MDS Diagnosis - Odd Experience

[steve_ky]

I'm posting to seek advice regarding my father. See questions below.

He is 73 years old and was just diagnosed with intermediate risk MDS. His red and white counts were just outside of the low end of the normal range. No blasts were detected. However, his platelets ranged between 24,000 - 27,000 over 3 CBCs.

We've worked with two oncologists. The first doctor immediately prescribed Vidaza and told my father he could live up to 2 years. We paused for a second opinion from another (more experienced) oncologist. The second opinion doctor examined the test results collected by the original doctor. His initial impression was that my father may only have very low risk MDS - if at all. And, he wouldn't pursue Vidaza like the original doctor for at least 8-10 years.

We chose to go with the 2nd opinion doctor. During this initial visit he performed a thorough round of tests, including a CAT scan to examine the liver and spleen.

One week later, the family arrived for a second appointment to hear the new diagnosis. The doctor indicated that my father may have MDS, but he is puzzled by the test results. Said his platelets dropped to 13,000 - yikes! However, his red and white cells were low but stable, and still no blasts were detected.

The doctor stated the he'd like my father to visit an MDS center of excellence to see a leading platelet specialists. And, he prescribed Vidaza shots 1 week from the day of the 2nd office visit.

Our family goes through 2-3 days thinking dad still has a chance because only his platelets are affected. I have a follow up call with the doctor to confirm our understanding of my father's status and treatment plan.

I learn the following during this conversation:

1. Doctor is certain he has intermediate risk MDS.
2. He can't travel to the chosen MDS center of excellence until he's stable because of the risk.
3. He has pancytopenia instead of just thrombocytopenia.
4. Vidaza could take months to work (if at all), and he will need transfusions to keep platelets > 10,000.

The doctor's direct and sharp delivery of this information was alarming. Neither my mother nor father received any of this information during that 2nd office visit.

Questions:

1. Should I be alarmed by the reassurance this doctor offered our family during the first visit, and prompt reversal during the 2nd visit - i.e. after providing an opinion based upon reviewing the prior doc's test results?

2. Can platelets drop from 24,000 to 13,000 in 6-days time?

3. Should we seek a 3rd opinion before starting Vidaza?

4. Could side effects from the blood pressure and cholesterol medications explain the thrombocytopenia? My father takes 3 medications daily that list Thrombocytopenia as a potential impact.

Thanks in advance for evaluating my plea for advice.

[Birgitta-A]

Hi Steve,
Very important for your father to see a platelet specialist!

1 Your father can perhaps have ITP - Immun Thrombocytopenia with much better prognosis than MDS.

2 Directly after a platelet transfusion your father perhaps could travel. Prednisone and similar drugs very often increases platelets but are not OK for long term treatment.

3 His pancytopenia is not serious with HGB and WBC just outside the normal range. Many diseases could give that kind of results.

4 Your info about Vidaza is correct. Perhaps the platelet specialist will give your father Eltrombopag/Promacta - a drug for low platelets.

Questions:
1 We hope that your father will be able to see a platelet specialist after platelet txs and Prednisone.

2 Platelets very often jump - it is important that they function well. If they are dysfunctional your father should have small bledings from mouth and nose, small skin bleedings called petaechia and bruises.

3 If you are looking for a third opinion you should try a platelet specialist.

4 There are many drugs that can cause low platelets or prevent blood clotting. All kinds of pain killers skouls be avoided. Here is a warning list: http://www.pdsa.org/about-itp/warnings.html

Kind regards
Birgitta-A
75 yo, dx MDS Interm-1 2006. Positive results with Thalidomide and Revlimid

[Hopeful]

Hi Steve,

What did the second doctor see in the bone marrow biopsy that led to a "confirmed" MDS diagnosis? Did he have any cytogenetic abnormalities? If so, which ones? Did he have significant cell dyplasia? What was his bone marrow cellularity like?

As Birgitta mentioned, there could be other possible causes. It would be prudent to be confident in the diagnosis before starting a powerful drug like Vidaza.

