PMID- 31139690
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20220408
IS  - 2328-9503 (Print)
IS  - 2328-9503 (Electronic)
IS  - 2328-9503 (Linking)
VI  - 6
IP  - 5
DP  - 2019 May
TI  - Treatment of natalizumab-associated PML with filgrastim.
PG  - 923-931
LID - 10.1002/acn3.776 [doi]
AB  - OBJECTIVE: There is no consensus on the treatment of progressive multifocal 
      leukoencephalopathy (PML) occurring in multiple sclerosis (MS) patients treated 
      with natalizumab (Nz). We report novel immune activating treatment with 
      filgrastim of Nz-associated PML in MS patients treated at Rush University Medical 
      Center. METHODS: We retrospectively analyzed 17 Nz-PML patients treated at this 
      single tertiary referral center between 2010 and 2017. We reviewed the clinical 
      symptoms, diagnostic methods, survival, outcome and MS modifying therapy (MSMT) 
      after Nz-PML. RESULTS: PML occurred after an average of 49 Nz infusions. To 
      facilitate JCV elimination by accelerating immune reconstitution inflammatory 
      syndrome (IRIS), all patients received subcutaneous filgrastim upon PML diagnosis 
      and discontinuation of Nz; eight received plasma exchange (PLEX). Earlier than 
      previously published, PML-IRIS occurred in 15 of 17 (88.2%) patients within a 
      mean of 57.4 days (SD 21.20) after the last Nz infusion. Seven patients recovered 
      to or near baseline. There were no PML/IRIS-related fatalities but one patient 
      committed suicide 2.5 years 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 MSMTs after Nz-PML on an average of 26 months after Nz 
      withdrawal. INTERPRETATION: Our findings indicate that immunoactivation with 
      filgrastim during PML and careful management of subsequent IRIS is likely 
      beneficial in patients with Nz-PML, without worsening MS. The clinical course of 
      MS may be ameliorated by PML.
FAU - Stefoski, Dusan
AU  - Stefoski D
AD  - Department of Neurological Sciences Rush University Medical Center Chicago 
      Illinois.
FAU - Balabanov, Roumen
AU  - Balabanov R
AD  - Department of Neurology Northwestern University Chicago Illinois.
FAU - Waheed, Rasha
AU  - Waheed R
AD  - Department of Neurological Sciences Rush University Medical Center Chicago 
      Illinois.
FAU - Ko, Michael
AU  - Ko M
AD  - Department of Neurological Sciences Rush University Medical Center Chicago 
      Illinois.
FAU - Koralnik, Igor J
AU  - Koralnik IJ
AD  - Department of Neurological Sciences Rush University Medical Center Chicago 
      Illinois.
FAU - Sierra Morales, Fabian
AU  - Sierra Morales F
AD  - Department of Neurological Sciences Rush University Medical Center Chicago 
      Illinois.
LA  - eng
GR  - R01 NS047029/NS/NINDS NIH HHS/United States
GR  - R01 NS074995/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20190408
PL  - United States
TA  - Ann Clin Transl Neurol
JT  - Annals of clinical and translational neurology
JID - 101623278
RN  - 0 (Immunologic Factors)
RN  - 0 (Natalizumab)
RN  - PVI5M0M1GW (Filgrastim)
CIN - J Neurol. 2019 Oct;266(10):2587-2589. PMID: 31422455
MH  - Adult
MH  - Brain/diagnostic imaging
MH  - Disease Progression
MH  - Female
MH  - Filgrastim/*therapeutic use
MH  - Humans
MH  - Immunologic Factors/*adverse effects
MH  - JC Virus/*drug effects
MH  - Leukoencephalopathy, Progressive Multifocal/diagnostic imaging/*drug 
      therapy/*etiology
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Multiple Sclerosis/*drug therapy
MH  - Natalizumab/*adverse effects/therapeutic use
MH  - Retrospective Studies
PMC - PMC6529830
COIS- The authors have no additional financial relationships or conflicts of interest 
      relevant to this article to disclose.
EDAT- 2019/05/30 06:00
MHDA- 2019/05/30 06:01
PMCR- 2019/04/08
CRDT- 2019/05/30 06:00
PHST- 2018/11/21 00:00 [received]
PHST- 2019/03/18 00:00 [revised]
PHST- 2019/03/20 00:00 [accepted]
PHST- 2019/05/30 06:00 [entrez]
PHST- 2019/05/30 06:00 [pubmed]
PHST- 2019/05/30 06:01 [medline]
PHST- 2019/04/08 00:00 [pmc-release]
AID - ACN3776 [pii]
AID - 10.1002/acn3.776 [doi]
PST - epublish
SO  - Ann Clin Transl Neurol. 2019 Apr 8;6(5):923-931. doi: 10.1002/acn3.776. 
      eCollection 2019 May.