This Is MS Multiple Sclerosis Community: Knowledge & Support

Shucks...I wish you the best of luck with Dr. Burt! I hope that you can get into the trial and that you get "George-like" results. Tried to get my wife into the trial but exceeded that age limitation and she is PPMS so we struck out on 2 counts before even getting started. We did go to RUSH for an appointment with Dr. Dusan Stefoski who is a neuro and he sees several of the paitients Dr. Burts trial. We were just looking for his insight into HSCT in general and then maybe persue it further overseas if he thought it might benefit her. Well, we never got around to discussing HSCT much because he said he doesn't think she has MS....thinks it could be an "MS mimicking" disease. So, now we're working thru all that...he thinks he wants to treat her with "Celcept".

Anybody have any insights with "Celcept"???

Good luck in Chicago Shucks!

Brad in Sarasota

Hi George, you have claimed that 100% of people who have had success with HSCT have had their MS stopped and no one has since regressed. Can you tell me how you found these numbers, or how you found this out? Are you 100% sure? Also, are those who have Burts version similarly cured? Or have any of them regressed years after having the protocol. It sounds so amazing that it feels like it can't be true! Surely there must be some people to whom HSCT has cured them, but after a while it has come back?

I watched a youtube video of a seminar on MS in Australia where the lady speaking compared HSCT to Campath and said that the two procedures show little difference with outcomes...

This is the video: http://www.youtube.com/watch?v=VtBLhgLG ... ure=relmfu

Also, Does Campath stop progression as well? It seems to me that Campath and Burts Myleoblative procedure are quite similar when you get down to what's happening in your body, is this the case?

cheers!

VQ

George's numbers are a little cherry picked, but are true from what I have read. The initial studies were done on sp and pp patients, several of whom progressed later on according to the phase one findings. 85% were progression free at 3 yrs, and 5% had died of TRM of some sort or other. Since the BEAM and non myeleablative procedures have been adopted, and the patients accepted have been limited to rr and EARLY sp patients there have been no deaths, great successes, but some morbidity issues that pop up, such as secondary infection issues that have caused stella (mentioned in another thread) to lose her hearing and fingers and toes. I personally think that her case is due more to her standard of care than to the procedure, but I am a lawyer and not a dr. Either way, it is a serious treatment and deserves serious thought before undertaking. I say this because of the half excited, half scared to death take I have on it right now.
Dr Burt compares campath to hsct in a youtube video you can find, where he says that camath may be able to stop progression for a long time, but his treatment is the only one that allows for any serious recovery of symptoms (defined by a lessening of 1 point on EDSS).
You cant really blame the big companies for their denial of HSCT. It's acceptance would mean the loss of a billion dollar a year industry to drugs that have been around long enough to be generic. They are in business to make money, and campath is a way to do this. It is dangerous, and it is risky, but from what I have read, it is effective. Dave, over at active msers put it this way: (paraphrased)
If a treatment was developed, for free, that could stop MS and cure disability, but killed 30 or 50% of those who tried it, some people would, but I would not. I suspect that guys like George and Asher, and Packo would take a stab at it. I don't know quite where I would be, but I am hopeful that I can raise the cash and convince the guys upthere to take me for this one, where the risk is about 5%.

I hope that answers some questions.

Shucks

_________________
"A gun is a tool, Marian; no better or no worse than any other tool: an axe, a shovel or anything. A gun is as good or as bad as the man using it. Remember that." -- Shane

Who is John Galt?

Shucks, first and foremost, wish you a good meeting with Dr. Burt coming 2/1. I sure hope you will join the HSCT squad soon

Btw, where did you get the 5% mortality rate from? Heidelberg University Hospital has a myeloablative HSCT mortality rate of 'just' 0.84%

Thanks Shucks,

Seeing as you are seeing Burt (congrats by the way), can you tell me if he accepts anyone who can afford to pay for their treatment (I hear this is about $150,000) or do the stringent acceptance clauses still apply, even if you are paying and are outside of the trial?

I recently saw Dr. Burt regarding participation in the MIST trial. He stated that although the trial is not complete and the data has not been thoroughly analyzed, he had great confidence that the efficacy of HSCT treatment to completely stop progression of RRMS is 70% for qualifying participants (meaning a diagnosis of RRMS and demonstrable evidence of the disease being in the inflammatory stage and not in a neurodegenerative stage). He stated that 30% of qualifying RRMS participants experienced a relapse of the disease and they "have no idea why".

Regarding paying for the procedure outside of the study, my understanding from my conversation with him is he will do the procedure for patients that he believes are still in the inflammatory stage of RRMS but do not qualify for the study for some of the many reasons to be excluded. If you qualify for the study you must be subject to the randomized assignment of either the control arm or the transplant arm and you can't pay your way into the transplant arm.

KMG

In my mind their are two different types of autologous HSCT treatments. The non-myeloablative method is just extreme immune suppression, while the myeloablative method restores self tolerance.

