Malignant multiple sclerosis (MS) is a rare but clinically important subtype of MS characterized by the rapid development of significant disability in the early stages of the disease process. These patients are refractory to conventional immunomodulatory agents and the mainstay of their treatment is plasmapheresis or immunosuppression with mitoxantrone, cyclophosphamide, cladribine or, lately, bone marrow transplantation. We report on the case of a 17-year old patient with malignant MS who was treated with high-dose chemotherapy plus anti-thymocyte globulin followed by autologous stem cell transplantation. This intervention resulted in an impressive and long-lasting clinical and radiological response. It is concluded that intensive immunosuppression followed by autologous stem cell transplantation is a viable therapeutic option in patients with malignant MS unresponsive to conventional forms of treatment. Multiple Sclerosis 2008; 17 : 278—283. http://msj.sagepub.com
Noseworthy JH , Hartung HPMultiple sclerosis and related conditions . In: Noseworthy JH, ed. Neurological therapeutics. Principles and practice, second edition. Informa Healthcare2006: Vol I: 1224—50.
2.
Weinshenker BGTherapeutic plasma exchange for acute inflammatory demyelinating syndromes of the central nervous system. J Clin Apher1999; 14: 144—8.
3.
Weinshenker BGPlasma exchange for severe attacks of inflammatory demyelinating diseases of the central nervous system. J Clin Apher2001; 16: 39—42.
4.
Edan G.Sclerose en plaques agressive. Definition et indication therapeutique particuliere . Presse Med2004; 33: 187—91.
5.
Jeffery DR, Lefkowitz DS, Crittenden JPTreatment of Marburg variant multiple sclerosis with mitoxantrone. J Neuroimaging2004; 14: 58—62.
6.
Rice G.Cladribine and chronic progressive multiple sclerosis: the results of a multicenter trial. Neurology1997; 48: 1730.
7.
Weinstock-Guttman B., Kinkel RP, Cohen JA, Ransohoff RM, Schwetz K., Gogol D. et al. Treatment of fulminant multiple sclerosis with intravenous cyclophosphamide. Neurologist1997; 3: 178—85.
8.
Mancardi GL, Murialdo A., Rossi P., Gualandi F., Martino G., Marmont A. et al. Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult Scler2005 ; 11: 367—71.
9.
Havrdova E.Aggressive multiple sclerosis—is there a role for stem cell transplantation?J Neurol2005; 3(Suppl): III/34—III/37.
10.
McDonald WI , Compston A., Edan G., Goodkin D., Hartung HP, Lublin FD et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol2001; 50: 121—7.
11.
Koziol JA, Lucero A., Sipe JC, Romine JS, Beutler E.Responsiveness of the scripps neurologic rating scale during a multiple sclerosis clinical trial. Can J Neurol Sci1999; 26: 283—9.
12.
Fassas A., Anagnostopoulos A., Kazis A., Kapinas K., Sakellari I., Kimiskidis V. et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant1997; 20: 631—8.
13.
Karussis D. , Vourka-Karoussis U., Mizrachi-Koll R., Abramsky O.Acute/relapsing experimental autoimmune encephalomyelitis: induction of long lasting, antigen-specific tolerance by syngeneic bone marrow transplantation. Mult Scler1999; 5: 17— 21.
14.
Muraro PA, Douek DC, Packer A., Chung K., Guenaga FJ, Cassiani-Ingoni R. et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med2005; 201: 805—16.
15.
Atkins H., Freedman M.Immunoablative therapy as a treatment for aggressive multiple sclerosis. Neurol Clin2005; 23: 273—300.
16.
Farhey YD, Herman JHVasculitis complicating granulocyte colony stimulating factor treatment of leukopenia and infection in Felty's syndrome. J Rheumatol1995; 22: 1179—82.
17.
Euler HH, Harten P., Zeuner RA, Schwab UMRecombinant human granulocyte colony stimulating factor in patients with systemic lupus erythematosus associated neutropenia and refractory infections. J Rheumatol1997; 24: 2153—7.
18.
Openshaw H. , Stuve O., Antel JP, Nash R., Lund BT, Weiner LP et al. Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor. Neurology2000; 54: 2147—50.
19.
Openshaw H. , Lund BT, Kashyap A., Atkinson R., Sniecinski I., Weiner LP et al. Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring. Biol Blood Marrow Transplant2000; 6: 563—75.
20.
Burt RK, Fassas A., Snowden J., van Laar JM, Kozak T., Wulffraat NM et al. Collection of hematopoietic stem cells from patients with autoimmune diseases. Bone Marrow Transplant2001; 28: 1—12.
21.
Xu S., Hoglund M., Hakansson L., Venge P.Granulocyte colony-stimulating factor (G-CSF) induces the production of cytokines in vivo. Br J Haematol2000; 108: 848—53.
22.
Keegan M., König F., McClelland R., Brück W., Morales Y., Bitsch A. et al. Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet2005; 366: 579—82.
23.
Lucchinetti CF, Bruck W., Parisi J., Scheithauer B., Rodriguez M., Lassmann H.Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol2000; 47: 707—17.
24.
Saccardi R. , Kozak T., Bocelli-Tyndall C., Fassas A., Kazis A., Havrdova E. et al. Autoimmune diseases working party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European group for blood and marrow transplantation autoimmune diseases working party database. Mult Scler2006; 12: 814—23.
