2 Years Post HSCT And MS Still Stopped

[KMG]

George you are 100% correct that the latest published study from Dr. Burt has all 21 MS patients free of progression with a follow up period between 24-48 months. There were 5 (24%) that relapsed but responded very well to further immunosuppression and were still progression free.

My comment yesterday regarding my conversation with Dr. Burt was completely anecdotal but close to the findings of the previous study. What I should have included in my comment is those that relapsed responded better to additional immusuppressive treatments, remain progression free and most experience significant reversal of symptoms like our dear friend George.

Thanks for all you do for us!

Kevin
(KMG)

[HUD45]

Hi KMG, I was wondering if you could explain a little further what "further immunosupression" means. More MS drugs or another chemo procedure or what? Just curious..HUD

[georgegoss]

George you are 100% correct that the latest published study from Dr. Burt has all 21 MS patients free of progression with a follow up period between 24-48 months. There were 5 (24%) that relapsed but responded very well to further immunosuppression and were still progression free.

My comment yesterday regarding my conversation with Dr. Burt was completely anecdotal but close to the findings of the previous study. What I should have included in my comment is those that relapsed responded better to additional immusuppressive treatments, remain progression free and most experience significant reversal of symptoms like our dear friend George.

Thanks for all you do for us!

Kevin
(KMG)

This is actually quite interesting. Sincerely thanks for sharing this, Kevin.

I also would be interested to know more regarding what Hud has brought up regarding additional treatment. I'm sure there must be some report (or something) about this. At the least, I bet Dr. Burt should be able to answer.

[shaight]

Dr. Burt has all 21 MS patients free of progression with a follow up period between 24-48 months.

how good is that! it's nice to hear about other people beyond George benefiting from this treatment. it would be really nice to see any one of these 21 posting on this board.

with that said, i really appreciate George posting and teaching me as much as you do. thanks!

[shucks]

Between advice from George, Asher, packo, Dave at active msers, and some folks over at Patients like me, I have had a chance to personally correspond with 8 or so people who have had the procedure outside of forums. Other than Stella, Everyone I have spoken to has had similar results. I also talked to several folks who underwent the procedure for ALS, and it didnt work for any of them.

[georgegoss]

Dr. Burt has all 21 MS patients free of progression with a follow up period between 24-48 months.

how good is that! it's nice to hear about other people beyond George benefiting from this treatment. it would be really nice to see any one of these 21 posting on this board.

with that said, i really appreciate George posting and teaching me as much as you do. thanks!

Good idea, Shaight! These are the only people that I am personally aware of from the initial 21 people from in the phase II non-myeloablative HSCT trial with Dr. Burt.

(Barry Goudy is a friend of Lisa Curtis so you can contact him through Lisa listed below)
(Edwin McClure) http://www.cbsnews.com/stories/2009/02/ ... ncol;lst;1
(Brian Tilaro) http://allyoumed.com/
(Sandi Selvi) http://www.sandiselvi.com/
(Bethany Papilardo - watch through the first patient with Lupus cured with a stem cell transplant to watch the second segment of Bethany):

Although not part of the phase II trial, and not part of the 21, these people received the exact same HSCT treatment protocol from Dr. Burt. Good personal stories:

(Marc Coppins - part of the current phase III study work) http://www.marcstemcell.com/
(Lisa Curtis) http://lisashope.com/
(Heidi Strauss went to Israel to have the same non-myeloablative procedure with Prof. Shimon Slavin that previously collaborated with Dr. Burt) http://www.caringbridge.org/visit/heidistrauss/mystory

And then there are also many people that have received the myeloablative HSCT (same or similar as performed in the HALT trial by Dr. Richard Nash at the Fred Hutchinson Cancer Research Center in Seattle). These are just a few as I'm sure there are probably many more to be found out there:

(Carmel Turner) http://msstemcell.com/Home.php
(Dave Bexfield) http://activemsers.wssnoc.net/forumdisplay.php?f=6
(Cris McGuey - A unique myeloabltive protocol administered in Ottowa by Dr. Mark Freedman) http://my-end-to-ms.blogspot.com/
(Hanna Vesterager in Norway) http://hannastamceller.blogg.no/blogg.html
(Asher Cohen) http://themscure.blogspot.com/2011/06/p ... cohen.html
(George Goss) http://themscure.blogspot.com/2010/06/s ... rence.html

[shucks]

Thanks for consolidating all of that info george. I have exchanged emails with a fair amount of those guys, and most were hugely helpful in making my decision to follow up on this treatment.

