This Is MS Multiple Sclerosis Knowledge & Support Community

shaight wrote:ya! nice George! congrats to you and your wife. with a name like Kai you have to get him surfing right away!

Excellent! I also heard that Kai is both a common Norwegian and Finnish name, as well as a Hebrew name. All unintended from our side. We just wanted to find a male name that was both 100% American English and 100% Japanese (my wife is Japanese). Kai fits the bill. The Japanese name means "Ocean."

Congratulations George!!!

congrats to the whole Goss family....Yuko can finally join you in a fine, celebratory Merlot!

brad in sarasota

OK, just to throw some fuel on the fire (after this forum really prompted my in-depth thinking about this subject matter; thanks everyone!), I added some comments to my HSCT treatment options page as follows. . . .

http://themscure.blogspot.com/2011/06/g ... -have.html

[The following comments are added at +2 years post transplantation following my ability to better complete my scientific understanding of the treatment & outcome data of the two different HSCT protocols for MS and is a copy of a message that I recently sent to a friend that had HSCT for his own MS]:

I have only one "potentially" serious (not yet definite) concern with the non-myeloablative HSCT protocol as administered by Dr. Burt and Prof. Slavin. . . . Its a good treatment that has been definitively shown to be effective in the treatment of MS. But because the non-myeloablative HSCT protocol does not completely ablate the entire compliment of in-vivo lymphocytes, "sometimes" (a small minority of cases) treated patients with RRMS have a MS-relapse following treatment which is then quickly put into remission with additional doses of cyclophosphamide infusions post-HSCT. (This "relapse" phenomenon has not been shown to happen with the myeloablative (BEAM) HSCT protocol that wipes out essentially the entire population of the body's lyphocytes; leaving little or no chance of surviving autoreactive lymphocytes that cause MS disease progression.) A little bit this subject matter troubles me because it seems to indicate that for an isolated few treatment cases the non-myeloablative protocol may be "too gentle" and insufficient to wipe out the necessary fraction of the autoreactive lymphocyte population in these few number of people that results in failure to completely stop the progression of the underlying MS disease activity and allows some forward disease progression (although it is probably at least slowed down). If this happens in an RRMS patient, then it should be easy to identify because the patient will manifest an isolated identifiable relapse episode that should be easy to temporally-spot and treat. However, what happens in isolated progressive (SP or PP) patients in which the MS is not completely stopped by the non-myeloablative therapy? This is a completely unstudied area and creates some concern for me that there could be some progressive patients (PP or SP) that do not have "halted" MS disease activity in using the non-myeloablative HSCT protocol. If such cases do exist, then it would seem logical to me that they would also likely benefit from cyclophosphamide re-treatment. But how to identify such "failed" progressive patients? This would seem to be much more difficult to determine because SP and PP MS'ers don't have isolated relapse activity, just further progression and accumulation of MS-induced disability that does not remit. So the question for me is manifold. . . . . how to define an insufficient stopping of progressive disease activity following non-myeloablative HSCT? And if it is determined to be the case, when and how to re-treat with cyclophosphamide to arrest underlying residual disease activity?

I'm just now coming to my own recent conclusion that it 'might' be (this is a definite maybe) preferable for progressive patients to favor a fully myeloablative (BEAM) protocol to avoid the potential possibility of being in the small group of non-myeloablative-treated HSCT patients that experience further progression and avoid being accidentally caught in such a difficult-to-diagnose / identify situation. But no need to panic reading my words as this is all just pure conjecture on my part. I have no direct evidence this is going to be a problem. I still strongly favor non-myeloablative HSCT over no HSCT treatment at all for all MS patients. So if it were me with a progressive disease status and I had to choose between a non-myeloablative HSCT procedure (Dr. Burt at NWU in Chicago or Prof. Slain at CTCI in Israel) or no treatment at all, definitely I would absolutely go for the non-myeloablative treatment without hesitation. But on the other hand, as a progressive MS'er (I was) and had the option (I did) of seeking a myeloablative or non-myeloablative HSCT protocol I would choose the myeloablative protocol, if available to me (it was and I did).

