pre MF what to expect

[Fjdjdjdjd]

I was recently told than the BMB indicated that I have pre MF rather than ET. I have grade 1 fibrosis. What can i expect to happen here? Does anyone else have pre MF, are you symptomatic?

[Solyesh]

Which indicators led to the pre-MF diagnosis? This had been an ongoing discussion with my MPN specialist. Given my relatively high Jak2 allele burden (40%) for ET; persistent leukocytosis (high WBC - minor criteria) ; minimal scarring (between 0 and 1) and hypocellularity (up to 80%) - I had questioned whether we are dealing with pre-MF as opposed to ET. In fact on my BMB they also questioned whether they were dealing with pre-MF vs ET. They officially decided ET.

The WHO came out with new diagnostic criteria relatively recently (2016) in an effort to better identify pre-MF cases being masked as ET. Here are some background papers on the challenges and importance around classification:

nature.com/articles/s41408-...

onlinelibrary.wiley.com/doi...

mpnforum.com/twoworlds/

My MPN specialist agreed with me that I am likely a borderline case. In his opinion, he believes that most MPNs sit on a spectrum and the hard differences between the presentations are not clear cut (especially within the same driver mutation). He has patients classified as PV with mainly ET characteristics and some ET patients which might be pre-MF.

The question for me is would treatment and approach be different if I was classified as pre-MF vs ET (or late ET)? In my particular case - no as I am already taking Peg. I had been watch and wait (asymptomatic) until a spike in platelets led me to begin cytoreduction. Started on hydroxyurea but did not tolerate well and pushed to switch to interferons. I also pushed for Peg/interferon as it is the only, currently available, medicine which might help arrest or reverse disease progression.

My MPN specialist did state that a pre-MF diagnosis (vs ET) might have pushed him to recommend starting me on an interferon despite me being asymptomatic and low-risk (age; no history of thrombotic events; etc.) as opposed to just wantch and wait (baby aspirin) - "luckily?" the spike in platelets (from 900 to 1,400 with minor bleeding at the gums) led us down the path to medicine anyway...

I am completely asymptomatic to date (was prior to medicine as well). Have you had a complete gene panel to see if you have any additional mutations (in addition to the key driver (Jak2; CALR)? This can be key for treatment planning as well. In my last discussion with the doctor 3 weeks ago when I pushed on the pre-MF vs ET diagnosis - we agreed to another gene panel and BMB in a year to see if the interferon has changed anything.

I know it can definitely feel a lot scarier to consider a pre-MF diagnosis vs ET but, in my opinion, additional info/data always best - to help make most informed decisions moving forward..also hopefully you are/remain mainly symptom free as for me quality of life is also paramount.

All the best!

[Fjdjdjdjd in reply to Solyesh]

Thanks - I'm starting to come to terms with the idea that my diagnosis is going to flip-flop flop and I just need to be ok with that, and just say for now I have an MPN.

You are right that the key thing is if I have scarring and it's progressing should I be on interferon as I'm 33 and when they tell me things like 10 years should be fine, that's not really fine. If interferon could block Jak2 maybe it's worth it, but I'm waiting for my referral to Guys as I don't have a specific MPN specialist right now.

pre-MF is a lot scarier to me after I had come to terms with ET. I seem to not tick lots of boxes, apparently, I have an undersized spleen (though I am very short). . Jak2 is low but platelets have been high for 7 years and the other blood are borderline normal. I think I have symptoms but have been generally ignored and marked as asymptomatic. But I have feinted a few times and get aura migraines.

[Solyesh in reply to Fjdjdjdjd]

Agree that pre-MF definitely feels scarier than ET but most important is how you are feeling and the path forward. You will be in some of the best hands in the world for MPNs with Guys (push to make sure referral happens sooner than later)!

Best

[Threelions in reply to Fjdjdjdjd]

interesting you mention the aura migraines. I suffered massively from awful aura migraines for a couple of years pre diagnosis. Ever since I started peg interferon the migraines disappeared completely. I’m not as young as you (was about 49 when suffering the aura migraines & diagnosed with ET at 51/52-following a TIA) but still relatively young in the overall scheme of things. If I was you I’d really chase up the referral to Prof Harrison & her team at Guys. She is an angel to deal with and one of (if not the) best MPN expert in the UK. I was contacted by Guys a fortnight after being referred.