[shucks]

http://www.bbmt.org/article/S1083-8791(11%2900498-8/abstract


George, Have you read this yet? I haven't bought it, but the abstract seems like it would be of import to the folks around here.

Shucks

[georgegoss]

http://www.bbmt.org/article/S1083-8791(11%2900498-8/abstract


George, Have you read this yet? I haven't bought it, but the abstract seems like it would be of import to the folks around here.

Shucks

Sorry for my delayed response, Shucks. And thanks for the article abstract link. I went online and purchased the article to read. Authored primarily by Dr. Muraro, he outlines good points. The main takeaway is that HSCT as a treatment for MS (and other hematologically-rooted autoimmune diseases) is clearly gaining traction and momentum. Before now there was no specific criteria for which the broader medical establishment would consider the use of HSCT for MS. But in this recent (Jan, 2012) publication he outlines a narrow definition (agressive evolution/progressive inflammatory MS) that should become a standard treatment option, although it does not (yet) specifically advocate for a broader use of HSCT for a wider range of MS cases (even though HSCT clearly offers curative benefit for the majority of MS patients, regardless of disease status).

To me, this article is confirmation that the medical community is slowly opening their eyes to the fact that HSCT works so well for MS that eventually the broader medical establishment will have (or be forced) to accept HSCT as a "standard" theraputic approach for a larger percentage of the MS community, lest they will be run over by the HSCT truck coming down the road if they don't already see it coming.

So although Dr. Muraro is somewhat conservative in his suggestion to consider HSCT for a narrow subset of the MS population (he has to advocate a conservative position to maintain his credibility in the medical community), I can see where this is going. . . certain eventual full acceptance of HSCT by the medical community. Especially after HSCT is approved by the FDA as a standard treatment for MS sometime just after 2020. The message to doctors is clear. . . . get with the program to understand and accept HSCT as a valid treatment option for MS, or risk getting slapped in the face and becoming irrelevant in your own field (especially neurologists!).

As of today each time I speak with a person seeking HSCT for their own MS (so far a dozen already treated and another dozen lined up to do so), they tell me that their doctor doesn't support it. No surprise here. But that WILL eventually change. Even if the doctors have to be dragged kicking and screaming. I always ask the people seeking HSCT to ask their doctor to read the following page, just in case there is a small chance they might have a modicum of objectivity:

http://themscure.blogspot.com/2010/06/s ... rence.html

- George

[jabberwock]

Hi, I am posting my first board message here because, after reading much of the material over the past several months, I believe that HSCT is potentially the best, and possibly only, option for my sister.

My sister was diagnosed with PPMS in 2007, after experiencing progressive weakness in her right leg. In the years following her diagnosis, the weakness has left her with severe dropfoot and an uneven gait with increased instability when walking. She still walks unaided, although her "wallwalking" has increased and she will finally accept an offered arm for support when walking on uneven ground. She has experienced no other symptoms of MS. I even manage to convince myself sometimes that she does not have MS, but the doctors could come up with nothing else as an explanation, and did find lesions (I think mostly on the spine) in her MRIs. If she was ever advised of her EDSS score, she does not remember, but I would put it around 4 at this time.

