PML cases now reach 430

A board to discuss the newly-released drug Tysabri, (formerly known as Antegren) as a treatment for Multiple Sclerosis

PML cases now reach 430

Postby HarryZ » Sat Jan 25, 2014 9:39 am

Latest "reported" cases of PML has risen by 7 last month to 430. Not known if any more related deaths.

http://chefarztfrau.de/?page_id=716
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Re: PML cases now reach 430

Postby CureOrBust » Sat Jan 25, 2014 8:21 pm

By 7 more, the 430 are DEATHS not "simply" CASES of PML. I would guess that cases of PML would be much higher, with deaths only occurring in a smaller percentage of PML cases. As I am sure you know already, PML is no picnic even if you survive.
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Re: PML cases now reach 430

Postby HarryZ » Sun Jan 26, 2014 7:09 am

CureOrBust wrote:By 7 more, the 430 are DEATHS not "simply" CASES of PML. I would guess that cases of PML would be much higher, with deaths only occurring in a smaller percentage of PML cases. As I am sure you know already, PML is no picnic even if you survive.


Can't disagree with what you said, Cure! We know from posts done by Cheer that the number of PML related cases to MS are likely very much higher. And I shake my head when the people from Biogen tell us that PML is not the death sentence it once was??!! Talk about a marketing spin trying to diminish the dangers of using Tysabri.

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Re: PML cases now reach 430

Postby cheerleader » Sun Jan 26, 2014 6:53 pm

On Jan, 22, 2014: 90,294 people reported to have side effects when taking Tysabri. Among them, 2,583 people (2.86%) have PML.
http://www.ehealthme.com/ds/tysabri/pml


On Dec, 29, 2013: 90,291 people reported to have side effects when taking Tysabri. Among them, 665 people (0.74%) have died.
http://www.ehealthme.com/ds/tysabri/death

...and, a new concern. Primary central nervous system lymphoma (PCNSL) from Tysabri use. It's showing up more and more.

http://www.ncbi.nlm.nih.gov/pubmed/24373819
http://msj.sagepub.com/content/18/11/1653.extract
http://onlinelibrary.wiley.com/doi/10.1 ... 2/abstract
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http://ccsviinms.blogspot.com
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Re: PML cases now reach 430

Postby HarryZ » Sun Jan 26, 2014 8:05 pm

...and, a new concern. Primary central nervous system lymphoma (PCNSL) from Tysabri use. It's showing up more and more.

http://www.ncbi.nlm.nih.gov/pubmed/24373819
http://msj.sagepub.com/content/18/11/1653.extract
http://onlinelibrary.wiley.com/doi/10.1 ... 2/abstract


Hi Cheer,

There is likely to be more and more cancers showing up after long term use with Tysabri. This is one potent immune system altering drug that is going to cause havoc with many of the patients that use it. Pretty scary when you start to research it in detail.

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Re: PML cases now reach 430

Postby Anonymoose » Sun Jan 26, 2014 8:37 pm

cheerleader wrote:On Jan, 22, 2014: 90,294 people reported to have side effects when taking Tysabri. Among them, 2,583 people (2.86%) have PML.
http://www.ehealthme.com/ds/tysabri/pml


On Dec, 29, 2013: 90,291 people reported to have side effects when taking Tysabri. Among them, 665 people (0.74%) have died.
http://www.ehealthme.com/ds/tysabri/death

...and, a new concern. Primary central nervous system lymphoma (PCNSL) from Tysabri use. It's showing up more and more.

http://www.ncbi.nlm.nih.gov/pubmed/24373819
http://msj.sagepub.com/content/18/11/1653.extract
http://onlinelibrary.wiley.com/doi/10.1 ... 2/abstract

Hi cheer,
I've been playing with the idea that ms might be or become an "under control" B cell lymphoma (ebv related??) of the CNS. And sometime in the past few days I ran into papers linking pcnsl to vascular issues in the brain. Now you post links to papers showing that tysabri, a drug that keeps lymphocytes from penetrating organs and therefore undercuts the immune system's ability to fight cancer, can cause pcnsl. Since I am a completely unqualified dabbler making random connections, I was wondering what your much more qualified opinion might be regarding the idea that ms might be long term "mini-cancer." Maybe there is a cancer spectrum akin to the autism spectrum? I know this doesn't really belong here but it seemed the easiest place for the conversation. :) Would love to hear/read your thoughts.
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Re: PML cases now reach 430

