Rebooting the immune system with high-dose cyclophosphamide for treatment of refractory myasthenia gravis

Daniel B. Drachman, Robert N. Adams, Rong Hu, Richard J. Jones, Robert A. Brodsky

Research output: Chapter in Book/Report/Conference proceedingConference contribution

79 Scopus citations


A small but important proportion of patients with myasthenia gravis (MG) are refractory to conventional immunotherapy. We have treated 12 such patients by "rebooting" the immune system with high-dose cyclophosphamide (Hi Cy, 200 mg/kg), which largely eliminates the mature immune system, while leaving hematopoietic precursors intact. The objective of this report is to describe the clinical and immunologic results of Hi Cy treatment of refractory MG. We have followed 12 patients clinically for 1-9 years, and have analyzed their humoral and cellular immunologic parameters. Hi Cy is safe and effective. All but one of the patients experienced dramatic clinical improvement for variable periods from 5 months to 7.5 years, lasting for more than 1 year in seven of the patients. Two patients are still in treatment-free remission at 5.5 and 7.5 years, and five have achieved responsiveness to immunosuppressive agents that were previously ineffective. Hi Cy typically reduced, but did not completely eliminate, antibodies to the autoantigen AChR or to tetanus or diphtheria toxin; re-immunization with tetanus or diphtheria toxoid increased the antibody levels. Despite prior thymectomy, T cell receptor excision circles, generally considered to reflect thymic emigrant T cells, were produced by all patients. Hi Cy treatment results in effective, but often not permanent, remission in most refractory myasthenic patients, suggesting that the immune system is in fact "rebooted," but not "reformatted." We therefore recommend that treatment of refractory MG with Hi Cy be followed with maintenance immunotherapy.

Original languageEnglish (US)
Title of host publicationMyasthenia Gravis and Related Disorders 11th International Conference
PublisherBlackwell Publishing Inc.
Number of pages10
ISBN (Print)9781573316873
StatePublished - Jun 2008

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Autoimmunity
  • Hi Cy
  • High-dose cyclophosphamide
  • Immunotherapy
  • Myasthenia gravis
  • Rebooting the immune system
  • Refractory MG
  • TRECs

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science


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