How frequently are the CBCs? Does your father have an illness right now that could be contributing to the drop in platelets? What is his platelet count now?

Can your father switch the medication that lists thrombocytopenia as a side effect?

How is your father's clotting factor? Does he have any symptoms of the thrombocytopenia?

I would seek the third opinion unless I understood what confirmed the MDS diagnosis. Get a copy of the bone marrow biopsy report, if you haven't already.

[bailie]

Vidaza can have terrific results depending on how long it is effective. Without Vidaza I would have considerable more problems. My blood counts except the blast count are all in the normal range. Up until getting the Vidaza my counts were deteriorating quickly seven months ago.

[steve_ky]

All,

Thanks for the quick responses. My father had 4 CBCs and 1 BMT taken within a 3 week time span. Can't really speak to the specifics of the bone marrow, however, the second doctor indicated that it appeared healthy.

I plan to visit my parents today to obtain copies of all test results. I'll post the numbers here tonight.

Thanks all!

[sbk007]

I think it would be helpful to you if you could ask the second doctor why his first exam prompted him to tell you it was most likely low risk MDS if at all and then his second visit reversed so as to agree with the first doctor.
It might be uncomfortable to put him on the spot but a lot of time its justified. What is it that changed the 2nd doctors recommendation to match the first doctors recommendation. OF course the best thing would be to get him to a center of excellence where they see MANY patients with these diseases. Most local docs/hematologists have maybe a few patients with these rare diseases whereas the COE's have clusters.
All the best

[Cheryl C]

How is it possible to have an MDS diagnosis and "healthy bone marrow"? Very confusing for you! Hope you can see an experienced haem/onc soon.

[steve_ky]

This post includes the CBC test results for May 30th, June 3rd and June 16. The Bone Marrow Biopsy (BMB) test results from 5/27 are provided as well. Please review and provide feedback if any additional indications may be gleaned from this information.

Answers to questions above:

• There were no cytogenetic abnormalities.
• The 2nd doctor didn't perform a second BMB. He provided his initial opinion of mild or non-existent MDS based upon a review of the CBC from 5/30 and the BMB test produced by the 1st doctor.
• Regarding illness, he doesn't have any chronic problems. However, he came down with a fever/chills and joint paint on May 22rd. This is what prompted the initial office visit with his general practice doctor. Amoxillin was prescribed and he responded well in a few days.
• We plan to contact his GP doctor on Monday to explore the idea of changing blood pressure medication.
• His symptoms which may be consistent with thrombocytopenia include minor fatigue and a rash on his thighs which is healing. Interesting that he presented the rash to the 2nd doctor, but he dismissed its relevance to the case.

CBC Results

30-May........PLT @ 25, WBC @ 3.45, RBC @ 2.56, HGB @ 9.5, HTC @ 28.4, MCV @ 110.9, MPV @ 10.1
03-June.......PLT @ 17, WBC @ 2.71, RBC @ 2.32, HGB @ 9.3, HTC @ 25.8, MCV @ 111.2, MPV @ 9.9
16-June.......PLT @ 13, WBC @ 3.25, RBC @ 2.32, HGB @ 9.4, HTC @ 26.2, MCV @ 114.7, MPV @ 11.1

Bone Marrow Morphology Analysis (from 1st doctor)

Clinical Summary & Indication
Macrocytic anemia and thrombocytopenia. If non-clonal causes of dysplasia can be clinically excluded, the findings are compatible with myelodysplastic syndrome. Blasts are not increased. The findings correlate with the flow cytometric analysis.

Aspirate

Cellularity

• Cellularity is appropriate for age.
• Erythroid precursor show mild dyspoiesis (megaloblastoid maturation and cytoplasmic vacuoles).
• Myeloid maturation is synchronous and progressive.
• Blasts are not increased.
• Auer rods are not observed.

