MDS Questions

[rich7]

Hello,

I am a 40 year old male and my recent BMB shows moderately hypocellular marrow at 30-40 percent with mild myeloid hypoplasia. Also, it shows mild erythroid megaloblastoid changes and mild megkarycoytic dysmorphic features.

My blasts are 2 percent, WMB is low 3.2, basophils high at 1.2, neutrophil low at 1.5. My RBC is 4.88 and platelet value at 209 while my HGB is 15.8. My WBC three to four years ago hovered around 8.

I initially went to Mt. Sinai after referred for possible Polycythemia Vera which is ruled out and now they feel it is MDS. It's been 4 months and no answers and they sent my sample back out for more in-depth testing.

I have extreme fatigue, always cold, constant pruritus, chest pain, and general weakness. So I am here asking if anyone has any insight after seeing my results what to expect or if anyone has similar findings and what your situation is? Can I get help decoding these results?

Thank you all

[DanL]

Rich7,

I am sorry that you are in limbo about your condition currently. It can be frustrating and nerve-wracking. I was initially diagnosed with ITP due to low platelet counts and otherwise normal counts, but my platelets were dysplastic, or abnormal once we completed the bone marrow biopsy.

Anything that I mention here is solely based on my experience, observations, and research on MDS and blood disorders. I am neither a doctor, nor a researcher, nor scientist of any kind, so please take any information with these disclaimers in mind.

MDS is very rare at your age (and mine - i was diagnosed at 36), Without prior treatment for some other cancer. De Novo MDS under the age of 60 is pretty uncommon, but does happen.

Dysplastic cells can be caused by other immune related problems, or even vitamin deficiency, so a diagnosis may be difficult to confirm without clear markers of MDS, such as cytogenetic changes, gene mutations, or very clear dysplasia in more than 10% (i think) of cells analyzed.

The extreme fatigue, pruritis, chest pain, and weakness, doesn't seem to be typical for a person with such high RBC and HGB counts, but they are common in people with low counts.

As for deciphering results? HGB is solidly normal, as are RBC and platelets. WBC is a little low, but they fluctuate greatly in response to viral infections, bacterial infections, immune issues, etc. As an example, within the past month my whites have been from 4500 (low normal) to 15000 (elevated), as i was fighting an infection that then was treated with antibiotics and brought the count back down. Viral infections can really eat away white blood cells. Blasts at 2% in the marrow falls within the normal range (anything less than 4% is generally considered normal). 2% in the peripheral blood is considered a poor sign.

Hypocellular marrow is atypical in mds, but does occur in about 15% of cases, normo-cellular and hyper-cellular is more common. The megaloblastoid erythroid cells means that red blood cells are making it into the blood stream too early in the maturation process. mild megakaryoctic dysmorphic changes indicates a problem with either the creation or maturation of your platelets.

Just looking at what you provided, it appears that there is some stress on the marrow, but the cause is uncertain. Many blood diseases are determined by process of elimination, meaning that they are diagnoses of exclusion - which sometimes means a lengthy process.

Four months seems like a long time to get results to me. If you can, get a copy of your biopsy and peripheral blood smears to a center that specializes in blood diseases to help move the process along for you. This shouldn't take any more than 3 weeks based on my experience.

I hope that you get answers soon.

[rich7]

Thank you Dan, I appreciate the information. As an update, my biopsy was sent back out for more testing and came back with the MLL gene mutation. What does this mean? I am now to go back in 3 months as he sees the issues with the bone marrow and MLL gene but he says I don't have all of the symptoms. I feel the longer I wait, the worse it could get and in 3 months, it will be 8 months. Any thoughts?

