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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.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.
Hi Cheer,...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,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
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.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.
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?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.
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
http://aidscience.org/neuroaids/articles/Neuro2(2%29.aspThe 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)
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.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 could all be coincidental...it could be B cells, it could be a faulty blood brain barrier.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."
http://www.expert-reviews.com/doi/abs/1 ... ern.11.117The 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.
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.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....
I'm not on Tysabri's side, and rejected the treatment when it was offered to me personally, because of the possibility of PML.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
http://www.ms-uk.org/tysabriUnfortunately, 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.