Great questions VQ. Some of my comments in reverse order. . . . .

Campath (Alemtuzemaub) is a good drug and has shown good treatment efficacy (far better than the CRAB drugs) and I'm happy to see it come to market. Campath does appear to stop the progression of MS in many (but not all) patients for at least a limited time that it has been studied (about 6 years now). But as a single-agent therapy it's absolutely nowhere near as effective as HSCT which is a multi-agent therapy.

Thanks for the link to the video of Dr. Suzanne Hodgkinson. I watched the entire segment and found her talk regarding drug treatments for MS interesting. She only very briefly mentioned stem cell transplantation near the end (which she referred to in the older vernacular as bone marrow transplantation) and I heard her make the following two comments regarding the subject:

"[HSCT] has not been tested near as carefully as Campath."

- and -

"It's not clear that it [HSCT] offers any particular advantages [over Campath]."

I feel very comfortable in clearly and strongly stating that these remarks are absolutely wrong and flat out false. At first I thought that Dr. Hodgkinson said this out of ignorance which she could be forgiven for. But now that I have checked her background I learned that she may have a major conflict of interest because of her (and her medical doctor husband's) money interest in drug patents and big pharma funding. I really have to question if she has conflicting motivation while lecturing about the subject. (HSCT cannot be patented and cannot be controled by a single entity.) It certainly doesnt help that both she and her husband have been embroiled for years in allegations of possible fraud and confirmed unethical behavior. . . .

http://www.smh.com.au/national/academic ... -87n9.html

HSCT as a treatment for MS has been studied to a far greater extent than Campath. For early RRMS patients Campath has demonstrated a halting of disease progression in 78% of treated patients. Compare that with 100% of halting in the same population of HSCT treated patients, the data is pretty clear. But don't take my word for it. I'll let a better-credentialed doctor explain in the first 45 seconds of this video why HSCT is superior to Campath. . .

http://www.youtube.com/watch?v=msYTOSo4 ... re=channel

Regarding the stopping of MS disease progression following HSCT. . . . I have not seen a 'single' source that makes this statement. Such a claim can only be made due to the absence of any reports that an MS patient has gone on to progress following halting of disease activity via HSCT. I have looked very hard to find such a report, and have found none. So the claim comes from the absence of a report and I continue to keep my eyes open for any reports of anyone that had their MS progress following a halt in their MS via HSCT treatment. I welcome anyone to bring forward such data if it exists but have yet to see anything in this respect. So the evidence that the (halting of disease activity) statement is true by the absence of data to suggest the opposite is occuring. Sorry, that's the way science works.

Regarding the comparison of the curative success rates of the myeloablative vs. non-myeloablative protocols, so far (at 8 or 9 years post-transplantation), both protocols have demonstrated substantially similar curative efficacy (statistically the same). The data for the non-myeloablative protocol only goes out this far (having been first performed in 2002). The myeloablative protocol has been performed specifically for MS since the mid-1990's, so there's well over a decade of experience with this. And a related note. . . since the updated HSCT treatment protocols have been implemented starting with the phase II trials (and now continuing into the phase III trials) there have not been any treatment-related deaths. Not a single one.

Agreed with Asher. Autologous HSCT is not a wildly risky procedure. In fact, at 1:30 into this video Dr. Burt also states "There's very low risk. Less than 1% mortality from the procedure."

http://www.youtube.com/watch?v=Y8SAgUB5 ... r_embedded

Hi George,
Im curious to know what the theory is behind the non-myeloablative method? It seems to me that if all antigen specific cells are not eliminated, there would be a possibility of a continuation of MS by expansion of these cells at some time in the future.

I appreciate your thoughts.

Okay, thanks guys for answering my questions so fast!

So, KMG, Dr. Burt says that it is effective in 70% of RRMS cases, so in 30% they experienced relapses.... is there a time limit on that, like three years out, five years out, or do they just not have any positive effect from it at all? Also is this the fact that it is non-myleoblative? If you have the full on HSCT, will it stop the disease in 100% or closer to 100%?

So George, there's some stats right there, 30% of people who have the non-myleoblative HSCT do in fact relapse. I assume that (hopeful of) the non-myleoblative route could have a higher success rate?

MS is such a complex bastard! They have no idea why the 30% relapse... it just goes to show how far we are from actually getting a handle on the causes of this thing.

Here is an article written by Dr. Burt regarding HSCT for autoimune diseases:

http://www.allmystemcells.com/JAMA_ASC_review.pdf

So, it looks like the purpose of the Nonmyeloablative regimen he developed is to only eliminate antigen specific leukocyctes and does not completely destroy the bone marrow:



This seems more appropriate in regards to the idea of re-establishing self-tolerance. But I still don't know why re-imunization is not required?

So George, there's some stats right there, 30% of people who have the non-myleoblative HSCT do in fact relapse. I assume that (hopeful of) the non-myleoblative route could have a higher success rate?