[Jill2008]

I also had a hypocellular marrow 30-40% and blasts less than 5%, but it was mainly my platelets that were affected. I had fatigue and bruising that prompted me to schedule an appointment for a physical. I was sent for a bone marrow biopsy and was told I had a vitamin B-12 deficiency (even though I had four chromosome abnormalities). Initially B-12 injections helped, but then my platelets started dropping again. After 6 long months, I was finally referred to Stanford where they requested my slides, etc. to obtain their own biopsy results. The results showed that it could be MDS, but further testing was needed for a definitive diagnosis. My hematologist, however, was 99% sure that I had MDS. In retrospect, I should have sought a second opinion but I was at a Center of Excellence for MDS. As a search for a donor began, I stopped working and my counts stabilized. I was then on watch and wait for nearly 2 years and then Monosomy 7 showed up following another biopsy. From what I understand, being a woman under the age of 55 at the time, with a hypocellular marrow meant that the MDS was probably brought on by an autoimmune attack. I was diagnosed with Raynauds around the time that the fatigue and bruising started, so this made sense. Unfortunately, genetic testing wasn't common place back when I was diagnosed.
Have you considered a second opinion at a Center of Excellence?

[rich7]

Thank you Jill. I think a second opinion at a center for excellence is needed. I too have an autoimmune where I have a postive ANA but might not be full blown SLE Lupus. I just feel considering what the results show and being 40, I shouldn't wait 8 months to figure this out. What is the MLL mutation?

[Jill2008]

Hi Rich,

I know there are certain gene mutations responsible for MDS, but genetic testing wasn’t done at the time I was diagnosed. I recommend that you contact the MDS Foundation @mds-foundation.org or the Aplastic Anemia and MDS International Foundation @aamds.org. They are both great resources and you will be able to find a list of the MDS Centers of Excellence there. I hope you get some answers soon!

[Hopeful]

Hi rich7,

I concur with the others that now is the time to seek out second opinions with other experts in the field of bone marrow failure and autoimmune disease (not just MDS).

Your counts are good right now. Nothing that you have posted screams MDS. However, a quick google search will tell you that the MLL gene mutation isn't a good one to have. There is something going on, but the doctors probably aren't sure of the diagnosis yet, and there is no standard-of-care for treatment for this mutation. This is the problem with being on the forefront of advance genomic testing - what to do with the information!

I think it would be wise to use this time while you are "stable" to build a team of experts, so that you have direction if things transform.

Be well!

[Pearl]

Originally Posted by rich7

Thank you Jill. I think a second opinion at a center for excellence is needed. I too have an autoimmune where I have a postive ANA but might not be full blown SLE Lupus. I just feel considering what the results show and being 40, I shouldn't wait 8 months to figure this out. What is the MLL mutation?

I have seen mention of MLL mutations, and I remember it is generally not a good thing, but I do not know in any detail they mean. I am not sure where you are, but get to an MDS Center of Excellence so you can talk to someone who does.

[rich7]

Thank you all. Makes you wonder why the doctors attitude is so lax at times unless my results are not an issue. Maybe its possible that these things are no big deal without full blown symptoms? I did notice some things in doing my own research and trying to decode the BMB results and I wanted to ask what this means:

Dysmegakaryopoiesis

Dyserythropoisesis

Hypocellular marrow

CD 71 shows erythroid precursors

MPO shows myeloid precursors

CD 61 shows megakaryocytes

These are on my biopsy results along with the diagnosis section showing myeloid hypoplasia, erythroid megaloblastoid changes, and megakaryocytic dysmorphic changes.

[Hopeful]

Originally Posted by rich7

Thank you all. Makes you wonder why the doctors attitude is so lax at times unless my results are not an issue. Maybe its possible that these things are no big deal without full blown symptoms? I did notice some things in doing my own research and trying to decode the BMB results and I wanted to ask what this means:

I can try and help with some of this:

dys = abnormal
poiesis = the development of

So...

Dysmegakaryopoiesis = the abnormal development of megakaryocytic (platelet precursors)

Dyserythropoisesis = the abnormal development of erythroid cells (RBC precursors)

Hypocellular marrow = less blood cells in the marrow than what is normal for someone your age.



I can't really comment on what they were looking for below in the flow cytometry report:

Originally Posted by rich7

CD 71 shows erythroid precursors
MPO shows myeloid precursors
CD 61 shows megakaryocytes

The comments below are saying similar things as above in that there are abnormal shapes in the cells that are to become your red blood cells and platelets. Many things can cause these changes - some are more benign than others.

