The pathogenesis of myasthenia gravis (MG) involves an antibody-mediated autoimmune attack directed against acetylcholine receptors (AchRs) at the level of neuromuscular junctions. Conventional treatment of MG with immunosuppressive agents (such as corticosteroids, aziathioprine, cyclosporin-A, and the like) is often effective. Myasthenia gravis patients who do not respond to conventional immunotherapeutic agents or cannot tolerate their side effects are considered “refractory.” Previous experiments using rats with experimental autoimmune MG suggested that complete elimination of the existing immune system and replacement by means of bone marrow transplantation could cure MG. It is now known that immunoablative treatment with high-dose cyclophosphamide does not damage hematopoietic “stem cells,” permitting repopulation of the immune system without bone marrow transplant. Recent evidence indicates that this treatment can induce durable remissions in autoimmune diseases. In this study, the authors treated three myasthenic patients, for whom treatment with thymectomy, plasmapheresis, and conventional immunotherapeutic agents failed, using high-dose cyclophosphamide (50 mg/kg/day intravenously for 4 days) followed by granulocyte colony-stimulating factor. All three patients tolerated the treatment well and had marked improvement in myasthenic weakness, permitting reduction of immunosuppressive medication to minimal levels. Acetylcholine receptor (AchR) antibody levels decreased in two AChR antibody-positive patients, and anti-MuSK antibody levels decreased in one “AChR antibody-negative” patient. The patients were followed for up to 3.5 years, with no recurrence of symptoms. The authors conclude that high-dose cyclophosphamide treatment appears to be an effective and safe treatment for selected patients with refractory MG. Further follow-up of these and additional patients will be needed to determine whether the benefit is durable.—Valérie Biousse