I have only heard that this is what Dr. Burt mentioned to someone. That's the definition of anecdoteal information. The only data that I use for my comments is scientific in nature, meaning that the data should be published and scientifically peer-reviewed. I have never before heard that Burt's non-myeloablative HSCT protocol fails in 30% of cases. The most recently published phase II trial data clearly indicates the procedure to effectively stop MS progression in 100% of (early RRMS) cases. The next phase III randomized trial is already underway and when the results are published in several years time we'll see if the data agrees.

A summary from Burt's phase II trial (the technical publication is available online with the Lancet):

Stem cells used to reverse MS

http://www.independent.co.uk/life-style ... 20402.html

"Three years after the treatment, carried out between 2003 and 2005, progression of the disease had been halted in all [100%] patients and [81%] had seen a significant reduction in their disability.

So this most recent resultant data is clearly not reflective of the aforementioned 30% number.

But let us also not confuse syntax with semantics here. . . . . I'm not saying that HSCT stops the disease in all treated patients (includes progressive population). What I've found is that "for all those people that do have their MS disease halted via HSCT, they have yet to relapse or continue active MS progression since."

As for CV's important question of why the nonmyeloablative regimen is effective if it doesn't completely wipe out the offending lymphocytes? This is the magic question that I think no one knows the complete answer (yet). Clearly the non-myeloablative protocol is very immune-suppressive, although not so much as the myeloablative protocol that wipes out nearly 100% of offending lymphocytes. Probably the non-myeloablative HSCT protocol ablates or degrades "just enough" of the immune system to be effective at stopping MS. The non-myeloablative protocol is clearly a balance between eliminating autoreactive immune cells (that cause MS) and retaining just enough memory cells to obviate the need to re-vaccinate. This also (as opposed to the myeloablative protocol) makes it a more difficult protocol to administer because the delivered chemo dosages are extremely critical and very different for each individual because its based strictly upon body weight. A little too much chemo could be dangerous (causing lymphoproliferative disorder), and too little chemo could be ineffective to stop MS.

The myeloabltive protocol chemical administration has a wider dosage variation tolerance because it's a binary function that eliminates the immune system in it's entirety. I'm sorry to repeat what I have already posted before but at this point it is only theory on the subject. . . .

Following my own research comparing the two different HSCT treatment protocols I arrived at my own decision to seek the myeloablative (BEAM) therapy for one specific reason that is just my own thinking that can clearly be characterized as conjecture since I have no proof or evidence that I am correct in my logic here. . . . the surrogate indication of re-vaccination requirement following myeloablative (BEAM) therapy tells me that the immune system is definitively & completely rendered antigen naive and I think has a better possibility of remaining self-tolerant (and MS progression-free) for a longer period of time as opposed to the non-myeloablative protocol that does not render the body's immune system entirely antigen-naive. So far (at 8 years post-transplantation) the clinical results indicate that both approaches have shown substantially similar curative therapeutic benefit. But the question now is "what happens over a longer timeframe, such as 15 or 20 years?" Will the two approaches still have comparable curative efficacy? No one yet knows the answer because we have not yet hit this milestone. But since I was more interested in a durable long-lasting cure as opposed to a more rapid recovery timeframe, I chose the myeloablative (BEAM) protocol in the chance that it "might" have better lifetime curative success. Of course only time will tell on this since there is no way to know the answer today. I may end up eating my own words at some point in the future if my assumption is proven incorrect. On the other hand, if my assumption is proven correct I'm going to be extremely happy that I chose the myeloablative protocol. Eventually we'll see which way this proves out. But if you have MS and are looking to complete an HSCT procedure, you can consider these factors as part of your criteria and decide for yourself.

I got the numbers from a combination from the phase 1 trials and several people I have talked to who went through the trial and told me their release stated a 5% rate was the rate that people had to agree to to go further in the trial. Anecdotal evidence from people who had the hsct procedure and told me of their experience should be vital to folks who, like me, take those things into consideration. It wont deter me, but folks researching the issue should know the risks. I think folks like you and asher should be commended, and thank you, but folks need to know the potential risks to go along with their cost benefit analysis.

_________________
"A gun is a tool, Marian; no better or no worse than any other tool: an axe, a shovel or anything. A gun is as good or as bad as the man using it. Remember that." -- Shane

Who is John Galt?

Yes, I agree that in the phase I trial protocols the mortality rate was probably assesed correctly at 5%. The reason is because the phase I trials included Total Body Irradiation (TBI) that was responsible for the the early mortality and main complication side effects. TBI is nasty. The good news is that TBI is no longer used in the current MS treatment protocols because it has been found to not add to the curative results, only adding unessesary risk.

The great news is that today's current chemical-only HSCT protocols are much safer, less risky and gentler than the early study protocols that included TBI. But today's protocols fortunately still maintain very good curative efficacy.