In 2015, I was diagnosed with ET based on platelet levels and Jak2. Treatment has been daily aspirin. At the time (and over the years), my doctor (not an MPN specialist) did not think a BMB was essential.
I switched doctors last year to an MPN specialist. Through discussions with him, coupled with things I have learned (through places like this), I decided it would be valuable to get a BMB. I have always been worried about progression, and wanted to ease my mind - or know definitely so action could be taken if needed.
Since I have become educated about MPNs, I have always been told that the BMB is the only way to truly diagnosis an MPN. So imagine my surprise when my BMB results were equivocal - signs of ET and pre-fibrosis primary MF (not secondary MF). I will obviously be talking to my doctor, but it won't be for several weeks. So in the interim, I thought I would reach out to the knowledgeable folks here and see if anyone has had a similar experience. And if so, how did things play out over time?
Written by
LT55
To view profiles and participate in discussions please or .
There are a variety of reasons why a BMB might be equivocal. It could have something to do with the quality of the sample. it could be your MPN is one that does not fall neatly into one of the classic MPN profiles. If you have the entire BMB report, you may be able to tell the difference by reading though it carefully; however, your MPN Specialist will be the source of truly understanding what the report means in your case.
Please do let us know what you learn. Everyone can benefit from your experience and knowledge.
Thank you for the response. There is a lot to read through on the report. Of course much of it (most of it) I don't really have a good grasp on the importance of, the impact of, etc. I have shared the "final diagnosis" from the BMB report below for the nosy/interested! Will report back when I talk to the doctor, but won't be until April.
"FINAL DIAGNOSIS: Bone marrow aspirate and left posterior iliac crest bone marrow core biopsy:
JAK2+ myeloproliferative neoplasm involving a mildly hypercellular bone marrow (~60% cellular) with increased megakaryocytes, myeloid predominance, and no increase in blasts. See comment.
Flow cytometric immunophenotyping performed on the bone marrow aspirate does not show an increased or atypical blast population.
Comment: The patient's longstanding history of isolated thrombocytosis is noted. Concurrent Next Generation Sequencing (NGS) shows JAK2 and DNMT3A mutations. The overall findings are compatible with a JAK2+ myeloproliferative neoplasm (MPN), with features suggestive of essential thrombocythemia (ET). However, some of the features, such as the increased bone marrow cellularity (~60% cellular), increased M:E ratio (~5: 1), and variable megakaryocyte morphology (including small hypolobated forms), also raise the possibility of pre-fibrotic primary myelofibrosis (pre-PMF). Special stain for reticulin does not highlight increased reticulin fibrosis and no tight megakaryocytic clusters are identified, which favors ET. Cytogenetic studies are pending. Clinical correlation is suggested."
There is a lot of good information in this summary. Proper interpretation will require that the cytogenetic studies be completed and your MPN Specialist needs to crosswalk these findings with your presentation of the MPN. Suggest discussing the significance of the co-occurring DNMT3A non-driver mutation with the MPN Specialist.
The complete answer to your questions will have to await the final results and review with the MPN Specialist. Meanwhile, here is some information that may help shed a little light.
ET - BM biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant left-shift of neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibers.
PV - Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size).
Pre-MF - Megakaryocytic proliferation and atypia, without reticulin fibrosis > grade 1c, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation and often decreased erythropoiesis
MF - Megakaryocyte proliferation and atypia accompanied by either reticulin and/or collagen fibrosis (grade 2 or 3)
There is a section of this presentation that talks a bit about what is being looked at in the BMB and other tests.
Your results are very similar to mine. I had a bmb in late January. The diagnosis favors ET but there is some bone marrow fibrosis. Your hematologist will likely provide clarification at your next meeting.Since my diagnosis I have had a blood clot. Now I am on hydroxyurea. It appears to be working with minimal side effects.
However, this diagnosis is the least of my worries. About a month ago I started noticing discomfort on the left side of my abdomen. Spleen is fine. I insisted on further testing and an ultrasound has revealed a large mass, probably ovarian with a spot on my liver. I met this week with an oncologist who thinks this may he benign and all tumor markers are negative for cancer. I have MRIs scheduled for this Sunday and extensive surgery will follow. I am hoping for the best, but my ET/prefibrotic mf is the least of my worries right now.
