Dr Brodsky is a Clinical Research Scholar of the Leukemia and Lymphoma Society.
Treatment of refractory myasthenia: “Rebooting” with high-dose cyclophosphamide
Article first published online: 25 NOV 2002
Copyright © 2002 Wiley-Liss, Inc.
Annals of Neurology
Volume 53, Issue 1, pages 29–34, January 2003
How to Cite
Drachman, D. B., Jones, R. J. and Brodsky, R. A. (2003), Treatment of refractory myasthenia: “Rebooting” with high-dose cyclophosphamide. Ann Neurol., 53: 29–34. doi: 10.1002/ana.10400
- Issue published online: 31 DEC 2002
- Article first published online: 25 NOV 2002
- Manuscript Accepted: 23 AUG 2002
- Manuscript Revised: 14 AUG 2002
- Manuscript Received: 1 JUL 2002
- C.W. Parke Family Foundation
- Ann and Donald Brown Family Foundation
- Eleanor Denmead Ingram Foundation
Patients with myasthenia gravis (MG) who do not respond to conventional immunotherapeutic agents, or cannot tolerate their side effects, are considered “refractory.” Ablation of the immune system followed by bone marrow transplant has been shown to cure experimental MG in rats. 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. We treated three myasthenic patients, for whom treatment with thymectomy, plasmapheresis, and conventional immunotherapeutic agents failed, by using high-dose cyclophosphamide (50mg/kg/day intravenously for 4 days) followed by granulocyte colony stimulating factor. All three patients tolerated the treatment well and have 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 have been followed for up to 3.5 years, with no recurrence of symptoms. 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.