Stem cell patient's path to recovery

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Stem cell patient's path to recovery

Postby scorpion » Fri Feb 11, 2011 12:56 pm

I am generally not one to post feel good stories but I thought this was interesting:

"In 70 per cent of patients there is no evidence of recurrence of the disease over 100 months, but what happens beyond that, we don't yet know," he said.


Would love to know how they came up with those numbers because they sound pretty damn good. Please skeptical side leave me be!!!

http://www.adelaidenow.com.au/stem-cell ... 6004747802
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Re: Stem cell patient's path to recovery

Postby Lyon » Fri Feb 11, 2011 1:19 pm

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misleading article?

Postby hwebb » Fri Feb 11, 2011 3:09 pm

this story was splashed across the Australian papers today. I am very happy this person has experienced such a dramatic positive result...but the article has some misleading points. The patient states they are "cured" of MS on several occassions, but also indicates they haven't had a follow up MRI yet...so they dont know the effect on their lesions (err...how could MS be cured if there are still multiple lesions?).

The most important thing is that the patient has an improved quality fo life.
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Re: misleading article?

Postby Lyon » Fri Feb 11, 2011 4:11 pm

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Re: misleading article?

Postby scorpion » Fri Feb 11, 2011 4:20 pm

hwebb wrote:this story was splashed across the Australian papers today. I am very happy this person has experienced such a dramatic positive result...but the article has some misleading points. The patient states they are "cured" of MS on several occassions, but also indicates they haven't had a follow up MRI yet...so they dont know the effect on their lesions (err...how could MS be cured if there are still multiple lesions?).

The most important thing is that the patient has an improved quality fo life.


Thanks for reading the article carefully and pointing this out.
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Re: misleading article?

Postby CuriousRobot » Fri Feb 11, 2011 8:58 pm

hwebb wrote:this story was splashed across the Australian papers today. I am very happy this person has experienced such a dramatic positive result...but the article has some misleading points. The patient states they are "cured" of MS on several occassions, but also indicates they haven't had a follow up MRI yet...so they dont know the effect on their lesions (err...how could MS be cured if there are still multiple lesions?).

The most important thing is that the patient has an improved quality fo life.


A lesion is a scar. Scars don't really go away. But since the brain is plastic, it can work around those scars, once the disease process goes away (no more new lesions/whatever pathology causing "scars") the brain can figure out new ways to work around those lesions=disability goes away (slowly over time).

Simply:

You will still have scars though, if you show up at an MRI. They dont go away, but the brain can make do, if the disease process is halted. Well, that's the theory, anyway.
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Postby Brainteaser » Fri Feb 11, 2011 9:23 pm

It's comforting to know that we can rely on the Murdoch Press for MS news.
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Postby scorpion » Sat Feb 12, 2011 1:13 pm

Brainteaser wrote:It's comforting to know that we can rely on the Murdoch Press for MS news.


Hey it beats the MS blogger's world.
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Re: Stem cell patient's path to recovery

Postby patientx » Sun Feb 13, 2011 8:43 am

Lyon wrote:
scorpion wrote:I am generally not one to post feel good stories but I thought this was interesting:
Yes, there are so many vastly different things that are lumped together as "stem cell treatment" that it would be nice if they ALWAYS specifically explained what specifically they are referring to. This time they mentioned "rebooting" and "replacement" so I'd have to think it's similar to what Freedman does.

It looks like some of the article scorpion posted got edited or cut off. Here's a little more of the same article:
http://www.adelaidenow.com.au/news/nati ... 6004742545

After chemotherapy to destroy the faulty white blood cells, which attacked the sheaths around her brain and spinal nerves, her bone marrow stem cells were harvested, she said.

Six million stem cells were extracted from her blood, then frozen and stored.

She then had a heavy dose of chemotherapy to destroy her bone marrow, which had been producing the faulty cells, she said.

This was followed by her transplant, in which her stem cells were transfused back into her, and her bone marrow started producing healthy blood cells.
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Postby georgegoss » Mon Feb 14, 2011 11:42 am

Thanks for posting the entire article, Patientx. Having done the same myeloablative stem cell transplantation myself, I have these observations from (the brief) article to add. . . .

"But it was too early to call it a cure, as the treatment was first done a decade ago, Dr Andrews said." . . . .