Bone Marrow Biopsy

Microscopic Result

• Core contains ~ 3mm in aggregate of evalluable marrow which is varibly cellular (20-80%).
• The more cellular areas show maturing trillineage hematopoiesis.
• Rare megakaryocytes are present which show dyspoiesis (separate nuclear lobes).
• No lymphoid or plasma cell aggregates.
• No increase in mononuclear blast like cells.
• Bony trabeculae are uncremarkable.
• No detectable iron staining.
• No increase in reticulin fibers.

Biopsy Clot

Microscopic Result

• One clot section is reviewed. It is adequately spiculated.
• The cellularity is mildly increased for age (50-60%).
• There is maturing trillineage hematopoiesis.
• No increase in mononuclear blast like cells.
• The M:E ratio is within normal limits.
• Immunohistochemical studies highlight rare CD34+, CD117+ blasts. They comprise < 1% of total cells.
• MPO and CD71 highlight a mildly increased M:E ratio (~8:1). CD71 highlights few scattered megakaryocytes, many of which are micromegakaryocytes. They do not form clusters.
• Rare storage iron is observed.

Immunohistochemistry

Marker ............................Result ................................Description
CD34 (QBEND-10) ...............Rare Cells Positive ................Endothelium, Stem Cells, Blasts, GI Stromal Tumor.
CD117 (S) ..........................Rare Cells Positive ................Myeloid and Mast Cells, Gastrointestinal Stromal Tumor (c-kit)
Myeloperoxidase IHC ............Myeloid Cells Positive ............Meyloperoxidase, Myeloid LIneage Cells
CD71 (10F11) .....................Erythroid Cells Positive .........Erythroid precursor and large cell lymphoma.
CD61 .................................Megakaryocytes Positive .......Glycoprotein IIIa, Megakaryocytes, Platelets

[maggiemag]

Hi there. I just want to add that there are several other causes for macrocytic anemia than just MDS. Those basic causes like B12 deficiency need to be ruled out as well. The thromobcytopenia seems to be the main concern, with ITP looking as a possible cause. I would agree with the others that heading to a MDS Center of Excellence would be the best next step.

[Hopeful]

Steve,

You may want to talk to the GP about the GI stromal tumor finding as well and whether that could be contributing to the platelet problem or whether that is something separate to investigate. It seems like the report is saying to rule out the "colonal cause of dysplasia" before making an MDS diagnosis. My guess is that "colonal" is not a typo but means pertaining-to-the-colon or GI tract.

[steve_ky]

Hopeful,

Colonal was a typo. It should be clonal and this has been ruled out by both doctors. I've corrected it above.

Also, the term "GI stromal tumor" appears in the description section of the CD34 marker test. The result reads "Rare Cells Positive", however, I don't know how to interpret it.

He starts Vidaza today.

Thanks

[steve_ky]

I would like for someone on this forum to read the bone marrow test results above and comment. Do my father's results match with people who have MDS?

FYI - Vidaza treatment was postponed. Nurse wouldn't give the shot because his platelets were at 12k. He received a platelet transfusion instead. Going back this afternoon for the Vidaza shot if his platelets are up.

We are attempting to switch his blood pressure & cholesterol medications this week to those without thrombocytopenia side effects.

[Hopeful]

Hi Steve,

Let me preface by saying that I am not a doctor just a bone marrow failure patient with 5.5 years of experience

It seems like the immunohistochemistry is just listing possible reasons why those markers would be expressed. I use to just get my markers with no explanations. So that was why I was concerned about the GI stoma notation.

Based on the rest of the report, it could be MDS or it could be something else. The traditional "smoking guns" are cytogenetic abnormalities, blasts, or significant dysplasia. He does have dysplasia in his platelet line, but he also doesn't have a lot of platelet precursors (megakaryocytes). So to me, it is not obvious.

I would seek out that third opinion from an MDS Center of Excellence. Also, keep aggressively pursing a switch in the medicines.

[maggiemag]

Hi Steve. I know little about the immunohistochem., but I can tell you that no increase in reticulin fibers is a good thing and means no fibrosis. The maturing trillineage hematopoesis is great; meaning all three cell types are being produced to mature cells. You already know that no excess blasts and normal cytogenetics are also very good. It seems that both samples were of adequate quality, and if you get another opinion, they may not feel the need to repeat the test. And not much dysplasia, so maybe not MDS. Good luck to you and your father.