Originally Posted by rich7

These are on my biopsy results along with the diagnosis section showing myeloid hypoplasia, erythroid megaloblastoid changes, and megakaryocytic dysmorphic changes.

If you have a mild number of dysplastic (abnormal) cells, the normal ones may be able to compensate. Sometimes the marrow is able to heal itself, which may be why your doctors are waiting to see how this develops.

They also may not have enough data to interpret the MLL mutation in the absence of lower counts. I am not sure that there is anything that they could do to treat you at this point, assuming they have done all the other standard deficiency and differential tests.

I can imagine that this is very unsettling - especially not doing anything! That's why many are suggesting that you get other experts involved, especially given the MLL mutation and the SLE. I consulted with multiple experts when trying to get my diagnosis. They each had invaluable contributions for tests, treatment options, and timing. If I didn't do the outside consults, I probably wouldn't be here typing this message! Knowledge is power - especially when dealing with rare conditions. The experts in this field will be eager to talk to you.


I am not a doctor but hope my experiences can help you.

[rich7]

As an update, more results show a “copy neutral loss of heterozygosity” of the 5q Gene. CN-LOH of the long arms of chromosome 5q is recurrent abnormality and in MDS it may be associated with adverse survival. What does this mean?

[Leigh Clark]

Originally Posted by rich7

As an update, more results show a “copy neutral loss of heterozygosity” of the 5q Gene. CN-LOH of the long arms of chromosome 5q is recurrent abnormality and in MDS it may be associated with adverse survival. What does this mean?

Hi - this is Leigh with the Aplastic Anemia and MDS International Foundation. I reached out to one of our MDS experts for help in answering your question. In simple terms, this is equivalent to being diagnosed with 5q- MDS and does not mean adverse survival. If you would like to get a second opinion, I'd he happy to help with referring you to experts. You can email me at clark@aamds.org. I hope you have a nice weekend.

[rich7]

Thank you Leigh! I emailed you!

[Barb]

Leigh, I'm so grateful you knew that was the same as 5q-. I thought it was but I didn't want to speak out until I was sure. Rich, 5q- by itself is indeed a good thing. If you are going to have MDS, it's the kind to have. The concern comes when 5q is combined with other genetic mutations. Suddenly, that simple and relatively benign 5q can be associated with a poor prognosis.

That's what happened to me. I went from 5q-syndrome, stable for 12 years to picking up additional mutations (unusual for 5q syndrome), and I now have a high risk, poor prognosis acute leukemia. A second opinion would be wise for you. I'm glad Leigh can help you out.

Blessings

[rich7]

Barb, thank you for your input. I am sorry to hear your situation and wish you the best. At the AA-MDS conference this weekend I did get some answers and like you, it seems the 5q is low risk unless you have other mutations. I was told I have 5q and the MLL mutation so those two together are not good and can lead to AML as I'm sure you know. I am waiting to see the results and actually read them to confirm about the MLL as I only got one back indicating 5q along with the BMB showing moderate hypocelluarity and dysplasia.

What other mutation do you have?

[Barb]

Rich,
When I was first diagnosed with MDS, I had only the 5q-. They did not do genetic testing them only chromosome testing. I have what's called the TP 53 mutation, which I read is the worst type of AML to have. My current karyotype is complex:
44,XX,del(5)(q13q31),-9,der(17)t(17;21)(q11.2;q11.2),-21,+mar[cp11]/46,sl,+
6,del(8)(q24q24),+9,-mar[5]/88,slx2[cp3]/46,sl,+8,+9[cp1]

The TP53 mutation has to do with chromosome 17 missing the tumor protien 53. I believe the MLL gene is on chromosome 11. I have that one too.

My transplant doctor feels confident she can be successful with a transplant. She is concerned that because of the TP53 the leukemia is likely to return so I'll be on long term
treatment after the transplant. I don't know the details of that yet as I'm just focused on learning to live a life that revolves around chemo and blood counts and preparing for transplant.

I wish you the best. Are you doing the second opinion? Let us know how you are doing.