Postby NHE » Mon Jan 27, 2014 4:08 am

Anonymoose wrote:I've been playing with the idea that ms might be or become an "under control" B cell lymphoma (ebv related??) of the CNS. And sometime in the past few days I ran into papers linking pcnsl to vascular issues in the brain. Now you post links to papers showing that tysabri, a drug that keeps lymphocytes from penetrating organs and therefore undercuts the immune system's ability to fight cancer, can cause pcnsl. Since I am a completely unqualified dabbler making random connections, I was wondering what your much more qualified opinion might be regarding the idea that ms might be long term "mini-cancer." Maybe there is a cancer spectrum akin to the autism spectrum? I know this doesn't really belong here but it seemed the easiest place for the conversation. :) Would love to hear/read your thoughts.


I suspect that PCNSL is a consequence of keeping the immune system out of the CNS in that rogue precancerous cells are not removed, but are allowed to multiply.
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Re: PML cases now reach 430

Postby Anonymoose » Mon Jan 27, 2014 8:58 am

NHE wrote:I suspect that PCNSL is a consequence of keeping the immune system out of the CNS in that rogue precancerous cells are not removed, but are allowed to multiply.

Still thinking this through and need to stop researching on my phone so I keep better track of links. Of course it makes sense that the immune suppression would allow precancerous cells to flourish. Are ebv immortalized B cells considered precancerous as they can be the cause of lymphomas? Tysabri increases circulating peripheral B cells. And in those it doesn't work for, B cells are significantly increased in csf as well. When you quit tysabri, you get the rebound...is this the kill off of all the B cells I suspect are "bad?" The reduction in lesions is simply the result of the peripheral immune system not helping the "CNS immune system" (had that been defined yet?) fight off the spread of ms source?

Since there are so few reported cases of tysabri related pcnsl, it does seem those who develop it must have an extra contributing factor...

Tysabri related pcnsl has been reported in people with crohns, ra, etc as well. So it's not just an ms thing.

As usual, too many questions.
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Re: PML cases now reach 430

Postby cheerleader » Mon Jan 27, 2014 3:34 pm

Hi Anonymoose--
I am, by no means, a doctor or even close...but like you, I read way too much stuff on pub med :)

PCNSL is much more common in people who have AIDS. NHE pretty much called it...it's more about immune suppression in the CNS.

AIDS-related PCNSL (AIDS-PCNSL) is an aggressive non-Hodgkins's lymphoma (NHL) accounting for 20% of all AIDS-NHL that arises and is exclusively contained within the CNS (1) (2). Most AIDS-PCNSLs are histologically classified as either diffuse large cell or large cell immunoblastic lymphomas of B cell origin. Differences between PCNSL and systemic NHL in AIDS patients are well described (3) and include histological, genetic, immunophenotypic and clinical characteristics that suggest distinct pathogenic mechanisms. Estimates place the incidence of AIDS-PCNSL at 2-13% of all AIDS patients with profound immunosuppression being a common feature


The pathogenesis of PCNSL is complex and multifactorial and remains ill-defined. HIV does not induce lymphoma via direct infection of B cells. Rather, HIV-induced immunosuppression, chronic B cell stimulation and cytokine dysregulation may facilitate genetically unstable oligoclonal B cell expansions and, in turn, predispose cells to malignant transformation (3)

http://aidscience.org/neuroaids/article ... 2(2%29.asp

And the reason we have so few cases dx in Tysabri use....it's really sad, actually.
Over 1/2 of all PCNSL cases are diagnosed on autopsy.
The cases found in Tysabri users were in people who were still alive.
I'm not even sure Biogen is reporting on this at all.
It's all so depressing to me....how pwMS continue to be used as lab rats, while pharma gets fat.
ugh,
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Re: PML cases now reach 430

Postby Anonymoose » Mon Jan 27, 2014 4:42 pm

Quick stop before making dinner...

