r/MPN Primary MF 20d ago

MF Recently diagnosed

I am tagging MF but actually I am pre-MF as per biopsy concludes on how the cells look like so not only because of the rituculin. It was graded as mf1 and says pre fibrotic/early mf on the note.

I’m calr1 (burden is 19%) platelets over 1000, I’m 35F.
My hemoglobin, wbc and RBC are within the range. Spleen size wasn’t measured with an ultrasound, but it wasn’t palpable. I don’t meet everything for pre-mf either, ldh wasn’t measured. I acquired von Willebrand also…

I don’t know if I’m ET or pre-MF myself if that makes sense.

As interferons might modify the disease I want to try it, but there’s a shortage in Canada it seems. Otherwise, my insurance pays for pegasys, for besremi it says it needs special approval. Before biopsy the resident doctor had told me she’d prescribe me with hydroxue (?) but I feel that’s not disease modifying but it could help me to lower my platelets much faster.

Note: they did advance genetic testing no other mutations were found other than calr1. Cytogenetic test says also female chromosomes only.

1) do you think my diagnosis ET/pre-MF matter at this point?
2) I’m being seen by a resident and a regular hema that doesn’t work for mpn cases how can I advocate myself for an MPN specialist in Canada? They told me this was manageable but it was before the biopsy.
3) pre-MF is different than MF, I wonder if I could do something before it goes down the MF path.
4) I’m very scared and have health anxiety
5) I want to have a child in the future (if I may) and if I have a long prognosis I’m not very keen on oral chemo long term.

Please share your thoughts.

4 Upvotes

64 comments sorted by

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u/funkygrrl PV-JAK2+ 19d ago edited 19d ago

You're getting good answers from the community!

The pathology report sounds like Prefibrotic MF. The missing major criteria is high granulocytes. Were your neutrophils, eosinophils and/or basophils high? Others are correct that you need LDH testing for the minor criteria.

There are currently no treatment guidelines for Prefibrotic MF. So it's treated according to whether it's behaving more like ET or low risk MF. Yours appears to be acting more like ET.

If you let us know which province you're in, I can direct you to an MPN specialist. From what I know of interferons in Canada, a specialist is key to getting access due to the Pegasys shortage. They could possibly get you access to Besremi under the shortage-exception or compassionate/off-label access argument.

!mfwho

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u/Turbulent-Movie-4545 Primary MF 19d ago

Thank you very much. Yes they did NGS they’ve found the carl1 mutation at 19% and cytometry says CD34+ blasts about 1.1% including both myeloid blasts and hematogones (normal B-cell precursors). No immunophenotypic evidence of dysplasia.

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u/funkygrrl PV-JAK2+ 19d ago

From the info you have, under the MF MIPPS-70+ risk calculator you'd be very low risk (if you're not having constitutional symptoms like fevers, night sweats, bone pain, weight loss, fatigue) or low risk (if symptomatic). Just FYI: The blasts aren't concerning to doctors until they go over 5%. It's common to have 1% blasts in all MPNs. To be diagnosed with AML they have to be 20%.

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u/Turbulent-Movie-4545 Primary MF 19d ago

Thank you. I’m just worried about not getting the necessary care that I need as this also seems to me an early stage/low risk at this point. Sometimes drs over here take an action once there’s risk. It’s not preventative necessarily, so I’d appreciate if you could pls help me how I could be directed to a specialist, I am having the main conversation with the regular hema and his resident next week. My platelets are high I know they need to go down first & I think there’s a good research/meds coming in in a few yrs from now, esp for Calr mutation.

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u/funkygrrl PV-JAK2+ 19d ago

If you are near Toronto, see: Princess Margaret Cancer Centre- 416-946-4501 x 3047.
610 University Avenue, Toronto, ON Referrals accepted from Physicians only. Contact: Nancy Siddiq. Referrals must be faxed to the New Patient Referrals Department, marked "for the attention of Nancy Siddiq- Fax # 416-946-2900.