So here is my current updated thinking based upon my understanding of the differences in "potential" HSCT protocol outcomes. . . . "If it were my own respective MS disease status". . . . I would favor the myeloablative (BEAM) HSCT protocol for progressive (SPMS, PPMS) cases. and either of the HSCT protocols for relapsing cases of MS. However, with no other option, I would be totally OK with receiving the non-myeloablative HSCT protocol for my progressive MS since it would still be a superior-probability option to potentially stop my MS as opposed to all other current pharmacological therapeutic treatment approaches.

georgegoss wrote: "sometimes" (a small minority of cases) treated patients with RRMS have a MS-relapse following treatment which is then quickly put into remission with additional doses of cyclophosphamide infusions post-HSCT.

George, I'm curious about this relapse. Does it always happen immediately after the HSCT treatment or do they monitor the patient over a long period of time and then give more cyclophosphamide when the patient relapses some time in the future?

I guess one indication if it did not work on a person with SPMS is that if you did not have any improvements over time as you and Asher seem to be experiencing.

But, I have been doing a lot of research on the causes of MS and the different phases of disease. One new theory is that during the relapsing phase, the meylin sheath is targeted. The sheath can be damaged but remeylination can occur.

Durring the secondary progressive phase of the disease the theory is that when the meylin sheath is damaged beyond repair, the axon is exposed and thus permanent damage can begin to occur to the axon.

Demyelination alone does not appear to cause axonal injury, and most axons survive transitory demyelination. However, axons that are chronically demyelinated are at substantial risk of degeneration. This may reflect the loss of important nerve growth factors that are produced by surrounding oligodendrocytes and that are essential for axonal survival.

http://www.jhasin.com/files/articlefile ... p37_41.pdf

I'm not sure this also holds true for primary progressive MS because this seems to cause axonal loss at the onset, similiar to ADEM but maybe not as aggresively. However, I believe the theory for secondary progressive MS as described above could explain why there is a better succes rate with HSCT the sooner it is administered.

What i was told was that a relapse usually occurs in those that get the "fever that no one can explain" during the Lympho ablative. That is just what I take from my meeting with NWM.

So is this relapse confirmed by changes in an MRI or is it subjective?

Thanks Shucks. That's very interesting feedback regarding Burt's program. Still somewhat mysterious, but interesting nonetheless. Perhaps related. . . . 90% of the fully myeloablative (BEAM) protocol patients develop a common idiopathic (cause unknown) fever during treatment (just as I did). But most of the patients (none reported to date) have relapses requiring retreatment with additional drugs. But of course the myeloabltive HSCT protocol is not identical to what Burt is doing. So perhaps more time and patient experiences will help better elucidate this topic.

And thanks for the comments CV. . . . Based on the data I saw it looks like a MS-related relapse can occur anytime following non-myeloablative HSCT and has a random-like time distribution (although there 'seems' to be a bias toward a timeframe closer to just after the HSCT treatment which will eventually be better time-definied with greater treatment population statistics). So watching the treatment population over a longer period of time would seem important, which they continue to do with the phase III-treated patients.

And I enoy reading all your statements regarding what is going on with nerve damage in progressive patients as to why does RRMS most often eventually transition into SPMS with axonal dystrophy dominating over demyelination (you may be correct on all fronts). . . . . still an unexplained phenomenon and a mystery as to why it happens. I bet the underlying detailed explanation for this will likely be answered at the same time the fundamental cause of MS is found. Hopefully we won't have to wait too long for this.

CVfactor wrote:So is this relapse confirmed by changes in an MRI or is it subjective?

Although they do monitor post-HSCT patients with MRI, such imagining is not nearly as useful as many people beleive because MRI images have a weak coorelation (at best) with actual clinical disability. Generally MRI's can only indicate if there is "active" disease progression occuring, which is more qualitative as opposed to quantitative. So diagnosis and identification of relapses is based upon reported clinical manifestation(s) and measure of EDSS, which is objective without need for MRI scans that are often subjective themselves (since MRI's have to be read and reported by a human being which is tantamount to second-hand information).

I would argue that a clinical relapse could be very subjective especially after a relatively aggresive treatment like HSCT.