[steve_ky]

My father completed his first 7-shot cycle yesterday. His WBC increased from 3.25 to 6.31 which falls within the normal range. All other counts were virtually the same, except for his platelets. They are now at 29k after a transfusion with brought them up to 53k 8-days ago.

I don't believe Vidaza could account for the increase in WBC. Does anyone know if this increase is a good/bad sign?

[bailie]

That is a very good (and very fast) reaction to the Vidaza. I would think that something else is in play to cause that result. Usually it takes longer. My counts "bottomed out" after the second cycle and were either normal or very close by the sixth cycle. Generally, the sooner the response the better.

[kris]

I am so sorry for your family and the confusion you feel.
My husband responded to Vidaza after the second round. I too encourage you to get to a center of excellence for MDS.
Prayers for your father.

[steve_ky]

Doctor changed his diagnosis to MDS-U (unclassified). Does anyone know where I may find good information regarding this classification?

[Cheryl C]

One helpful website for MDS in general (though I don't think MDS-U) is mentioned) is http://theoncologist.alphamedpress.o...t/2/6/389.full

The following article mentions MDS unclassifiable a few times: http://ajcp.ascpjournals.org/content/132/2/290.full.pdf

[Birgitta-A]

Hi Steve,
You have probably already read the WHO classification and the last of the two articles that Cheryl C posted. This article contains info that is much the same.
http://www.bloodjournal.org/content/...-text.pdf+html

I think patients in this group are treated like other patients with low risk MDS.
Kind regards
Birgitta-A

[steve_ky]

Update.. My father completed 2 rounds of Vidaza. During the 1st round, his platelet count fell to 3,000 due to Vidaza, but then it bounced up to 22,000. During the 2nd round, they fell to 16,000 only to bounce up to 29,000 a week later. Three weeks after the 29,000 result, his platelet count jumped all the way up to 122,000. RBC, WBC and HGB are all up too.

The doctor decided to continue with Vidaza for at least 2-3 more rounds. I'm skeptical that Vidaza could have this type of impact after only 2 months. What do you guys think?

[DanL]

Steve,

Vidaza can have that kind of an impact on blood counts with only two cycles complete. There have been a few studies that suggest that an early platelet response where the platelets at least double in the first couple of cycles is a good indicator that the treatment will be effective.

Normally doctors will continue administering Vidaza until a best response is achieved or even longer - I have seen studies that suggest that best response could come along as late as 11 cycles in some patients.

As you probably already know, in the absence of disease progression, Vidaza is recommended for a minimum of 4-6 cycles to obtain best response.

It is really good to see your father responding well.

[sbk007]

Steve,
>> I'm skeptical that Vidaza could have this type of impact after only 2 months. What do you guys think?<<

I responded after round 1 and I've seen others do the same if not with Vidaza, Dacogen. So, yes it is absolutely possible to get a response that quick. Its a good sign - hope it continues. The standard of care is to continue Vidaza until it stops working or the side effects are worse than the benefit and that varies amongst patients.
All the Best!!

[Whizbang]

steve_ky,

I'm with sbk007 (also steve), that (one)/two rounds is sometimes enough for an incredible response...

I had two rounds of dacogen (similar to Vidaza) last summer, and ALL my counts went to from 50-75% of the minimum - all out of range, to basically high range of normal... My post chemo BMB/BMA even showed full remission...

So it is more than possible for these chemo agents to work fast and nothing short of incredibly...

All the best to you and your Father, and may God Bless...

[steve_ky]

Update... Our oncologist was shocked at the latest CBC results after the 4th cycle. My father's platelet count jumped to 335,000. RBC, WBC and HGB counts improved to the lower end of the normal range. We don't know what to make of these results.

Does this type of remission occur?

How long could it last?

The doctor stated that he would consult with an MDS expert from the Mayo. My father just completed a 5th cycle last week. We hope to learn more during our next appointment for Thursday.