What is the definition of "cure?" There is no universal definition of what a cure is. I found that doctors and patients often have different definitions. It is up to each person to decide for themselves what a cure means. For me it was "stop the disease activity/progression and restore immune self-tolerance." By that definition I am cured from my transplant. Additionally, MRI brain scan lesions have very limited correlation with clinical symptomatic progression of MS (measured by EDSS). A great number of people are "sub-clinical." That is they have Gd-enhanced T2 brain lesions activity on MRI but never manifest any clinical symptoms of MS whatsoever. That's why MS cannot be diagnosed with an MRI scan alone. It also requires physical menifestations of disease activity. Does a person with a positive MRI scan result have MS even though they never have any outward symptoms? I would argue they do not.

"In 70 per cent of patients, there is no evidence of recurrence of the disease over 100 months, but what happens beyond that we don't yet know.". . . . .

This statistic is referring to the first phase I clinical trial in 2000. Unfortunately the brevity of the article leaves out some important info. . . . The first (phase I) clinical trial was done by Dr. Richard Burt at NWU in Chicago where they used a protocol (TBI) that is now evolved into a more effective therapy that does not use TBI. Although only 70% of the patients treated with this obsolete (TBI) protocol had a 'stopping' of their disease progression, not a single person that had their MS disease activity stopped has again shown any evidence of further progression at any time, at all. So it is actually quite likely that anyone that has the MS disease activity stopped (shown to be 100% of the people in the phase II trial, also of which there have been no deaths) will likely have a lifetime disease remission. We just have to first wait until all the treated patients die of old age to prove it. I'm taking bets that will be the final result.

"Doctors had been reluctant to perform the procedure in Australia because it had carried a 10 per cent death rate, but this had now dropped to less than one per cent, although it was still not suitable for all MS sufferers, he said". . . . .

The death rate has indeed dropped to 1% (or less) because the evolved protocol no longer uses TBI, relying soley on a more gentle chemical ablation that so far has shown exccellent curative results. And the article also correctly states that this treatment is not suitable for all MS sufferers, but doesn't say why. Its too bad that they didn't explain a little further which is that stem cell transplantation favors ealy relapsing cases resulting in curatative efficacy (better than 80% of the people also have substantial symptomatic improvement measured by EDSS). Late stage progressive non-ambulatory cases can still have the disease process stopped, but reversal of symptoms (symptomatic improvement) is less likely, or not at all because much of the damage has already been done.

Here is some more info/data on this reference page. . . . .

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

.
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Postby Looking88 » Wed Feb 16, 2011 1:27 pm

Does anybody know if Carmel got the standard BEAM protocol, or if they cleaned her stem cells?

Thanks,
Looking88
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Postby Lyon » Wed Feb 16, 2011 2:41 pm

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Postby georgegoss » Wed Feb 16, 2011 2:48 pm

Looking88 wrote:Does anybody know if Carmel got the standard BEAM protocol, or if they cleaned her stem cells?

Thanks,
Looking88


I have been trying to find a technical refernce for the protocol that Dr. Colin Andrews is using in Canberra but have so far not been able to locate any specific information. I'm sure with more time searching it should be able to be found.

But a hint from a non-technical article from Australia Broadcasting I came across that makes a comment related to this subject. . . .

http://the-riotact.com/canberra-hospital-cures-ms/21720

"Ben was subjected to a second dose of chemotherapy to knock out his immune system and remaining bone marrow cells."

If true, then this is likely a myeloablative procedure, not the lymphoablative procedure as used by Dr. Burt at NWU in Chicago. But this should be verified before assuming this is 100% correct. Perhaps call Dr. Andrews in Australia directly? His local telephone number can be found on this page:

http://health.act.gov.au/c/health?a=&did=10246388
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Postby Looking88 » Wed Feb 16, 2011 3:58 pm

Thanks George. I was pretty sure (I think from the YouTube videos) that this was myeloablative also.

What I am curious about (and maybe I will try that phone number) is if they separated the stem cells from the T cells.

I am wondering if they are using the HALT-MS protocol or standard BEAM.

Thanks,
I will keep looking.

Looking88.
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Postby georgegoss » Wed Feb 16, 2011 6:02 pm

Looking88 wrote:Thanks George. I was pretty sure (I think from the YouTube videos) that this was myeloablative also.

What I am curious about (and maybe I will try that phone number) is if they separated the stem cells from the T cells.

I am wondering if they are using the HALT-MS protocol or standard BEAM.

