Hello everyone. I am trinigirl from the Caribbean and have posted about my ET diagnosis before. I had problems with my doctor and his knowledge of this illness and was very unhappy with him. I have not posted for a while because I was under the weather. I changed my hematologist as was advised to. I am very satisfied with this new one. He ordered a bone marrow biopsy as I had never had one done. The results are very interesting and baffling to the doctor and pathologist. My specimen had to be shipped to the US and the results show no signs of ET as was diagnosed in 2017 and also I am JAK2 negative now whereas I was positive in 2017. He said from all the research he checked it is impossible to have this results just being on HU. It would seem as a total molecular remission which is strange because I am not on any suppression drugs like Jakafi. He has cut back on my HU which is the cause of my adverse blood counts. My white and red are all very low. Hoping to see an improvement. Has anyone gone through something like this? Would love to know. I have also just received my 2nd booster of the vaccine. Hope everyone is doing well. Stay safe. Just to conclude that my platelets counts are very good, 280. It has never gone out of wack since starting HU 5 years ago.
BONE MARROW BIOPSY: Hello everyone. I am trinigirl... - MPN Voice
BONE MARROW BIOPSY
In studies I've seen and posted, HU often reduces Jak2, but only in the 1st year or so and not to zero.
The report below shows that HU can reduce allele even at 24 months. But not to zero.
Do you know what your allele Burden % (AB) was in 2017? It seems your 1st AB was from blood and the recent one was from marrow. Is that right? Blood and BMB can sometimes give different results (mine differed by 5%) and if your 2017 Jak2+ result had a very low AB this difference could be relevant.
It seems your recent BMB shows no marrow defects, is that correct? There are specific physical features they look for to Dx ET (and other MPNs).
When was your HU cut? Any CBCs since?
In any case, a pleasant mystery.
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ncbi.nlm.nih.gov/pmc/articl...
<<JAK2 VAF decreased in 94% of the patients treated with IFNα and in 75% treated with HU >>
Hello EPguy. Thank you for the response. I lookedat the report but did not see anything about the AB to which you refer. Yes my first specimen in 2017 was blood and in April 2022 it was BMB. I do not have a copy of the BMB report with me at this time. I was told by tge doctor that the specimen shows no defect. He is still investigating it by checking sll the researches done around the globe to come up with an answer.
My HU was cut after my visit to the doctor last week. I am to see him in 5 weeks when we will do CBC. I will keep you posted as to the findings. Hope you are doing good as you seem to have great knowledge of this illness. Thanks again for the information. I will check out the link you sent.
Hi Trinigirl, sounds like you might benefit from a visit to a MPN specialist. Maybe you could visit a specialist at Moffitt Cancer Center in Tampa Fla. (South Florida) or maybe one in Miami. I understand that they have some excellent MPN specialists at that facility (Moffitt). I don't know where you are but it might not be too long of a flight.Best to you in getting the answers you need.
It seems your Dr is smart and inquisitive. But as Meatloaf says, an MPN specialist is worth finding. As a minimum your Dr should have contacted one in his research. Did you get your USA specialist visit in January? Your Dr should be working with that specialist if you did.
You should ask whether your AB is available from the 2017 test. It can vary from 0 to 100%; ET tends to the lower end of the range, with exceptions. It's possible it was very low; some people can be Jak2 + at a low % and not have actual MPN.
I saw your old post that you had PLT of 424. Is that about the highest you've been? That is safely below the max 450 that is currently most common. Some Drs even consider 600 to be ok. And as you can see in posts, there are various non-MPN reasons for increased PLT: the "essential" in ET means the MPN is the essential reason for the abnormalities.
my.clevelandclinic.org/heal...
<<There are two types of thrombocytosis: primary and secondary>>
It's curious whether your ever actually had MPN, the specialist must have had some insight. Did they mention possibility you have secondary thrombocytosis?
Hi EPguy. I am amazed at the knowledge you have of these MPN's. Yes my new Hem is very smart and knowledgeable, too. I would not surprise me if he has not already consulted with a specialist. My highest platelet level was 900+ but it is now just over 260. I did see an MPN specialist in Fĺ who suggested the BMB and I returned home to have it done. My former Hem refused to do it which made me switch even faster. I am so happy that I did it. No mention was made of secondary thrombrocytosis. Happy for all the information and suggestion. Will keep you posted . Thanks again
Here is another report we've seen recently. It's mostly about how good Besremi was, but there is this part buried in there:
nature.com/articles/s41375-...
<<in the control arm, only 1 patient (1.4%) achieved an allele burden <1% at 60 months >>
Most the control arm was HU, so this person likely was on HU but not assured. Assuming your AB was higher than 1% at the start, you could be like that "only 1" person. You are right near that same 60 months.
