Mitoxantrone, a cytotoxic agent recently developed, was subsequently found a very potent immunosuppressor. Experimental data in experimental allergic encephaloymyelitis demonstrated a dramatic suppression of both active and passive forms. Immune effects concern cellular and humoral components and are particularly persistent B cell subset is preferentially deleted. Suppressor cells are relatively spared and suppression becomes dominant In cancer therapy, the main advantages of mitoxantrone are a definitely better immediate tolerance and very low delayed adverse reactions (carcinogenicity, teratogenicity, impact on reproductive organs). Given its major immunosuppressive activity and its better tolerance, mitoxantrone was a potential candidate for multiple sclerosis therapy. Several clinical trials have confirmed the remarkable efficacy of mitoxantrone to reduce both attack and progression rates. Unfortunately the cardiotoxicity was found more frequent than expected and limits the maximum cumulative dose to 120 mg/m2. Mitoxantrone, when employed properly, may be useful in patients with frequent and disabling excerbations and/or rapidly progressing disability. It must be kept in mind mat multiple sclerosis is a chronic disease, and that the benefit is limited to the period of administration of any treatment.
1 Baker D, O'Neill JK, Davison AN, Turk JL. (1992) Control of immune-mediated disease of the central nervous system requires the use of a neuroactive agent: elucidation by the action of mitoxantrone. Clin Exp Immunol90: 124–128.
2.
2 Bastianello S et al. (1994) A controlled trial of mitoxantrone in multiple sclerosis: serial MRI evaluation at 1 year. Can J Neurol Sci21: 266–270.
3.
3 Bisteau M, Devos G, Brucher JM, Gonsette RE. (1989) Prevention of subacute experimental allergic encephalomyelitis in Guinea-pigs with desferrioxamine, isoprinosine and mitoxantrone. In: Gonsette RE, Delmotte P, ed. Recent advances in multiple sclerosis therapy.Elsevier Science Publishers, International Congress Series 863: pp 299–300.
4.
4 Cook SD et al. (1995) Combination total lymphoid irradiation and low-dose corticosteroid therapy for progressive multiple sclerosis. Acta Neurol Scand91: 22–27.
5.
5 De Castro S et al. (1995) Noninvasive assessment of mitoxantrone cardiotoxicity in relapsing remitting multiple sclerosis. J Clin Pharmacol35: 627–632.
6.
6 Faulds D, Balfour JA, Chrisp P, Langtry HD. (1991) Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs41: 400–449.
7.
7 Fetzer U, Laufen H, Mauch E, Kornhuber HH. (1981) Changes in subsets and surface marker distribution of lymphocytes in MS patients during immunotherapy. In: Weithölter H et al., ed. Current concepts in multiple sclerosis.Elsevier Science Publishers, International Congress Series 960: pp 281–284.
8.
8 Fidler JM, Quinn DeJoy S, Gibbons JJ Jr. (1986) Selective immunomodulation by the antineoplastic agent mitoxantrone. I. Suppression of B Lymphocyte function. J Immunol137: 727–732.
9.
9 Fidler JM, Quinn DeJoy S, Smith FR, Gibbons JJ Jr. (1986) Selective immunomodulation by the antineoplastic agent mitoxantrone. II. Nonspecific adherent suppressor cells derived from mitoxantrone-treated mice. J Immunol136: 2747–2754.
10.
10 Fieschi C et al. (1993) MRI in monitoring the treatment of relapsing-remitting multiple sclerosis with mitoxantrone. Multiple Sclerosis Satellite Symposium, International Federation of Multiple Sclerosis Societies, September 10–13, Victoria Canada (Abstract 2–08).
11.
11 French and British Multiple Sclerosis Mitoxantrone Trial Group, Edan G. (1995) Demonstration of the efficacy of mitoxantrone (MTX) using MRI in MS patients with a very active disease.J Neuroimmunol (suppl 1): 16: (Abstract).
12.
