Mitoxantrone immunotherapy in multiple sclerosis.

Abstract

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 that multiple sclerosis is a chronic disease, and that the benefit is limited to the period of administration of any treatment.