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AA Aplastic anemia

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  #1  
Old Thu Aug 18, 2011, 03:38 PM
Greg H Greg H is offline
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How Does AA Progress to MDS?

Hey Folks!

Janice M asked an interesting question over in another thread that I thought might warrant its own conversation.

She asked:

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Originally Posted by Janice M. View Post

One quick question, how does AA progress into MDS?
And I said:

Quote:
Since being diagnosed with MDS, I have focused on MDS and not paid nearly as much attention to AA, despite the fact that some of my best buds on marrowforums are AA folks.

Consequently, I don't know the answer to that question, though I would love to understand it better.

My impression is that, in the space that you occupy, with your hypocellular marrow, it can be a bit tricky to differentiate AA from MDS. So "progression" from one to the other may be, I'll bet, not so much a change in condition as a change in diagnosis.

I do think it's an important question, particularly for you. Because the therapies that seem like a good idea for MDS are not always a good idea for AA -- Campath as a frontline therapy being one example: nice results in younger folks with MDS; not so good results as a frontline therapy for AA (with a few exceptions).
So, what do y'all think? How does AA progress to MDS? Or is it a matter of updated (or uncertain) diagnosis?

Thanks!

Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com
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  #2  
Old Thu Aug 18, 2011, 05:05 PM
DanL DanL is offline
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Like most of us, I am no expert on either disease, but it seems reasonable that one of the primary obvious differences is cytogenetic changes, and the other being dysplasia. AA may have mild dysplasia, whereas MDS is defined by 10% or more of the cells in any line being dysplastic. Progression from AA to MDS would come from the same basic drivers that change diagnosis from MDS to AML. Marrow stress and the effect on stem cells and blood production probably leads to the conversion from one type to another.

from the following article (although it is a little older):

http://www.jpathology.com/Issues/Pre...mia_Nadeem.pdf

Aplastic Anaemia (AA) is defined as the presence of pancytopenia in the peripheral blood and a hypocellular marrow in which normal haemopoietic marrow is replaced by fat cells. Abnormal cells are not found in either the peripheral blood or the bone marrow. The diagnosis is based on the absence of cells, not the presence of any characteristic feature1. Myelodysplastic Syndrome (MDS) is a disorder of haemopoietic stem cell and is characterized by variable degree of trilineage dysplasia and cytopenias in the face of a normal or hypercellular marrow reflecting ineffective haemopoiesis 2 . As compared to MDS, aplastic anaemia is more uniform clinical entity. Blood count findings are usually striking, the bone marrow morphology is unambiguous, and the response to therapy is relatively predictable.

just my 2cents.
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MDS RCMD w/grade 2-3 fibrosis. Allo-MUD Feb 26, 2014. Relapsed August 2014. Free and clear of MDS since November 2014 after treatment with Vidaza and Rituxan. No longer experiencing nor treating CGVHD. Working on fixing long-term side effects of AVN in hips and cataracts in eyes. Life is good!
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  #3  
Old Sat Aug 20, 2011, 12:53 AM
Hopeful Hopeful is offline
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This is the way the transformation from AA to hypoplastic MDS was explained to me...

The hematopoietic (or blood-producing) stem cell differentiates to another type of stem cell that further differentiates into the lymphoid progenitor cells (that differentiates to make all the different types of WBCs) and myeloid progenitor cells (which differentiate to eventually become the RBCs and platelets).

If an immune attack is going on, as in aplastic anemia, most of the blood cells will be killed off in the marrow. If the attack continues the progenitor cells further up the line can also be damaged. If this happens, they start to make dysplastic cells. If it happens to enough of the progenitor cells upstream, then the marrow starts to look more like MDS then AA.

One thing that makes the differentiation so hard between AA and MDS is that the marrow is fluid. So, what you see during one BMB aspiration may not be the same thing that you see at your next. For me, I had some BMB's where I was hypocellular and others that were hypercellular.