Mtnlife, very sorry to hear you are experiencing more issues. Wishing you a speedy recovery. Glad to hear lab markers negative. Sending you strength and healing.
Mtnlife - I so appreciate your response. And incredibly generous of you to spend time responding when you have so much going on yourself. Wishing you the best with your upcoming MRI and surgery - so much for you to go through.
As my mother has been telling me for years (and I am really starting to understand)...aging is not for the faint of heart. For most of us, managing our health as we get older is more an more of a challenge.
I am 58, diagnosed Aug 2022. I had BMB immediately as requested by physician at MD Anderson. Came back with few crossed fibers best described as ET. Jak2 positive. Then found an MPN Specialist near my home at Moffitt. Dr. Rami Komrokji. He explained based on my lab and bone marrow possibly PreFibrotic MF. Due to this, and my age, he recommended Besremi, interferon alpha. He stated one in five became Jak2 undetectable in the PV study. He explained why he doesn’t want other drugs taken. I felt he really cares. He is a leading researcher for MPN’s per google. I learned even though there is a small number who progress, some do. I decided to take the Besremi and hope to stop progression in my bone marrow as MF has much shorter expected life span. My numbers in two months fell from 717k to 476k. I am feeling much better too. Less inflammation, brain fog, less headaches. Ultimately less worry. I hope you are able to formulate a game plan you fully back when you meet with your doctor. I believe asking questions and finding the right Doc led to this path. Please share more about your journey. My B 12 level >5k and LDH elevated. LDH now WNL. Any information you gain and want to share, I would love to know. Some days I have read articles for hours and don’t exactly understand, but have learned so much from the people who share on this site. Best of Luck!
Thank you for the insight and information about your path. I have been making a list of all the questions I have related to to my BMB results. And these questions include adding interferon as a treatment option. I am fortunate to have a very good MPN specialist this past year that has always taken time to explain things and has indicated a partnership in deciding treatment, etc. Like you (and others), progression is my biggest concern, so if there is actually something that slows/stops the progression, I have to strongly consider it. Your comment about not understanding all the articles you read about MPNS resonate with me...often feels like a foreign language! I will provide an update once I connect with my doctor.
PS Jealous that you are in Florida! I am in Chicago...trying to figure out how to get out of here! 😀
LT55 - your BMB results were very similar to mine! I was diagnosed ET Jak2+ via consistently rising (over 5-6 years) platelet counts and the blood test. My MPN specialist said he always favors a BMB for a definitive diagnosis and to provide a base line for potential future comparison.
My results were as follows: Final Diagnosis - Myeloproliferative Neoplasma, Essential Thrombocythemia - ? Pre-MF
My gene sequencing had shown only the Jak2 mutaiton (but at 40% allele burden) and very minimal TET2 (2-4%).
The question mark in front of the Pre-MF of course threw me for a loop. I had a very long discussion with my MPN specialist (one of the best) as to why there was a question around pre-MF. He stated that the overall morphology supported an ET diagnosis but specific results warranted additional analysis: Hypocellularity (80%) - this was a flashing red light according to him - the expected level of cellularity roughly corresponds to the age of the patient (not a hard rule but good rule of thumb) - at 50 years old, mine was very elevated; the relatively high allele burden for ET (he cited a recent study that an allele burden >50% favored a diagnosis of pre-MF while ET "in general" was more likely to be 18-30%) . There were blast cells up to 3% (none in blood) and plasma cells at 5% (normally plasma cells make up 2-3% of the cells in bone marrow). On the positive side of things - M:E ratio was fine (at 3:2); also Special stain for reticulin did not highlight increased reticulin fibrosis and no tight megakaryocytic clusters were identified, which favored ET.