Hi EPguy. I am happy for the response. Wish I could understand all those reports like you can. I get some of it, some I have to research and some I lack the knowledge. Can I ask what is your prrofession? Hope you are not offended. I am surely reafong line by line. I am really being informed. Much appreciated. Will check what my readings were.
I'm glad to help.
Those reports have a lot of things on other subjects which complicates looking at them. For the part that matters here it's just to know that a Jak2 reduction is rare but possible without interferon (INF, which is currently the main way it gets reduced for many) But I don't know if these patients had no MPN findings in their marrow, that is likely even more unusual to have that disappear since some studies, for INF, have shown AB and marrow don't necessarily improve together.
I'm surprised your Dr did not at least tell you why secondary thrombocytosis was ruled out. Esp if your starting AB was really low, (we don't know yet) I would think they'd look there. My 1st Dr considered it an option (since it's usually a nicer answer) till my abnormal BMB and 15-20% AB ruled it out. But if your AB was not low, then it's reasonable they concluded MPN.
I'm an inventor, engineer artist and some other such things. I have much curiosity to learn when I need to care, and I care a lot these days about MPN. This forum is a great place to learn and to share the learnings.
Another member you might want to check out his postings is Hunter5582 ("Hunter"). He is extra knowledgeable and has discussed some of these things also.
EPguy, really appreciate all the explanations. When next I visit my Dr I am going with confidence and questions, thanks to you and this forum. Will do some more reading so I can fully understand the scenario of what might be happening with me. Take care and hope all is under control on your side.
Thank you for providing this link to the article on genomic profiling. My main interest is because I had the DNMT3A mutation initially at my diagnosis 4+ years ago. I am looking for some evidence of it's effect on progression and overall survival. Do you have a link to any articles that have found the association of this mutation and progression or survival?It is interesting that 16% of patients had this mutation at baseline and also that it is the most common treatment emergent mutation during treatment with Inf alpha. I think it said 61% of the treatment emergent mutations were dnmt3a and were in those treated with Inf alpha, while the most common treatment emergent mutation with HU was TP53 which I believe is a bad one.
Since Inf has been used for at least 30 years in Europe for the treatment of MPN, I would think that someone somewhere has published material on progression and survival with the treatment of Interferons over an extended period. I have not been able to find any such literature, have you seen any info on progression or survival with the very long term use of interferons since they have been used for decades in EU. Something along the lines of 15 or 20 years or longer results?? The longest studies I have seen have been for 5 to 7.5 years.
Thanks for posting and thanks for all your contributions to this forum, very informative.
Best to you.
I think you may have intended this reply to be in the thread:
healthunlocked.com/mpnvoice...
For your 2nd part question, I posted last year one that is right on the subject. It does not go into genetic details since our mutations were not even known 20 years ago. But it is compelling. My Dr minimized it since it was retrospective, but I think he's more on board now with the long term INF idea. I contacted one of the authors about the retro part and he said they worked hard to correct for that. I think this report is one reason for INF revival:
healthunlocked.com/mpnvoice...
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For DNMT3A:
The best relevant connection of DNMT3A to prognosis was its correlation to lower odds of CHR, and CHR generally is better for our outcome. One weakness of the study was its short duration, 24 months. So they could not look well for progression or INF's best benefits.
They do note the HU connection to TP53 in their study but also note that HU pts tended to be older and TP53 is more common with age. But they cite other chemo agents are known to affect TP53.
A reference in this report has as below, but it's 2014 vintage and small n.
<<The number of individual patients with mutations in DNMT3A, ASXL1, EZH2, or IDH1 was low, and when combined as a group, these patients showed no significant differences in the clinical course>>
But for TP53 <<somatic mutations with loss of heterozygosity in TP53 were strongly associated with leukemic transformation>>
ashpublications.org/blood/a...
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In another citation TP53 is esp bad as you note:
<<As in patients with other blood cancers with TP53 mutations, these patients have a dismal prognosis with a high risk of transformation to acute myeloid leukemia, (hazard ratio vs. the JAK2-heterozygous subgroup, 15.5>>
I think heterozy in this context is the change specifically of TP53 to homozygous, not the Jak2 status discussed in other posts.
nejm.org/doi/full/10.1056/N...
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Thank you for posting this info. Especially the link to the predictions for MF free survival and overall survival. That is the info I was looking for to take with me next month when I see my mpn specialist to discuss switching to one of the interferons. My counts are well controlled on HU so far. I will likely leave the decision to him.
It all sounds like good news to me. Is your haematologist considering taking you completely off hydroxy?
Hi Hopetohelp. I really do hope it is good news. Taking me off HU will depending on the outcome of the results and my future blood reports. I know my Dr is doing all he has to do to interpret this results. Thanks for the response.
BMB (Bone Marrow Biopsy) 
Bone marrow biopsy 
Bone marrow biopsy done
Bone marrow result - cryptic
Bone Marrow Biopsy