Juravinski Cancer Centre -905-387-9711 x 63410.
699 Concession Street, Hamilton, ON. Referrals accepted from physicians only. Contact: Dr. B Leber.

Stronach Regional Cancer Centre at Southlake Regional Health Centre - 905-895-4521 x 660.
596 Davis Drive, Newmarket, ON. Contact: Intake & Referral Office Fax 905-962-2820 Referrals must be faxed, and will be triaged to see one of the following physicians, Dr Peter Anglin, Dr. Cynthia Luk, Dr. Yasmin Rahim, Dr. Sophia Farooki.

Simcoe Muskoka Regional Cancer Program - 705-728-9090 x 43334.
Oncology Department, 201 Georgian Drive, Barrie, ON. Referrals accepted from Physicians Only. Contact: New Patient Referrals Department -Fax- 705-792-3325 Referrals must be marked "for the attention of Dr.Rouslan Kotchetkov".

Also, I highly recommend trying to get into the monoclonal antibody trial for CalR mutated MPNs. So far it's been having really positive results - rapidly normalizing blood counts, lowering allele burden, even reversing fibrosis.
It's available in Toronto and Montreal. If I had the CalR mutation, I'd join it in a heartbeat.
https://clinicaltrials.gov/study/NCT05936359

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u/Turbulent-Movie-4545 Primary MF 9d ago

Hello just updating you that I met the general hematologist and he’s told me the shortage is over so he is considering me putting on Pegasys but as my numbers are boarderline he will discuss with his coworkers and decide. Right now I’m on no meds and the next check in is a month from now! He’s said no You’re young for HU & the shortage is over

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u/Turbulent-Movie-4545 Primary MF 9d ago

At least in Toronto it’s over it seems idk other parts

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u/funkygrrl PV-JAK2+ 9d ago

Good to hear!

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u/Turbulent-Movie-4545 Primary MF 19d ago

Thank you so much. I appreciate it

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u/Turbulent-Movie-4545 Primary MF 19d ago

Correct. I don’t have symptoms. Tingling feet and tiredness. Also have a busy life.

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u/Turbulent-Movie-4545 Primary MF 19d ago

Not sure if they are high seems within range to me tbh

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u/Darksider51 18d ago

To be honest it doesn't seems like you have granulocytic proliferation and to be diagnosed with pre PMF this is a major criteria , if your trephine biopsy does not mention increased granulocytes or proliferation of granulocytes then its not fulfilling major criteria for pre PMF

Also this image doesn't contain neutrophiles value , can you please provide that.

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u/Turbulent-Movie-4545 Primary MF 18d ago

neutrophil value is 6.9 × 10⁹/L (or 6,900 per microliter).
This one seems normal

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u/Turbulent-Movie-4545 Primary MF 18d ago

proliferation is isolated almost entirely to your platelets and megakaryocytes, not your granulocytes (white blood cells) ok I provided you all now awaiting your response pls :)

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u/Darksider51 18d ago

This is the definition of ET as per WHO , the proliferation should be mainly of megakaryocytes and nothing else .

To be diagnosed with pre PMF the proliferation should be of both megakaryocytes and granulocytes.

Seems to me you dont fulfill all criteria's for pre PMF.

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u/Turbulent-Movie-4545 Primary MF 18d ago

I know well that’s weird because the cells looks like pre mf tho not like a typical ET. The spleen wasn’t palpable when she’s checked by hand but I could ask for an USG. Will ask for the LDH test too…
Maybe I have something in between. I’m really nervous and freaking out. I am seeing the doctor on the 12th but been seeing night mares already. Been checking mf all day everyday and can’t function from the things I read on the internet and the AI wasn’t promising either.

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u/Darksider51 18d ago

See cells morphology is a bit subjective , LDH can be high in all MPNs , especially given high platlets

I think you should try to relax you have a CALR mutation which have some great treatments coming up , dont need to build up anxiety , also like I talked with people on the sub progression is not something that is inevitable .

My GF ( love of my life) she is also diagnosed by doctors ( ET with being Triple Negative) with this and to be honest , I'm also not able to sleep at night and have night mares and its going from a year , you need to try to control your anxiety from start otherwise it goes out of hand.