In our long discussion, he stated that he thinks of MPNs as being on a continuum and some patients present initially with characteristics of more than one MPN (ET and PV or ET and pre-MF for example). Over time some patients'MPNs can morph into another (ET to PV) or progress from ET to MF. He said that each disease, and its potential course, is as individual as each of us. In my case the important question was, would there be a difference in treatment plans or goals if we classified this as ET or ET with a possible pre-MF connection? In general - no. Although, it did give me the push I needed to demand to be on the interferons as soon as possible as they are the only medication, currently, that have the possibility of potentially slowing progression (or perhaps for a select few even remission). So officially, my diagnosis remained ET but we agreed to start Peg and to have increased allele burden monitoring. I am also likely to have another BMB sometime toward the end of this year (3 years after my initial BMB and 18 months after being on Peg) - so we'll see if there is any difference, positive or negative, at that time.
The great news is that you are under the care of an MPN specialist and we now have treatment options. Best of Luck!
Solyesh, I am grateful for your response and appreciate you sharing the detailed explanation of your situation and what the various BMB findings mean in your case and in general. Beyond helpful. I definitely think a discussion with my doctor about interferons is warranted.
MPNs are so complex. I don’t think I realized just how complex until the last year. And while so many similarities across all of our situations, each so individual as you point out.
Your situation is similar to mine as well, and Hunter has provided some excellent information and guidance, as he so often does. My Dx of PrePMF was apparently based, in part, on elevated LDH and my additional mutations (SRSF2 and del(20Q)).
I have been on 45mcg of Pegasys for almost 2 years during which time my frequency has been decreased from weekly to every 2 weeks. At 74, I am feeling well and showing no signs of progression.
A bit of caution on diagnoses. I was originally diagnosed with prePMF after a BMB and genetic test (JAK2). But reading the WHO criteria, it wasn't clear to me how the BMB results put me in the prePMF camp. At the time my MPN specialist moved to a different hospital, and luckily I have a choice of several specialists in my city.
Long story short, I discussed with my new specialist, who agreed with me that the results to him did not necessarily show prePMF based on the WHO criteria. He asked me to send my BMB slides etc. to his hospital where he had a different pathologist re-analyze the same data from the BMB. That pathologist suggested the data favors ET.
I thought about posting a thread with the two pathologist summaries as an example of how data can have different interpretations depending on the individual.
Thank you for your response. MPNs certainly are not straight-forward for sure. I have a virtual appointment set up with my specialist...looking forward to his perspective.
UPDATE: I was able to connect with my MPN specialist. He was able to answer my questions. He believes that the BMB does favor ET. His rationale is that 10-years post-diagnosis, there is no scarring or inefficiencies in the marrow (good!). There is also an absence of symptoms that would typically support pre-fibrotic MF or MF (enlarged spleen, night sweats, rising white cell counts, increased hemoglobin, etc.). I asked specifically about the DNMT3A mutation. He did not think this was a high-risk mutation in ET, and that it would not be a risk factor of a condition that was clearly expected to progress.
I asked if some of the findings (increased cellularity, increased M:E ratio, variable megakaryocyte morphology) meant that I could have a higher risk ET (i.e., more likely to progress). He didn’t think this was the case. Again, he was very focused on the ten years and no fibrosis as being encouraging.
The plan will be to continue to observe. He did not believe there was any reason to consider treatment options at this time given our previously discussed objectives. If symptoms develop, or other triggers (e.g., blood clot), treatment will be considered. Treatment options also to be considered at age 60 (which sadly is not that far off). I asked about a future BMB (e.g., value in another one in 2-5 years) – he didn’t think so unless there was an obvious change.
Will see him in six months and continue the conversation. Thanks again to all for your support.
That does sound like good news and very reassuring. It also sounds like you have a good plan in place. When it is time to consider cytoreductive treatment, you will have multiple options. Perhaps even more options than if you started today. Given your concerns, discussion of the treatment options most likely to decrease risk of progression would make sense.
Regarding passing age 60, I did that 7 years ago. It is great! Best to enjoy whatever age you are as it is subject to change in only one direction. There are many reasons to enjoy turning 60. Here are 60 of them from the Huffington Post. huffpost.com/entry/turning-...