Just look at the miraculous improvements seen by people who underwent Liberation treatment, so I think it works both ways.

Changes in MRI are crucial for identifying a relapse based on dissemination in space and time at least for RRMS.

But I would say that the only way to really know how effective the non-myeoblative method is would be to not allow re-treatmant (same as a drug trial), but in the end this would be considered cruel.

CVfactor wrote: But I would say that the only way to really know how effective the non-myeoblative method is would be to not allow re-treatmant (same as a drug trial), but in the end this would be considered cruel.

Indeed. Agreed.

CVfactor wrote:Just look at the miraculous improvements seen by people who underwent Liberation treatment, so I think it works both ways.

Changes in MRI are crucial for identifying a relapse based on dissemination in space and time at least for RRMS.

I can say this here because I'm sure the majority of people in this forum have a scientific mindset. . . . I'm certain in my own mind that any improvement seen following CCSVI treatment is just a placebo effect. True, it is real. But it's not a cure becaause it is not lasting or durable, as is the case with HSCT.

The biggest problem with MRI's is that they are not strongly correlated. Some people are "sub-clinical," in that they have strong lesion loading under MRI imaging but have no clinically-evident symptoms of MS. And then at the other end of the spectrum some people are "hyper-clinical" in which people have very severe clinical menifestations and symptoms of MS but absolutely no detectable MRI lesions activity. It's difficult to rely soley on a measurement method that sometimes produces such a result. Too unreliable. Certainly at least for treatment decisions.

My doctors describe my lesions as vey subtle, yet I am an EDSS of 8. The nature of PPMS I guess.

Hi Kate,

Wow. EDSS 8.0. I only personally know one person with such an advanced progressive status. It really unfairly robbed him of many of the ordinary enjoyable things in life. My heart goes out to you and your family. I wish the science supported some form of treatment for such an advanced progressive case that would result in substantial improvement. You have a good point in that the enigma of PPMS is somewhat baffling as to why and how people develop it from the start. Some more seriously than others.

This is my friend. At least his mind and will are still strong. And I find it amazing and admire that he can occasionally still overcome his disability. . . . .

http://themscure.blogspot.com/2011/06/jacks-jump.html

My best regards to you.

George

Following upn my previous comments regarding how 'sometimes' the non-myeloablatibe HSCT protocol requires some form of re-trateatment as ccompared to the (BEAM) myeloablative HSCT therapy that seems to not ever require re-treatment (because it more-completely ablates a higher proportion of the in-vivo lymphocyte population), here is the most recent posting from Lisa Vargas-Curtis that had Burt's non-lymphoablative HSCT protocol (which is further reason why I favor the fully myeloablative HSCT protocol for progressive MS cases).

I'm confident that following her retreatment, she will finally be ridded of MS. Just too bad it wasn't accomplished the first time:

http://lisashope.com/blog/

Then we met with Doctor Burt.

They found a new enhancing lesion in the frontal lobe of my brain. Yeah…
I know you are all thinking what I was that day….WHAT!!!! I went through all of this and the disease is still hanging on!!!! I’m, as I would say in front of my kids, VERY ANGRY!!! Needless to say, this took a few moments to sink in. But, thankfully, I was sitting there with my husband, who seems to really know a lot of stuff and he discussed with Dr. Burt about what to do next to finally kick the MS out. The answer…

More chemo.

So, it was decided at my one year evaluation that I would get one Cytoxen IV a month for six more months and this would finally give the MS one final aggressive kick that it needed to go away. Apparently this has happened only a handful of times before and with further immunosuppression, the disease says buh bye. I don’t mind doing this and am remaining hopeful that in the end, I will come out ahead. I also wanted to say that the other tests that they evaluate my abilities on went pretty good for the most part. The peg test was done right after I found out about my new lesion and was a complete failure. I did have a lot on my mind while trying to put those little round pegs into the little round holes after all. But, after talking a little bit with Kim, the nurse; I was able to walk faster for the 25 foot timed walking test without using my cane and did better with the wonderful math test they gave me. Both of these tests showed an improvement compared to the 6 month results.