I don't think this line of thinking necessarily applies to AA that transforms to MDS 5 years after IST, but it does seem to make sense for the initial diagnosis if it is immune mediated.
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52 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 Sat Aug 20, 2011, 04:29 PM
Greg H Greg H is offline
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It's the Dysplasia, Silly!

Thanks Dan & Hopeful!

This makes perfect sense:

If, in AA, "Abnormal cells are not found in either the peripheral blood or the bone macro," then the key difference is the abnormal cells -- i.e. the dysplasia that characterizes myelodysplasia.

I think Hopefuls' explanation of how AA could ultimately morph into MDS makes sense to. The folks at NIH who are messed with IST for MDS believe that, if the immune attack on the marrow continues long enough, the build up of cytokines and other stuff start to damage the stem cells and they make abnormal cells.

Great explanations!

Thanks!

Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com
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  #5  
Old Tue Aug 30, 2011, 08:24 PM
Snuuze Snuuze is offline
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Yikes! Do you guys really understand all the medical terminology? I can't tell you how many times I have read my BMB report and can always learn something new.

My situation is the reverse. I went from MDS to Aplastic Anemia with PNH thrown in for good measure. As far as I can tell, it's just a matter of fine-tuning the diagnosis. I have arrested development white cells, a few mature red cells and absolutely no platelets in my bone marrow. The no platelet condition caused the pathologist to change her previous diagnosis from MDS to SAA. The speculation is that perhaps I had AA all along, but the MDS symptoms were present as well.

I find it very difficult to wade through the medical terms and put into simple English for me to maybe understand.
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Sue, age 72; Dx 6/2010 MDS Int-2. Revlimid unsuccessful, began Aranesp 10/2010; additionally Dx PNH 2/2011, Soliris added 3/2011. ATG 5/2011, Cyclosporine 5/2011. Nplate 10/2011 to 10/2012 . Exjade began 12/2013 due to high ferritin level, discontinued 3/2014 because of increase in creatinine.
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  #6  
Old Thu Sep 1, 2011, 11:26 PM
Greg H Greg H is offline
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Sue,

I find all the medical terms a major pain in the behind. It's kind of like a secret language that helps preserve the authority of the medical priesthood. Only folks who know the secret words are qualified to think about this stuff.

Baloney.

There is plenty of stuff that is way, way over my head -- particularly when you start talking about the way that genes work.

But some stuff . . . here's a good example: anisocytosis. You read that in your BMB report and think, "Holy moly! Whatever could that be? I must have bubonic plague or something. Or maybe my toes smell like anise seeds! Yikes!"

Turns out it means you have unequal-sized red blood cells -- just one of the many delights produced by out of whack bone marrow.

I think it would be a lot easier if they just said "We saw red blood cells of unequal size," don't you? If they'd just do that, I wouldn't have to look that dang word up every time I get a new BMB report.

Take care!

Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com
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  #7  
Old Thu Sep 8, 2011, 02:03 AM
cathybee1 cathybee1 is offline
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Have you also noticed that once you start throwing terms like this back at medical professionals, they slit their eyes and look at you with suspicion.
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Catherine, wife of Bruce age 75; diagnosed 6/10/11 with macrocytic anemia, neutropenia and mild thrombocytopenia; BMB suggesting emerging MDS. Copper deficient. Currently receiving procrit and neuopogen injections weekly, B12 dermal cream and injections, Transfusions ~ 5 weeks.
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  #8  
Old Thu Sep 8, 2011, 10:26 AM
DanL DanL is offline
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it is funny in a sad way. one of my docs wont go into any real detail and thinks that it is a waste of time to discuss the details and what they mean. he is regularly listed as one of the best hem-oncs in the area. my transplant doctor will spend two hours reviewing and telling me why something is important or not and what to look for in the future. i like them both, but really do need the explanations in order to sleep at night.
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MDS RCMD w/grade 2-3 fibrosis. Allo-MUD Feb 26, 2014. Relapsed August 2014. Free and clear of MDS since November 2014 after treatment with Vidaza and Rituxan. No longer experiencing nor treating CGVHD. Working on fixing long-term side effects of AVN in hips and cataracts in eyes. Life is good!
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  #9  
Old Thu Sep 8, 2011, 03:51 PM
Neil Cuadra Neil Cuadra is offline
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The doctors I've worked with use medical terminology (full of big words like "trilineage dysplasia") because they need to be precise when they work with each other and when they exchange data and research papers.

