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Treatment of refractory myasthenia: “Rebooting” with high‐dose cyclophosphamide
Author(s) -
Drachman Daniel B.,
Jones Richard J.,
Brodsky Robert A.
Publication year - 2003
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10400
Subject(s) - medicine , cyclophosphamide , myasthenia gravis , thymectomy , refractory (planetary science) , plasmapheresis , bone marrow , gastroenterology , chemotherapy , antibody , surgery , immunology , physics , astrobiology
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.