12 Gonsette RE, Demonty L, Delmotte P. (1977) Intensive immunosuppression with cyclophosphamide in multiple sclerosis. Follow-up of 100 patients for 2–6 years. J Neurol214: 173–181.
13.
13 Gonsette RE, Demonty L. (1989) Mitoxantrone: a new immunosuppressive agent in multiple sclerosis. In: Gonsette RE, Delmotte P, ed. Recent advances in multiple sclerosis therapy.Elsevier Science Publishers, International Congress Series 863: pp 161–164.
14.
14 Gonsette RE, Demonty L. (1990) Immunosuppression with mitoxantrone in multiple sclerosis: A pilot study for 2 years in 22 patients.Neurology40 (suppl 1): 261 (Abstract).
15.
15 Gonsette RE, Demonty LJ, Lissoir FA, Defalque AS. (1993) Long term tolerance of mitoxantrone in multiple sclerosis.Multiple Sclerosis Satellite Symposium, International Federation of Multiple Sclerosis Societies, September 10–13, Victoria Canada (Abstract 2–10).
16.
16 Kappos L et al. (1990) Mitoxantrone (Mx) in the treatment of rapidly progressive MS: A pilot study with serial gadolinium (Gd)-enhanced MRI.Neurology40 (suppl 1): 261 (Abstract).
17.
17 Levine S, Saltzman A. (1986) Regional suppression, therapy after onset and prevention of relapses in experimental allergic encephalomyelitis by mitoxantrone. J Neuroimmunol13: 175–181.
18.
18 Lublin FD, Lavasa M, Viti C, Knobler RL. (1987) Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone. Clin Immunol Immunopathol45: 122–128.
19.
19 Mauch E et al. (1992) Treatment of multiple sclerosis with mitoxantrone. Eur Arch Psychiatry Clin Neurosci242: 96–102.
20.
20 Noseworthy JH et al. (1991) A phase II evaluation of mitoxantrone HCl in the treatment of progressive multiple sclerosis.Neurology41 (suppl 1): 146 (Abstract).
21.
21 Noseworthy JH et al. (1993) An open-trial evaluation of mitoxantrone in the treatment of progressive MS. Neurology43: 1401–1406.
22.
22 Ridge SC et al. (1985) Suppression of experimental allergic encephalomyelitis by mitoxantrone. Clin Immunol Immunopathol35: 35–42.
23.
23 Schneider T et al. (1985) Mitoxantrone: an immunosuppressive agent potentially useful in the organ transplantation. Fedn Proc Fedn Am Socs Exp Biol44: 1681 (Abstract).
24.
24 Shenkenberg TD, Von Hoff DD. (1986) Possible mitoxantrone-induced amenorrhea. Cancer Treat Rep70: 659–661.
25.
25 Stewart DJ et al. (1986) Human autopsy tissue concentrations of mitoxantrone. Cancer Treat Rep70: 1255–1261.
26.
26 Wang BS et al. (1987) Induction of alloreactive immunosuppression by 1, 4-bis [(2-aminoethyl)amino]-5, 8-dihydroxy-9, 10-anthracenedione dihydrochloride (CL 232, 468). Int J Immunopharmac6: 475–482.
27.
27 Wang BS et al. (1987) Relationship of chemical structures of anthraquinones with their effects on the suppression of immune responses. Int J Immunopharmac9: 733–739.
28.
28 Watson CM et al. (1991) Suppression of demyelination by mitoxantrone. Int J Immunopharmac13: 923–930.
29.
29 Weiner HL et al. (1993) Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: Final report of the northeast cooperative multiple sclerosis treatment group. Neurology43: 910–918.
30.
30 Zaffaroni M, Ghezzi A, Baldini SM, Zibetti A. (1995) Effetti immunosuppressori del mitoxantrone nella sclerosi multipla cronica-progressiva. In: Ghezzi A et al., ed. La ricerca sulla sclerosi multipla in ItaliaMomento Medico Publisher, pp 112–114.