1. You can enjoy the freedom to dress down when you want.
2. You know who your real friends are -- and they all weren't college roommates.
3. You truly understand other people and have gained a real appreciation for all types of personalities.
4. You know what really matters and have stopped striving for needless goals.
5. You know high heels were designed by a misogynist and just don't wear them.
6. You have weathered marital storms and your relationship is stronger because of it.
7. You are okay spending time alone; in fact, you prefer it sometimes.
8. You know it's perfectly fine staying home on a Saturday night.
9. You know the value of sleep and are okay being the first to leave the party to go home and get some.
10. You can laugh off jerks instead of getting enraged by them.
11. You know that diet is a lifestyle, not a temporary restriction on what you eat.
12. You understand that garments like Spanx are cruel and unnecessary additions to your life.
13. You aren't afraid to stop reading the book everyone is talking about after 10 pages, even if "Gray" is in the title.
14. You know that black isn't just a color; it's the only color.
15. You know that you don't have to sit through "Girls" just because everyone else does; after all, no one on the show is anything like your daughter.
16. You know who you are and that there's still time to change direction.
17. You have been known to work in the garden on Sundays without a bra -- and it's fine.
18. You know enough to stay out of the sun without sunblock on.
19. You carry a shade umbrella in your trunk and aren't afraid to use it.
20. You no longer worry about where your hemline should be and instead wear what's comfortable.
1. You sit down at concerts and no one cares.
22. You know the excitement of an office romance and
23. You know better than to engage in one.
24. You know that when you color your hair, you do it for yourself and not anyone else.
25. You know that sex really CAN be better as you grow older.
26. You have learned how to weed out the users, the time-sucks and the emotionally needy from your life.
27. You know that relationships trump money.
28. And you know that good health trumps everything.
29. You take care of yourself because, as you know, if you don't, who will?
30. You appreciate a good laugh and seek them out.
31. You don't have to pretend to like horrible music.
32. You know that people are more important than things and you now prefer to collect good people in your life.
33. You know that work may feel important at times, but it's never as important as your family.
34. You know that work is best when you care passionately about what you do.
35. You can go gray -- and know that it looks spectacular.
36. You no longer take bucket lists seriously because you live every day fully.
37. You don't need to be told to disconnect in order to connect.
38. You know that good fences make good neighbors, but so do groceries delivered when the neighbor is sick.
39. You know when you need a nap and make the time to take one.
40. You have lived through some amazing times -- the first man on the moon just to name one -- that younger people have not.
41. You can tolerate the occasional check-stiffer, chronically late person -- once.
42. You just have to get out on the dance floor to impress people.
43. You are finally getting carded (AARP carded) again.
44. You get to see your kids turn into really interesting adults.
45. You still use the phone to talk to friends.
46. You really "get" that a successful marriage takes work but understand that it's worth it.
47. You totally get the value of having kind people in your life.
48. You can admit you were wrong about not trusting anyone over 30.
49. You understand that gossiping about people lessens you, not them.
50. You know that traveling broadens you and is worth doing as often as you can.
51. You are happy to just wear sweatpants and know you look best when you feel comfortable.
52. You have more time to enjoy life since you probably don't need as much sleep as you did 20 years ago.
53. You understand that stores whose clerks know the merchandise is where you will spend your money.
54. You accept that some things are simply outside your control.
55. You understand that being a good listener may be better than being a good talker.
56. You know the value of anyone who makes things easier for you.
57. You have amassed a rich diversity of life experiences to draw on when facing a challenge.
58. You know that elders aren't the only ones you can learn from; younger people have a perspective worth being open to.
59. You are okay following rules but aren't too old to try and change a few of them.
60. You realize beyond a shadow of a doubt that turning 60 is just a number anyway, so why stress?
Why stress indeed?
All of us 60+ types are like a fine wine or great whiskey - wonderfully aged - not old.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Spleen slightly enlarged on the upper side of normal. UPDATE on results.
Does Interferon affect BMB results?
MPN-U or MPN Unclassifiable
Is a BMB always the only way to diagnose an MPN?