Thanks,
I will keep looking.

Looking88.


Another good question. I'm sure no general news article would indicate wether or not they isolate or enrich the autograft. However, if it truly is myeloablative, it shouldn't matter one way or the other. The end curative result should be the same.

However. . . if I were to pick a single question with the most valuable & telling answer, it would be "does this stem cell transplantation procedure require re-vaccination of the treated patients?" If the answer is yes, then I think "maybe" the protocol has the highest degree chance of success for lasting curative outcome.

And now as an afterthought I should add. . . . . the primary reason that some (but not all) of the clinical trial protocols isolate the autograft for CD34+ hematopoietic stem cell selection (removing T-cells) is to reduce the probability of inducing a possibly dangerous exacerbation following stem cell infusion (which happened a few times during the phase I trials, but not during the current phase II trials). Autograft isolation is not specifically to improve curative outcome probability and likely provides no added benefit. As I had mentioned in my blog. . . .

[i]Here is a passage from a 2005 technical paper authored by Dr. Richard Burt at NWU Feinberg school of medicine regarding stem cell engraftment solution T-cell depletion specifically for treatment of MS. . . . . .

Most mononuclear cells collected by peripheral blood apheresis are immune cells such as lymphocytes and monocytes not HSCs. While the true identity of human HSCs remains elusive, either purified CD34+ or AC133+ hematolymphopoietic progenitor cells are sufficient for hematopoietic and immune reconstitution. In general, a minimum number of 2 x 10E6 CD34+ cells per kilogram of recipient weight will ensure engraftment. Hematopoietic stem cells may be positively selected or enriched ex vivo using antibodies to CD34+ or AC133 or purified by negative selection by using antibodies to remove lymphocytes. In practice, the most common method of purging lymphocytes is via CD34-positive selection using either the Miltenyi CliniMACS (Bergish Gladbach, Germany) or the Baxter Isolex (Deerfield, Ill) cell separator device. Whether enriching the graft for CD34+ HSC is necessary or even superior to infusion of an unmanipulated graft remains unclear. CD34+ selection by removing lymphocytes is perhaps best viewed as another method of immune suppression. For an intense conditioning regimen, CD34+ selection may be unnecessary or even detrimental by increasing the risk of treatment-related infection..


. . . . the following passage from a 2002 paper co-authored by Dr. Richard Nash titled "High-Dose Immunosuppression and Hematopoietic Stem Cell Transplantation in Autoimmune Disease: Clinical Review" as related to the HALT-MS program use of r-ATG & autograft manipulation (that I did not receive) for the treatment of autoimmune disorders:

http://static.cjp.com/gems/bbmt/BBMT.8.5.Openshaw.PDF

Implications of Immunological Reconstitution

Some investigators have assumed that early relapses of autoimmunity after transplantation are from residual autoreactive T-cells remaining after conditioning therapy or autoreactive T-cells at too high a level in the graft. ATG treatment at the time of stem cell reinfusion is intended to
deplete both reinfused T-cells and T-cells that survive conditioning. ATG has been used in approximately 80% of MS patients in the EBMT registry and is included in the Seattle but not the Northwestern MS protocols. ATG has been used in less than 10% of transplantations in RA cases, in less than 50% of transplantations in SSc cases, and in two thirds of transplantations in SLE cases in the EBMT registry. In North America, ATG is included in the multicenter SSc protocol [64], and ATG was included in the Northwestern phase I SLE trial [57]. Arguments, however, against such extensive T-cell purging have also been made. Reported by S. Millikan and coworkers at the 2000 Basel meeting was an Australian comparison trial showing that CD34+ cell selection did not improve the duration of remission after autologous HSCT in RA (described in [6]). Whether these findings are relevant to other autoimmune diseases remains uncertain. Clearly, if the goal of therapy is primarily anti-inflammatory, then T-cell depletion may be less important. Concerns have also been expressed in terms of the acute toxicity of ATG in patients so ill at the time of their conditioning and the long-term risks of infection and lymphoproliferative disease from the marked immunosuppression after coupling CD34+ cell selection with ATG treatment. Fatal lymphoproliferative disease, attributed to the potent immunosuppressive properties of rabbit ATG given in conjunction with intensive TBI-based immunosuppressive regimens, has been seen in 2 patients receiving HSCT for autoimmune disease [64,65].
[/i][/i]
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