfusion Department, especially Dr M Greplova, Dr D Kraftova, and Dr J Kracikova for their substantial support.

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Kozák, T., Havrdová, E., Pit'ha, J. et al. High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis. Bone Marrow Transplant 25, 525–531 (2000). https://doi.org/10.1038/sj.bmt.1702180

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