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AA Aplastic anemia

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  #1  
Old Fri May 13, 2016, 02:00 AM
Logain Logain is offline
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A few questions regarding the nature of AA

Hello everyone,

I've attended Dr.Saunthararajah's AA webinar yesterday.
While no new research or solutions were mentioned, the webinar did explain the nature of AA more in depth.

A few questions have risen:

(1) Dr.Saunthararajah explained that the cause for acquired AA is in fact a CHANGE in the patient's stem cells, that could occur due to a great many things.
My question, therefore, is - are ALL stem cells affected by said change, or are there some that remain in their original form and are therefore not attacked by the body's immune system?

(2) Since the disease doesn't destroy your entire bone marrow in a week, as would be the case if the entire immune system took part in the effort to remove the "foreign" stem cell, I deduct that only a FEW T-cells target the marrow. In this case, is it possible to ISOLATE those T-cells, understand why they work differently than the others and try to remove or modify them?

If you don't know the answers to these questions, I would suggest you try asking your doctors (I know I will). There must be a way to solve this!

Thanks for reading!
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  #2  
Old Fri May 13, 2016, 11:04 AM
bailie bailie is offline
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Good questions. I have come to realize that most doctors we come in contact with are reactive rather than proactive for these diseases. They are not research oriented as much as we might expect. I think the research of these diseases is another lane and only peripherally approached by the doctors we generally deal.
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age 70, dx RAEB-2 on 11-26-2013 w/11% blasts. 8 cycles Vidaza 3w/Revlimid. SCT 8/15/2014, relapsed@Day+210 (AML). Now(SCT-Day+1005). Prepping w/ 10 days Dacogen for DLI on 6/9/2017.
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Old Sat May 14, 2016, 12:36 PM
Hopeful Hopeful is offline
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Quote:
Originally Posted by Logain View Post

(1) Dr.Saunthararajah explained that the cause for acquired AA is in fact a CHANGE in the patient's stem cells, that could occur due to a great many things.
My question, therefore, is - are ALL stem cells affected by said change, or are there some that remain in their original form and are therefore not attacked by the body's immune system?
Hi Logain,

I didn't get a chance to see the webinar yet and will have to wait until it is archived.

The way it was explained to me is that there are various stages of blood cell formation, with the most primal being the stem cell. With immune variations of these diseases, the rogue T-cells start attacking/destroying blood cells, first in the blood stream. Left unchecked, they may start to attack/destroy the progenitor blood cells and eventually the stem cells in the marrow. If this happens to enough of the stems cells that are responsible for producing the blood progenitor cell, blood cell productions will be affected. That is why the diagnosis of AA was a death sentence in the days before IST - minimal/no stem cells = no blood.

Left unchecked, the T-cells may also damage some of the stem cells, which is thought to be a cause of immune mediated MDS. In this case, the stem cells still generate new cells but they are dysplastic and non-functioning. Again this is how it was explained to me.

All stem cells are not attacked by the T-cells, which is why after the rogue T-cells are beaten down by ATG, a person's counts may increase and sometimes normalize. Changes will appear in the blood counts before they appear in the marrow.

After ATG/CyA, the rogue T-cell colony is still there, but much smaller. That is why there is the potential for relapse. Hopefully, the body's immune system is strong enough (sometimes with the help of cyclosporine) to keep the rogue T-cell colony in check and prevent them from expanding. Stresses to the immune system (pregnancy, surgery, viruses) will provide challenges though and may result in relapse.

Things that people are exposed to in the environment (or genetically from birth) may cause gene mutations that make them more susceptible to immune attacks or cancer. The longer you live, the more genetic mutations you pick up.

Again, I am not a doctor. This is just my interpretation of how it was explained to me! It may change after I see that video


Quote:
Originally Posted by Logain View Post
(2) Since the disease doesn't destroy your entire bone marrow in a week, as would be the case if the entire immune system took part in the effort to remove the "foreign" stem cell, I deduct that only a FEW T-cells target the marrow. In this case, is it possible to ISOLATE those T-cells, understand why they work differently than the others and try to remove or modify them?

If you don't know the answers to these questions, I would suggest you try asking your doctors (I know I will). There must be a way to solve this!

Thanks for reading!
Dr. Neal Young once had a presentation that showed that they had been able to isolate/track these rogue T-cells. He showed the change in the colony size before and after ATG.

Too bad this video was removed from the AA&MDSIF website! It was really interesting.
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50 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.
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  #4  
Old Mon May 16, 2016, 11:31 AM
Logain Logain is offline
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Quote:
Originally Posted by Hopeful View Post
Dr. Neal Young once had a presentation that showed that they had been able to isolate/track these rogue T-cells. He showed the change in the colony size before and after ATG.

Too bad this video was removed from the AA&MDSIF website! It was really interesting.
Ah, now there's something interesting!
I think I read his research about it, his team found a strong connection between colony size of the CD8+ T-Cells, and the failure of IST and/or severity of AA.
I also know scientists have been able to "train" T-Cells to recognize and attack other cells in the body.

So, from a simple point of view of someone who's not a specialist in either biology/medicine - it seems that just putting those two groups together should yield a cure for AA.
Or I am totally wrong. Always an option.

It's at times like these that I regret not specializing in medicine
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