Good Luck,

Mark

[EssThro in reply to Fjdjdjdjd]

Thanks for raising this question, Fj, and to those who have provided great comments. I have a low JAK2 burden, and was initially diagnosed with ET. Later, it was changed to Pre-PMF, largely due to my mutation profile which includes the presence of SRSF2 and a more benign mutation which are both common in MF and quite rare in ET. Having low allele burden and 0-1 fibrosis, my MPN specialist is saying that my prognosis is similar to a person with ET, especially because I was put on Pegasys right away. That has reduced my mild migraines and other symptoms. I think that having SRSF2 is a wildcard, but my future looks very bright now. As in some comments, Pegasys seems to be getting a great reputation for treatment of ET and Pre-PMF.

Good luck to you!

[EPguy in reply to EssThro]

Interesting that your Dx is largely based on two combined non-driver mutations. Do you know what the 2nd one is?

[EssThro in reply to EPguy]

Yes, I do. I seem to be in a mood today, and do not want to share more on the forum. Suffice it to say that the diagnosis is based on the totality of my symptoms and testing, including an elevated LDH which has come down into the normal range.

[Threelions]

Hi, Following my BMB around a year ago I was told I had grade 1 fibrosis. Was told by my team at Guys that this was totally acceptable & in line with my ET diagnosis some 2 years prior to the BMB. Essentially I was told there was nothing to worry about.

The way I look at it (with my limited knowledge) is that even if grade 1 fibrosis is pre MF then I’m not really in any different situation than if I “just” had ET bearing in mind anyone with ET “could” technically develop MF. Moreover my treatment (interferon) wouldn’t necessarily change if it was decided I was pre MF.

All that said I wonder if monitoring might be different if grade 1 fibrosis was, in fact, definitely pre MF.

[Fjdjdjdjd in reply to Threelions]

That's interesting. The Haematologist at Hemel, after a very long time (5 months) contacted me and said he thinks following the BMB and the fibrosis it wasn't looking like ET but pre-MF because he wouldn't expect that level of fibrosis in ET at 33. I'm now being referred to Guys for a second opinion, though I have little faith in how long this will take! I think the team at Hemel are a little overwhelmed/out of their depth as there seem to be two consultants only and one of them is a locum. I'm not on interferon at the moment as I think they basically want Guys to make the calls. I was only 6 months into the ET diagnosis and struggling to get my head around it when it changes to pre-MF which feels much bigger.

[Emmyroos in reply to Fjdjdjdjd]

I had the same "upgrade" to my original ET diagnosis after my first BMB = Mild grade 1 fibrosis. My Dx changed to pre-MF also. I see an excellent MPN specialist and she has reassured me that with treatment like interferon, I can expect a fairly typical lifespan and quality (especially catching it at grade 1) and the management of the disease will be more like an ET diagnosis. I was also diagnosed in my 30's. After the change to pre-MF, my doc immediately started me on Pegasys. There is evidence the Peg not only will slow the progression of the disease overall but has the potential to reverse the existing scarring that has occurred in the bone marrow.

Also my doctor made sure I understood there is a distinct difference in pre-MF and primary MF. Just be aware of that... a lot of the information on a quick google search is for primary MF (and that is VERY outdated btw!!).

I know it probably feels like a big jump from ET and it can feel very worrying. Try not to stress too much (like I did!), and just be aware there are very effective medications out there for us now. And Grade 1 is early! Like any disease catching it and treating it early is key.

[Fjdjdjdjd in reply to Emmyroos]

Thanks! It took them 5 months to tell me the outcome of my BMB so i'm hoping it wont take that long to get referred and put on interferon if I need it.

[Emmyroos in reply to Fjdjdjdjd]

FIVE months is completely unacceptable. You deserve timely and excellent care. I would recommend you do everything in your power to get in to an ACTUAL MPN specialist so you no longer get caught up in between your GP and standard hematologist (which neither fully understand the condition in order to treat it most effectively). I think I read you were being seen by one in Feb?? (If so, that's great! ) I'm on Pegasys now and yes it was a tough few months to start but I feel like I got my energy and life back after being on it for a year. I also just got my bloods back in order for the first time in years. Good luck and feel free to reach out to us for support.

[Fjdjdjdjd in reply to Emmyroos]

cc of the letter asking for the MPN specialist to review my case just came so fingers crossed. I have 0 confidence the right process has been followed

[Eloise70]

Hello, I have received pre fibrosis diagnosis after 2nd BMB. I will start on Hydrea soon. My main symptoms currently are swollen, red fingers (itchy, too) apparently this is due to sludgy blood which coagulates in capillaries. Dr says hydrea may relieve this condition... we will see! Otherwise I feel much the same tho I must admit I am less enthusiastic about most things and don't feel up to doing much if it requires an effort. I wish you well.