CVfactor wrote:Also, it seems like your immune system health at the time of challenge would be a key factor. For example it has been shown that low vitamin D levels during childhood is likely a risk factor for MS. So I would definetely want to have a healthy Vitamin D level after HSCT. So as you said before George you would have to have the same combination to the MS lock to re-acquire the disease. I think the odds would be very low, but time will tell.
georgegoss wrote:HUD45 wrote: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
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.
CVfactor wrote:If they are doing this in a trial setting it seems like it would negate the trial. It would be akin to changing the dosage in the middle of a drug trial to effect the outcome.
packo wrote:I am not an expert, but if I would have to apply both myeloablative and non-myeloablative protocols on a various group of individuals, I would go with the myeloablative on those patients with a) RRMS, especially those with very active (inflammatory) disease and low EDSS score and b) those individuals with aggressive disease who accumulated lots of disability in a very short period, and non-myeloablative for everybody else, mostly patients with SPMS and PPMS, but this is just my opinion, call it a hunch based on my understanding of the disease. Opinions?
shucks wrote:I had a chance to discuss the issue with dr Burt a month or so ago. He told me that the goal was to come up with a specific treatment that would stop the disease course without undue toxicity. He believes they lympho ablative to be just that. He was very matter of fact about it.
CVfactor wrote:Personally, I am going to try Copaxone first to see if I am a lucky one who it works on. If this fails and I continue to progress I will work on getting funds for a BEAM procedure.
If I had PPMS I would try to get BEAM as soon as possible because there really are no other alternatives. I guess in my view I don't really understand the theory of the non-myoablative procedure. If I was going to undergo HSCT I would only want to do it once.
georgegoss wrote:packo wrote:I am not an expert, but if I would have to apply both myeloablative and non-myeloablative protocols on a various group of individuals, I would go with the myeloablative on those patients with a) RRMS, especially those with very active (inflammatory) disease and low EDSS score and b) those individuals with aggressive disease who accumulated lots of disability in a very short period, and non-myeloablative for everybody else, mostly patients with SPMS and PPMS, but this is just my opinion, call it a hunch based on my understanding of the disease. Opinions?
Hey Packo. . . I can see your thinking here. Also makes sense and I wouldn't argue against it. Just one thought regarding progressive cases. . . how can one determine an "agressive" PPMS case? I suppose that could only be detrermined by the rate of diasability and EDSS deterioration? Would you also support a myeloablative protocol for a rapid agressive PPMS disease as well an RRMS one? Or only reserve it for aggressive RRMS? I could easily see the logic cutting both ways. But like you, I also have no hard data to back up my thinking here.
The only thing I know for certain is that, as opposed to the non-myeloablative protocol, for the myeloablative protocol there are few remaining reactive lymphocytes and autoantibodies following treatment. But of course, I don't know what that would directly impact. Other than only guessing as to what's going on at the cellular level, the only way to measure protocol efficacy vs. disease morphology is (like you've already said) to randomize these groups to either of the two protocols and then measure EDSS over time. A good idea but I'm thinking this won't happen for a long time to come. Perhaps the next step of the clinical trial work after HSCT becomes FDA-approved? Maybe there's still time for us to earn our medical degrees and then you and I can run the trial!
CVfactor wrote:For the non-myeoblative procedure, what is the recovery like? I know that with the myeoblative it is very critical to maintain sanitary conditions since you basically have no immune system after the procedure.
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