Journal
MYASTHENIA GRAVIS AND RELATED DISORDERS: 11TH INTERNATIONAL CONFERENCE
Volume 1132, Issue -, Pages 305-314Publisher
WILEY-BLACKWELL
DOI: 10.1196/annals.1405.033
Keywords
myasthenia gravis; refractory MG; high-dose cyclophosphamide; Hi Cy; rebooting the immune system; TRECs; autoimmunity; immunotherapy
Funding
- NCI NIH HHS [P01 CA 70970, P01 CA070970] Funding Source: Medline
- NHLBI NIH HHS [T32 HL007525, T32 HL007525-24] Funding Source: Medline
- NINDS NIH HHS [R01 NS040778-04, R01 NS040778] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P01CA070970] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007525] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS040778] Funding Source: NIH RePORTER
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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.
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