I am encouraged by the success of George and Asher and others on this site, and am particularly interested in hearing more about HUD's progress since he has PPMS. I am aware that the success rate for patients with PPMS is not as good as for those with RRMS, and that any improvement experienced after the procedure is not as dramatic. There even appears to be some speculation that the autoimmune system is not as involved in PPMS as it is in RRMS. My biggest concern is that PPMS is a completely different animal and HSCT would not have any impact on it at all.

At this point in time, my sister would be happy if HSCT would simply stop the progression of her disease. Perhaps in time, MSC therapy, or some other process will be able to repair the damage which has already occurred, but we do not really expect any improvement to result from HSCT. We just want to stop it from getting any worse!!

We are fortunate to live in Canada and I have asked my sister to set up an appointment with her neurologist here in Toronto to get an updated MRI and EDSS assessment, and ask for a referral to Dr. Mark Freedman in Ottawa to see if he would consider her for HSCT. Her age may be against her (she is 57), but she is otherwise healthy, and if her EDSS is scored at less than 6, maybe he would be willing to try it.

George, it appeared to me that the chart on your website gave results only for PPMS patients with an EDSS greater than 6. Is there any data available for the success of HSCT on PPMS patients with an EDSS less than 6? Do you believe this could be a good option for my sister?

I would appreciate any insight you may have.

Bonnie

[HUD45]

Hi Bonnie. Good to hear you are doing your homework to help your sister.

I am coming up on my 6 month date from my HSCT. I uuderwent a non-myeloblative protocol. I am still experiencing periodic worsening of fatigue symptoms and perhaps more disappointing gradual weakening of my legs. The good news is that time is still on my side. The next 6 months should define weather or not I can call the treatment a success. Pre treatment, I would have been really happy with a halting of progression of my PPMS but I have not seen that so far. I am hoping even for a slowing of progression now.

I agree and the literature also agrees with you that PPMS is harder to treat than RRMS and even SPMS. You may be correct that the immune system involvement is different between the two diagnoses, and there is a ton that could be said about this. I fully understand that the success rate goes down for PPMS cases treated with HSCT.

That being said I am really glad I had the treatment and am still very hopeful of a successful outcome in the next year.

I have spoken to Prof. slavin at length about MSC infusions. He seems so very positive about the future potential applications for their use. He explained that the research in animal studies shows incredible advances in neuronal and myelin regeneration. He does admit that it is difficult to predict benefit case by case though because it is such a new discovery. He also presented some interesting anecdotal sucess cases...Even with PPMS. As for me, I am waiting for hopefully a halting of my MS progression before further consideration of MSC infusion.

Here is how it works for MSC at CTCI...First bone marrow aspiration under anesthesia from hip done in Israel. Then you go home and wait while they do a 3 month colony expansion procedure followed by reinfusion in Montreux Switzerland..Probably a 2- 3 night stay. Approx cost 32,000 usd (as of 6 months ago).

I hope this helps...Let me be clear... I am very hopeful of a positive post HSCT outcome and will keep you posted on tims...HUD

[CVfactor]

jabberwock,

I believe that the myeloblative protocol has a better success rate at halting MS compared to the non-myeloblative protocol for PPMS. I thought I read that it is around 70% success rate. You can check out Georges blog and find a lot of information there.

[georgegoss]

Hi Bonnie,

First of all my empathy for you and your sister. No one should have to endure the stress of having to deal with MS. I hope someday the world will be ridded (prevented) of this meanace.

Very sorry for my long-winded response. I'm still trying to get the nerd out of my head. He's not gone yet.

Also I'm glad Hud had a chance to add his comments. His specific MS case type (ambulatory PPMS with EDSS <6.0) is unusual in the sense that this is not a well-studied area for determining curative results of HSCT. His feedback regarding this is valuable information.

A little history. . . . all the early HSCT studies were performed on advanced MS cases with people that were generally not ambulatory. Nearly the entire population of this group were either PPMS or SPMS in the EDSS 6.0 - 8.0 range because it was thought at that time to perform HSCT on the most severely disabled patients. So the curative statistics are well understood for this group, which I list below.

