{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:39:29Z","timestamp":1782290369500,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>A small but important proportion of patients with myasthenia gravis (MG) are refractory to conventional immunotherapy. We have treated 12 such patients by \u201crebooting\u201d the immune system with high\u2010dose cyclophosphamide (Hi Cy, 200\u2003mg\/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\u20139\u2003years, 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\u2003months to 7.5\u2003years, lasting for more than 1\u2003year in seven of the patients. Two patients are still in treatment\u2010free remission at 5.5 and 7.5\u2003years, 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\u2010immunization 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 \u201crebooted,\u201d but not \u201creformatted.\u201d We therefore recommend that treatment of refractory MG with Hi Cy be followed with maintenance immunotherapy.<\/jats:p>","DOI":"10.1196\/annals.1405.033","type":"journal-article","created":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T23:23:28Z","timestamp":1214004208000},"page":"305-314","source":"Crossref","is-referenced-by-count":75,"title":["<i>Rebooting the Immune System with High\u2010Dose Cyclophosphamide for Treatment of Refractory Myasthenia Gravis<\/i>"],"prefix":"10.1111","volume":"1132","author":[{"given":"Daniel B.","family":"Drachman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Brodsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406233302507"},{"key":"e_1_2_8_3_2","first-page":"159","article-title":"Myasthenia gravis","volume":"88","author":"Vincent A.","year":"2002","journal-title":"Adv. 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