PML on Alemtuzumab

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Immune profiling of a patient with alemtuzumab-associated progressive multifocal leukoencephalopathy.

Gerevini S, Capra R, Bertoli D, Sottini A, Imberti L.

Mult Scler. 2019 Apr 9:1352458519832259. 

A 31-year-old woman affected by multiple sclerosis (MS) experienced generalized tonic-clonic seizures 2 months after the second alemtuzumab cycle. Positive JC virus (JCV)-DNA in cerebrospinal fluid (CSF) and lesion iconography at magnetic resonance imaging (MRI) were suggestive of progressive multifocal leukoencephalopathy (PML). After 1 month, during full-blown immune reconstitution inflammatory syndrome, JCV-DNA became negative and symptoms gradually improved. New T- and B-cell output and T- and B-cell diversity were low and lymphocytes poorly responded to stimulation. This is the first case of an alemtuzumab-treated patient with clinical symptoms and radiological features compatible with PML. The lack of large T- and B-cell diversity, necessary for JCV recognition, is likely to have concurred to PML insurgence.

This person had been treated with alemtuzumab and developed PML 14 months after the intial course so hard to suggest this is carry over PML course. Now this is not good news but it does suggest something, because this person did not die of PML as occurred in a previous case of carry-over PML, meaning that they had enough immune cells to deal with the virus, if fact they got attack of the virus by the immune system, indicating that once the drug is gone, which lasts about 2 weeks, immune responses can be generated. This supports the idea that there is not a large window of immunosuppression with alemtuzumab.

Maybe ProfG will come out of retirement to tell us about this case as I am sure Genzyme have been briefing about this

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MouseDoctor

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  • Prof g input on the blog is rather erratic to say the least

    So is that the end of neurologist input?

    And what has happened to those webinar sessions which you did addressing hsct a couple of months ago?

  • The question can be asked differently: what is the point of this blog sans Gavin?

    I am giving it another 3 months after 8 years of weekly following. The ball is in your court to engage with Klaus, Ben or other senior and opinionated clinicians or see this blog morph into a mouse blog.

    • And what’s up with the last Guest post? Really, we are down to amateurs asking for a say? Is this now the Farage Populist Approach to MS?

      I am not meaning to poo poo on the guest for sharing his views, but his view of empowerment is erroneous in my view (but then again, no one should care about my views neither). I did a 7 point rebuttal in the comment section of his post.

  • “Immunodeficiency or immunosuppression allows JCV to reactivate. In the brain, it causes the usually fatal progressive multifocal leukoencephalopathy, or PML, by destroying oligodendrocytes. Whether this represents the reactivation of JCV within the CNS or seeding of newly reactivated JCV via blood or lymphatics is unknown.”

    This happen in Immunodeficiency or immunosuppression patients

    This report describes an unfortunate case of PML in a recipient of an allogeneic stem cell transplant for acute myelogenous leukemia. The JC virus was undetectable in the patient’s cerebrospinal fluid by polymerase chain reaction (PCR); however, a positive diagnosis was made after a brain biopsy. This and other published cases demonstrate that recipients of allogeneic stem cells can develop PML. Moreover, early diagnosis of the disease is often difficult and, as demonstrated in this case, screening with PCR does not appear to have strong diagnostic significance. With no effective treatment presently available, restoration of immune function is the only intervention that can affect prognosis

    Progressive multifocal leukoencephalopathy after allogeneic stem cell transplantation: Case report and review of the literature.
    https://www.ncbi.nlm.nih.gov/pubmed/29512846

    Maybe age could make maters worse

    ” Multivariate analysis confirmed age to be the only significant predictive factor for JCPyV reactivation”

    JC polyomavirus reactivation is common following allogeneic stem cell transplantation and its preemptive detection may prevent lethal complications.

    “MS has been proposed as a model of precocious immunosenescence, and the age of MS
    patients has emerged as an important risk factor for
    PML.

    Immune profiling of a patient with
    alemtuzumab-associated progressive
    multifocal leukoencephalopathy

    Mills EA and Mao-Draayer Y. Aging and lymphocyte
    changes by immunomodulatory therapies impact
    PML risk in multiple sclerosis patients. Mult Scler
    2018; 24(8): 1014–1022

    Despite thestronganti-JCVantibody
    responses seenbeforeoratPMLdiagno-
    sis, impairedBcellfunctionmayincrease
    the riskofdevelopingPML.PMLcases
    have beenreportedduringrituximab
    (CD20-targeting monoclonalantibody)
    treatment outsidetheMS field [5], and
    studies haveshownthatnatalizumabther-
    apy canimpairthehomingofpre-BandB
    cells intonaturalniches.Thisisassociated
    with asuppressiveeffectofnatalizumab
    on antibodyproduction(decreasedlevels
    of IgGandIgMinbloodandCSF,intra-
    thecally producedtotalandvirus-specific
    IgG, andoligoclonalbandintensity) [10],

    and couldimpacttheantigen-presenting
    functions ofBcells.

    PML: TheDarkSide
    of Immunotherapyin
    Multiple Sclerosis

    Finally PD-1 blockade could be useful strategy

    https://www.nejm.org/doi/10.1056/NEJMoa1815039

    Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy

    Obriagdo

  • Prof G has been accused of abusing the Barts-MS blog and using it as a platform to promote himself. He will continue to post on this platform but will be limiting his posts to factual content and not random personal musings and off-beat MS topics. He has stopped using the name Prof G and will now post under Barts-MS. All personal postings will now be done on Medium.

    • There you go…pointless… why not post as ProfG and save all this anguish…..
      The April Fool has back fired….I am sad to say.

  • Just seen this story on Ms trust about alemtuzumab having temporary restriction under recommendation of e m a

    Do you have any further info and will it affect patients treated with this drug after 4 years?

    • If you are on treatment you would carry on with your next course, maybe ProfG will fill us in when he gets back from his secret weekend trip with MrsG

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