But also in these early years there was one rapidly-evolving severely disabled RRMS patient (EDSS 8.0) in this group of treated patients that also underwent HSCT for his MS. And low-and-behold this patient eventually recovered to en EDSS of approximately 2.0 - 3.0 range. This almost fantasically unbeleivable anomolous result shocked the researchers and is what finally made them realize that HSCT can work more effectively on early relapsing cases. It has in fact been seen that three things "generally" indicate more favorable outcome. . . . 1) Relapsing (inflammatory) disease status, 2) Shorter duration of time from initial diagnosis, and 3) Ambulatory with EDSS <6.0. Having even one or two out of these three also bodes better for progressive (SP, PP) patients.

Here are the statistics of all the patient grouping populations:

For early RRMS cases
Stopping of underlying MS disease activity in virtually 100% of all patients
"Substantial" improvement/reversal of pre-existing symptoms

For later RRMS cases with EDSS >6.0
Excellent probability of stopping disease activity (my own guess is in 95% - 99% of the population)
"Substantial" improvement/reversal of pre-existing symptoms also likely for this population

For advanced SPMS cases with EDSS >6.0
Stopping of underlying MS disease activity in 78% of patients
Improvement/reversal of pre-existing MS symptoms range from none-to-moderate (impossible to predict) based on current data

For early SPMS cases (EDSS <6.0) [my case]
This not a widely studied area, but there is some data that indicates approximately 85-95% will have their MS stopped and are "likely" to experience none-to-substantial improvement/reversal of pre-existing symptoms, athough this magnitude of improvement is unpredicatable

For advanced PPMS cases (EDSS >6.0)
Stopping of underlying MS disease activity in 66% of patients
Improvement/reversal of pre-existing MS symptoms unlikely, but also not impossible.

For earlier PPMS cases (EDSS <6.0)
This is the most unstudied and not quantified population result that only has anecdotal patient outcomes.
There is early indication that PPMS patients with an EDSS <6.0 will do better both in terms of stopping of disease (I would expect a probability of better 66%) and potential improvement of disability. But there simply is no population data to make an accurate probability prediction. Certainly I would expect the statistics to be better for this group as opposed to the advanced PPMS cases, but can't say precisely what that is.

When taking into account PPMS patient types, the picture is not wholly complete. However, the main takeaway lessons from this data are 1) Treatment earlier in the disease lifecycle with lower EDSS is better, and 2) "Most" (but not all) patients will see a beneficial result (stopping of underlying disease activity and possible symptomatic improvement) regardless of the type of disease they have, although this is less than 100% of all people treated.

Cutting to the present day. . . . the researchers running the clinical trials (such as Dr. Burt in Chicago and Dr. Nash in Seattle) have made the decision to limit treated patients to early RRMS / rapidly evolving patients because HSCT works "best" on such patients, not because the treatment cannot have beneficial effects for progressive patients as well. Basically, by limiting the patient inclusion criteria as they have, they get to look like medical superstars letting people get out of their wheelchairs. This is how they will acheive fame and glory. I don't know exactly what their personal motivations are.

I took the limited data points from all the trials over time and created an interpolated graph on this page that attempts to correlate HSCT efficacy with MS disease type (which clearly indicates that "most" MS patients benefit from HSCT, regardless of disease type):

http://themscure.blogspot.com/2010/06/s ... rence.html

Going to the situation with your sister. . . . . . Of course there are no gaurantees in life, just probabilities. But I think it not reckless to make some general statements regarding your sister having reasonably good odds of beneficial effect from HSCT because of these factors that you describe of her status:

1) Relatively recent (2007) diagnosis
2) Ambulatory (EDSS <6.0)

So when you state "I believe that HSCT is potentially the best, and possibly only, option for my sister," I would agree with you for the simple fact that, although there is no gaurantee your sister would arrest her MS via HSCT, certainly she has far better-than-even odds of doing so. For myself, if I were in the same situation as you have described, likely I would seek HSCT.

