AHSCT follwoup over 6 years

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AHSCT follwoup over 6 years

Postby Frank » Wed Apr 23, 2008 8:27 am

26 Patients were followed over diffent periods of time (3-72month).
In the whole group only one new lesion has been seen on MRI.
In contrast 16 patients worsend (9 by >1 EDSS), 4 improved (1 by >1 EDSS).

Quite disappointing in my eyes...

--Frank

http://www.abstracts2view.com/aan2008ch ... 8L_P02.162
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Postby gwa » Wed Apr 23, 2008 10:57 am

This is not surprising, Frank. The median
EDSS was 7 and there was only 1 RRMS person in the study.

All of the rest were PPMS or SPMS, both types which respond to nothing anyway, so it would have been more surprising if the results were better.



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HDIT/ACST Trial Results

Postby Shayk » Wed Apr 23, 2008 7:28 pm

Frank

Thanks for posting this. I don’t think the results look so good either and GWA I agree with you that nothing so far has proven effective for SPMS or PPMS.

I don’t know if this article will help in the interpretation of the results, but I saw it during the free access to the MS Journal (available through April) and thought it may help a little. The purpose of the study was to establish a baseline to help assess the risks/benefits of HDIT/ASCT in a clinical trial.

Survival and time to an advanced disease state or progression, of untreated patients with moderately severe multiple sclerosis in a multicenter observational database: relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation

Estimated probability of disease progression (increase in EDSS of 1 or more sustained for 180 days) in this sample (EDSS scores of 3.0-5.5 at baseline) was:

· 5% after one year

· 14% after two years

· 22% after three years

· 38% after five years

· 57% after 10 years, and

· More than 80% after 20 years of observation

So, my understanding of this (as one example) is that after 5 years, more than 60% of untreated people with a baseline EDSS score of 3.0-5.5 would not be expected to experience an increase of 1 or more on the EDSS. Or conversely, fewer than 40% of people would be expected to experience an increase of more than 1 on their EDSS over the course of 5 years or more.

Since more than 50% of the HDIT/ACST trial patients worsened on their EDSS over the course of 5+ years–a question would seem to be not only were the results disappointing, but was HDIT/ACST possibly detrimental? Although the participants in these studies aren’t exactly comparable I think one has to at least ask the question.

At best, roughly comparing these two different studies, HDIT/ACST doesn’t seem to be any better than “placebo“, at least as far as I understand it.

Other comments or observations anyone?

Sharon
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Re: HDIT/ACST Trial Results

Postby rainer » Wed Apr 23, 2008 8:05 pm


At best, roughly comparing these two different studies, HDIT/ACST doesn’t seem to be any better than “placebo“, at least as far as I understand it.

Other comments or observations anyone?

Sharon


Would need to know what the classification of MS the patients int the 2nd study had to compare the two.

That first study is disappointing but fwiw the procedures involved in ACST are not always consistent from one study to the next.
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Postby gwa » Wed Apr 23, 2008 8:07 pm

I am starting to wonder if research is directed toward RRMS so much because the people with SPMS OR PPMS have not responded to anything and it may be more difficult to get funding for research for these types of patients.

The fact that the cause is still unknown is also a big roadblock to finding suitable therapies.

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Postby Shayk » Wed Apr 23, 2008 8:22 pm

Rainer
Would need to know what the classification of MS the patients int the 2nd study had to compare the two
Why?

GWA

I suspect like you that it's difficult to get funding for clinical trials for progressive phases of MS, precisely because they don't know the cause or the pathology and so far they seem to be striking out.

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Postby rainer » Wed Apr 23, 2008 9:36 pm

Shayk wrote:Rainer
Would need to know what the classification of MS the patients int the 2nd study had to compare the two
Why?



Because some MS patients with RRMS who have rapidly advanced in disability respond remarkably well to ACST.

And if the second study was done on a level more proportional to the actual MS population, it's representation of MS types would be much different then the first.
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Postby Shayk » Thu Apr 24, 2008 7:36 pm

Thanks Rainer

I'm not really all that familiar with the ASCT trials. It's good to know that some people who've advanced rapidly in disability did so well with ASCT. I do think that resolution of inflammation can bring dramatic improvements, I'm less certain that it stops disease progression, which is what I tend to be most concerned about.

You're definitely right, the representation of MS "types" was probably different between the two studies. I've just never quite figured out what relevance or significance these "types" have other than to serve as "descriptors" of how the disease is experienced.

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Postby rainer » Fri Apr 25, 2008 7:07 pm

Shayk wrote: I do think that resolution of inflammation can bring dramatic improvements, I'm less certain that it stops disease progression, which is what I tend to be most concerned about.


I think you are right about the inflammation being key to the dramatic improvements. The one thing I'd say about progression is that other MS drugs thought to treat inflammation *do* slow disability (albeit not very well.) Untying the good inflammation/bad inflammation/underlying cause knot is well beyond me though.
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PPMS results

Postby spiff » Fri Apr 25, 2008 8:02 pm

These results are not what someone with PPMs wants to hear. I was DX'd ten years ago and have heard the same story over and overagain. Isn't it about time to take a different approach? From what I can see it's the same thing over and over with different results expected each time. How can anyone ever solve the problem when the cause is unknown?

Find the cause/find the cure.

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Postby Frank » Sat Apr 26, 2008 1:55 am

Thats a very interesting study, thanks Sharon!
I wouldnt have thought that "only" 43% tend to get worse >=1 EDSS after 10 years.

--Frank
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Re: PPMS results

Postby marcstck » Sat Apr 26, 2008 1:07 pm

spiff wrote:These results are not what someone with PPMs wants to hear. I was DX'd ten years ago and have heard the same story over and overagain. Isn't it about time to take a different approach? From what I can see it's the same thing over and over with different results expected each time. How can anyone ever solve the problem when the cause is unknown?

Find the cause/find the cure.

spiff


Results such as those discussed here, and the recent failing of Rituxan in its PPMS trials, seem to point very distinctly to the fact that PPMS is not an immune modulated disease. Immuno ablation and immunosuppression have proven to have very little effect on PPMS patients, yet these methods and others of their ilk are continuously tried time and time again, all to unceasingly negative results. It's about time medical science took its head out of the sand and realized that the progressive form of MSis not going to be addressed by drugs or therapies that manipulate the immune system.

There has to be some other mechanism at work that is causing the cell death that we see in PPMS. SPMS may or may not be yet another beast. Clearly though, this dead horse has been beaten beyond recognition...
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Thank you

Postby spiff » Sat Apr 26, 2008 2:10 pm

Thank you for your elegant reply.

I am too frustrated to be tactful...researchers should concentrate on how to fix the damn problem and move on to ther things to research. They can get rich there!!!!!!!!!!!!!

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