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We report novel immune activating treatment with filgrastim of Nz\u2010associated <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> patients treated at Rush University Medical Center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed 17 Nz\u2010<jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> patients treated at this single tertiary referral center between 2010 and 2017. We reviewed the clinical symptoms, diagnostic methods, survival, outcome and <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> modifying therapy (<jats:styled-content style=\"fixed-case\">MSMT<\/jats:styled-content>) after Nz\u2010<jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> occurred after an average of 49 Nz infusions. To facilitate <jats:styled-content style=\"fixed-case\">JCV<\/jats:styled-content> elimination by accelerating immune reconstitution inflammatory syndrome (<jats:styled-content style=\"fixed-case\">IRIS<\/jats:styled-content>), all patients received subcutaneous filgrastim upon <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> diagnosis and discontinuation of Nz; eight received plasma exchange (<jats:styled-content style=\"fixed-case\">PLEX<\/jats:styled-content>). Earlier than previously published, <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IRIS<\/jats:styled-content> occurred in 15 of 17 (88.2%) patients within a mean of 57.4\u00a0days (<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content> 21.20) after the last Nz infusion. Seven patients recovered to or near baseline. There were no <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">IRIS<\/jats:styled-content>\u2013related fatalities but one patient committed suicide 2.5\u00a0years later. PLEX had no impact on PML outcome. Of 17 patients, 3 (18%) had MS relapses within 1 year after PML, and 5 (29%) beyond 1 year of PML onset, which is lower than expected in highly active MS patients. Eight patients started <jats:styled-content style=\"fixed-case\">MSMT<\/jats:styled-content>s after Nz\u2010<jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> on an average of 26\u00a0months after Nz withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings indicate that immunoactivation with filgrastim during <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> and careful management of subsequent <jats:styled-content style=\"fixed-case\">IRIS<\/jats:styled-content> is likely beneficial in patients with Nz\u2010<jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>, without worsening <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>. The clinical course of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> may be ameliorated by <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.776","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T07:40:06Z","timestamp":1554709206000},"page":"923-931","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Treatment of natalizumab\u2010associated <scp>PML<\/scp> with filgrastim"],"prefix":"10.1002","volume":"6","author":[{"given":"Dusan","family":"Stefoski","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roumen","family":"Balabanov","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Waheed","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor J.","family":"Koralnik","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Sierra Morales","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61620-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0102-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828c2fa1"},{"key":"e_1_2_8_5_1","unstructured":"TYSABRI\u00ae(natalizumab): PML Incidence in Patients Receiving TYSABRI. 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