I am really hoping that Hud will eventually be able to affirmatively report his underlying PPMS disease activity as stopped. At least the odds are also in his favor. He has given his disease a great shot across the chops and I applaud him for that!

Just to share one additional anecedotal case. . . . I started comminucating last year with a man from Seattle who's wife has PPMS (diagnosed 2002, EDSS 6.0). He also read my blog and we talked about her case and they decided to seek a myeloablative HSCT protocol (identical to my own) in Bangalore, India. For the approximate timeframe of two years prior to her HSCT she went from an EDSS 2.0 to 6.0. Clearly a very rapid deterioration (which is probably why they decided so expeditiously to seek a serious treatment like HSCT). Long story short, I spoke with him yesterday and his wife is currently four-and-a-half months post-transplant and still recovering. It is still early in her recovery and I would not expect to notice any specific benefit until at least the 6-12 month timeframe. But interestingly she claims to be convinced that her disease is now stopped (no further physical deterioration). Additionally, she says that she is no longer sensitive to heat (this was also my first symptom to dissappear immediately following my own HSCT so I actually beleive this is likely real and bodes well for her disease being stopped), and she claims that she has regained balance/coordination and speech impairment, although she is still working on physical therapy of her quite weak legs. From her report, it sounds like she may have "possibly" already seen some early indication that her underlying disease activity has been halted. Another six months should indicate for sure which side of the cure curve she has come down on. But so far so good with no bad news as of yet.

The point here is that individual cases cannot and do not specifically translate to anyone else. Only a population study can tell us for sure what the probability of outcome will be. But even then, predicting an individual's outcome is impossible. I would imagine that over time more MS'ers in this ambulatory PPMS population will receive HSCT treatment and that will slowly build up a better picture of what result is likely to occur. Until then, I hope to see more people fight their disease!

[georgegoss]

Hi KMG, I was wondering if you could explain a little further what "further immunosupression" means. More MS drugs or another chemo procedure or what? Just curious..HUD

Hi Hud,

I found out the answer as this is all becoming clearer to me over time. . . . because the non-myeloablative HSCT protocol walks a fine line between too little immunoablation (won't stop the MS) and too much immunoablation (causing dangerous lymphoproliferative disorder), the infused chemical cocktail dosage to the body must be extremely carefully controlled (by body weight), and therefore they sometimes come down on the side of slightly less chemical density (for patient treatment safety). So it makes sense that there would be a possibility that a few patients would relapse. So to get the patient back into remission post-transplantation they infuse additional doses of cyclophosphamide which has the effect of clearing out more lymphocytes that they didn't get with the main procedure.

This is an interesting contrast to the myeloablative protocol which is not so sensitive to drug dosing (although the dose is still important). The BEAM therapy is basically a binary treatment in which nearly the entire lymphocyte population of the body is eliminated (which is also why it is considered more aggressive) and post-transplantation relapses are fewer (if at all). As opposed to the myeloablative protocol, the non-myeloablative HSCT treatment doesn't eliminate all the lymphocytes of the body. It just reduces the total population, as described by Dr. Burt. . . .

[For the non-myeloablative HSCT protocol for MS] "Autoreactive memory cells survive and autoantibodies, while significantly diminished, generally remain positive."

This is also why the myeloablative (BEAM) protocol requires re-vaccination and the non-myeloablative does not. Basically, the non-myeloablative HSCT protocol is actually more complex and harder for the doctors to administer compared with the myeloablative protocol. Also why there are few facilities around the world that will perform the procedure.

Regards,

George

[CVfactor]

I think the myeloablative protocol fits in completely with what the immunologists believe what causes MS as well as other autoimmune diseases. It is a loss of self tolerance. Your immune system has developed in such a way due to genetic and environmental factors to no longer be able to distinguish self from non-self.

Re-setting the immune system means just that, you have to erase all of the memory components involved. The only question I would be concerned with this procedure is that it has to be done at an experienced and reputable institution.