Intravenous cyclophosphamide monthly pulses in refractory myasthenia gravis

  • Enrique Gomez-Figueroa
  • Sofía Garcia-Trejo
  • Lisette Bazan-Rodriguez
  • Roberto Cervantes-Uribe
  • German Chac-Lezama
  • Juan Carlos López-Hernández
  • Steven Vargas-CañasEmail author
Original Communication



Refractory myasthenia gravis (MG) is defined as a failure to respond adequately to conventional therapies, the inability to reduce immunosuppressive therapy without clinical relapse or the need for ongoing rescue therapy, severe adverse effects from immunosuppressive therapy (treatment intolerant) or frequent myasthenic crisis even on therapy. Cyclophosphamide (CYC) is a DNA alkylating agent that causes important interference in transcription processes and DNA replication, it has been used in refractory MG with controversial results. We aim to determine the efficacy of CYC in refractory MG in the Mexican population.


In an observational, longitudinal retrospective study, we identified eight refractory MG patients treated with 30–50 mg/kg monthly CYC for at least 6 months. The efficacy was assessed by Osserman scale considering significant improvement a ≥ 1 point reduction and Myasthenia Gravis Composite Scale. The relapse-free and remission-free period were also calculated using the Kaplan–Meier statistic.


Clinical improvement was achieved in 75% of the patients. According to the Kaplan–Meier analysis, the median progression-free survival (PFS) was 9 (6.2–11.5) months and the median time to progression (TTP) was 4 (1–8) months. Response was independent of patient's characteristics, except for the MG age of onset (p = 0.0025).


CYC was effective in all patients with refractory MG for a mean of 9 months, with worsening thereafter, which could be associated with low cumulative dose. The symptomatic improvement with CYC was noted within the 1st month. We conclude that CYC is effective as an induction to remission therapy, although our data suggest it is not effective as a long-term therapy.


Author contributions

Contributions V-C and L-H were in charge of the diagnosis, treatment care and follow up of the patient and supervised the elaboration of the manuscript. G-F and B-R data analysis and organization. G-T, C-U and C-L prepared the draft.

Compliance with ethical standards

Conflicts of interest

All authors declare no competing interests or external funding.

Ethical standards

Authors have read the journal's position on issues involved in ethical publication. This study was approved by the research ethics committee of our institution.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Enrique Gomez-Figueroa
    • 1
  • Sofía Garcia-Trejo
    • 1
  • Lisette Bazan-Rodriguez
    • 1
  • Roberto Cervantes-Uribe
    • 1
  • German Chac-Lezama
    • 1
  • Juan Carlos López-Hernández
    • 1
  • Steven Vargas-Cañas
    • 1
    Email author
  1. 1.Neurology DepartmentInstituto Nacional de Neurología Y Neurocirugía Manuel Velasco SuarezMexico CityMexico

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