I thought tysabri induced pcnsl was more similar to that seen in elderly than that seen in pwAIDS. I didn't bookmark that paper but can look it up tomorrow if you want links.

Another wrench to throw into the works...pcnsl imitates ms. Maybe some who are diagnosed with ms, particularly the ones who need constant steroids have pcnsl and not ms?
http://www.ncbi.nlm.nih.gov/m/pubmed/2262803/ (miracle! I have a link!)

Thanks for the feedback. You may not be a doctor but you are waaay further along in this than I am. :)
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Re: PML cases now reach 430

Postby Anonymoose » Mon Jan 27, 2014 7:49 pm

Googling for dessert. :)

I'm not the only one who suspects a connection between lymphoma and ms...
http://www.neuro.org.tw/magz/doc/dw2008 ... %20p92.pdf

Apparently, pcnsl occurs in msers without tysabri. Interesting!
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Re: PML cases now reach 430

Postby cheerleader » Mon Jan 27, 2014 8:47 pm

Anonymoose wrote:Googling for dessert. :)
I'm not the only one who suspects a connection between lymphoma and ms...
http://www.neuro.org.tw/magz/doc/dw2008 ... %20p92.pdf
Apparently, pcnsl occurs in msers without tysabri. Interesting!


It is interesting...the researchers state that in this one case, they believe the use of immune modulating meds as an MS patient may have contributed to the PCNSL. Hard to know. Some researchers have found more risk of brain cancer for those with MS.
http://www.medicalnewstoday.com/articles/247220.php

The researchers also found that MS patients who developed cancer usually had larger tumors at time of diagnosis. They state that more researcher is needed to find out why some tumors might be caught later in individuals with MS.
Helen Tremlett, associate professor in the UBC Faculty of Medicine, said: "Because the symptoms of MS can be broad and include feelings of fatigue, it's possible the symptoms of cancer are being masked or overlooked."


It could all be coincidental...it could be B cells, it could be a faulty blood brain barrier.

I liked the BNAC research that said the link with MS to EBV, Lyme, cpn, and a variety of viruses and bacteria might be due to stagnation.
The association between EBV infection and CCSVI has not yet been explored; however, it could be hypothesized that venous stasis in the superior saggital sinus due to extracranial outflow impairment could affect the drainage of bridging veins that pass through the subarachnoid space (near the meninges and EBV-infected B-cell follicles) and contribute to EBV activation. The venous stasis hypothesis in the SSS may contribute to understanding why so many different viruses and bacteria [3,111] have been linked to increased MS susceptibility risk over the last 50 years.

http://www.expert-reviews.com/doi/abs/1 ... ern.11.117

Anyhoo...to get back on topic of Tysabri :)
If MS really does compromise the blood brain barrier, the last thing people should be doing is taking these severe immunosuppressant drugs. But that's just my opinion....
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Re: PML cases now reach 430

Postby CureOrBust » Tue Jan 28, 2014 3:38 am

cheerleader wrote:Anyhoo...to get back on topic of Tysabri :)
If MS really does compromise the blood brain barrier, the last thing people should be doing is taking these severe immunosuppressant drugs. But that's just my opinion....
My understanding of Tysabri is that it works by blocking a "selective" part of the immune system from entering / passing the BBB (and hence CNS specific infections of JCV ie PML develop). It may have some immune action elsewhere, but its the blocking of the immune system to the CNS that it relies on for its effectiveness.

https://en.wikipedia.org/wiki/Natalizumab
Natalizumab is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin. Natalizumab is used in the treatment of multiple sclerosis and Crohn's disease.
...
The drug is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood–brain barrier


I'm not on Tysabri's side, and rejected the treatment when it was offered to me personally, because of the possibility of PML.
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Re: PML cases now reach 430

Postby CureOrBust » Fri Jan 31, 2014 7:38 pm

This was news to me:

Unfortunately, the sudden removal of natalizumab often triggers a condition called immune reconstitution inflammatory syndrome (IRIS), which is practically as dangerous as PML. Many of the deaths and persistent deficits attributed to PML actually are a consequence of IRIS.
http://www.ms-uk.org/tysabri
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