Their challenge is to meet laypeople at least halfway. Clearly, some doctors are better at this than others, and patients who only listen and nod their heads may leave doctors unable to tell which parts you understand and which parts you don't. Yeah, there are no doubt some bad apples who don't care to explain things to you in terms you'll understand, but I think they are the exception and that the time pressure of short appointments is at least as much to blame.

Bone marrow biopsy reports are written by medical specialists for other medical specialists. It's only in recent years that we patients have started asking for and receiving copies of them. It's not a surprise that we can't easily interpret them. We could sure use some medical-to-English translation software!

It's the same in my profession (computers). We don't speak in computer lingo and our infamous acronyms to impress people. If I say "I need the software for the database" to my coworkers they won't know which type of software I need for which type of database. I have to say "I need a single-tier ODBC driver for the RDBMS" instead. It's the same with other technical fields (biologists, financial advisors, architects). I can hold my own in some of these fields, but when the auto mechanic explains what's making that funny noise in my engine, he sometimes gets too technical for me and I find myself silently nodding my head.
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  #10  
Old Fri Sep 9, 2011, 03:13 AM
Lisa V Lisa V is offline
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Sometimes doctors can go too far trying to put things in layman's terms, though.

This is a bit off the AA/MDS topic. I have a dermatologist who I like very much, but he has developed a whole repertoire of analogies that he uses which probably appeal to a lot of people, but which I find a bit too dumbed-down to be really helpful. Some of his patients may be satisfied with the explanation that a topical medication "acts like PacMan and gobbles up all the bad cells", but that doesn't really explain how it works, and how it "knows" which cells to destroy. Upon further questioning, I was able to extract from him that precancerous cells have a higher metabolic rate than normal cells, and that the medication is designed to detect that and respond to it. That still isn't highly technical medical terminology and doesn't go into the specific biochemical mechanisms involved, but that was the level of explanation I needed. I just had to let him know how much I was capable of understanding so he could adjust his approach.

The same is true for the hem/oncs. It helps to engage in a dialog and let them know how much you already understand and how much you want to know. Some are easier to talk to than others, but a good physician will welcome active participation. Of course if you start throwing around a lot of big words without a fully confident understanding of what they mean, rest assured that they will pick up on it and may try to put you in your place. Doctors have egos, and they don't like a know-it-all any more than the rest of us do.

Meanwhile, back to the original question of transformation....... I can understand how AA can morph into hypocellular MDS with the development of chromosomal mutations which may be more efficient at cloning themselves than healthy cells. What I am less clear on is how or why a hypocellular marrow transforms into a hypercellular one, as most MDS is. Or are most cases of AA > MDS transformations to hypo MDS? Also, can an auto-immune condition transform into one that is not?
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  #11  
Old Fri Sep 9, 2011, 06:00 AM
squirrellypoo squirrellypoo is offline
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Quote:
Originally Posted by Lisa V View Post
Sometimes doctors can go too far trying to put things in layman's terms, though.
Lisa, what's worked for me with several different new doctors is that I explain from the outset that I've got a biology degree so they only need to dumb it down slightly and I'll let them know if they need to explain it further. In every single one of those cases, a look of relief washed over the doctor's face and then they started in on a real medical explanation that was helpful to us both. Don't be afraid of letting your doctor know you want the medical details!
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36/F - 1984 SAA treated with ATG [complete remission until] Oct 08 - burst blood vessels in eyes and low platelets; Jan 09 - AA & hypo-MDS; July 09 - BMT (RIC MUD PSCT) July 10 - 10k for Anthony Nolan (1yr post BMT! 53:48) Sep 10 - Wedding! I've run 5 marathons now!! (PB 3:30!)
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