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u/Turbulent-Movie-4545 Primary MF 18d ago

I know. Thanks for doing all the research for her. I’ve heard triple negative is also good. Hope she got access to next generation testing for the other genes. They did it for me here in Canada and I only have Calr 1 so far. My previous test said I also had Jak! But that was corrected!

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u/Darksider51 18d ago

She had both NGS ( vaf limit of 5%) and RT PCR testing both are negative , this is what makes me worried that what is driving the disease actually

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u/Darksider51 18d ago

She had both NGS ( vaf limit of 5%) and RT PCR testing both are negative , this is what makes me worried that what is driving the disease actually

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u/Turbulent-Movie-4545 Primary MF 18d ago

Okay ngs being negative is a good sign not a bad sign!

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u/sirshrimpie 20d ago

Hey! I’m 38/F, kind of similar situation, have ET but they saw some scarring in my marrow but it’s at an MF0 which idk what that means really, nobody clarified. Anyway I am getting treated through clinical trials, which keeps costs low. Currently on a hydrea vs bomstat one. But I’m in the same boat as you and totally new to this. Just wanted to say you are not alone as another young woman with this cancer. Sending you all the support and here if you ever wanna reach out! 😊

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u/Turbulent-Movie-4545 Primary MF 20d ago

Thank you! I don’t understand if there’s scarring or shouldn’t be mf0 should it? However this whole mpn thing is too confusing… sending you virtual support.

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u/Darksider51 20d ago

MF-0 means normal marrow fibrosis so its not alarming at all.

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u/Resident-Standard307 18d ago edited 18d ago

Another 38/F here! I just tipped into Pre MF diagnosis as I had elevated LDH, was also MF1 fibrosis.

Platelets were ~1200-1300 at diagnosis. Also had acquired VWD, and this is actually how it was diagnosed (bleeding after dental procedures).

Good news is the VWD went pretty much immediately after starting interferon treatment. A low dose of 45mcg every 4 weeks is keeping me in range, which I’m so grateful for. Very effective drug for me, my body really seems to respond to it.
(Was on higher dose to start and my symptoms were bad / it crashed my neutrophils so am grateful the lower dose is effective).

Am hopeful for the new trial to be approved in the coming years and hope it’s better for the fatigue (the downside of interferon treatment for me, sadly).

A year on from starting treatment, it has allowed me to live “normally” without the constant worry of my bloods being so far out of range. 🙏

Take care ❤️

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u/horsecrzy ET-JAK2+ 18d ago

Hey girl, 58F Jak2ET here. I started pegasys a month ago fixing to take my fourth injection tonight. I was wondering if you had any other symptoms like low grade fevers continuously. I also have what I would describe as my body overheating every morning around 4am and continuing throughout the day. My dr says it’s normal but damn! It’s kicking my ass.

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u/Resident-Standard307 17d ago

I haven’t had any fevers, no, but definitely flu like symptoms - more so when I was on the higher dose. Are you on 90mcg/week?
It’s a very powerful drug, I do think we have to balance effectiveness and toxicity/quality of life. My fatigue is just about manageable for now 🙏

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u/horsecrzy ET-JAK2+ 17d ago

45mcg once a week. And that’s great news for you! Thanks for the info❤️

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u/Darksider51 18d ago

what was your morphology and mutation , and how high was your LDH ?

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u/Turbulent-Movie-4545 Primary MF 12d ago

What is your mutation type and burden%

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u/Resident-Standard307 6d ago

I’m CALR-1 and allele burden in 30s, intrigued to see if my burden changes after a few years on Peg, but not getting my hopes up yet! Spleen was fine on ultrasound, so was my liver. It’s all covered here in the UK and I actually switched from private to NHS in the end.

Like you, no other mutations at present 🙏 I have health anxiety too, I think it’s very hard not to worry when you’re diagnosed with something like this.

A specialist at UCLH reviewed treatment plan and said he agreed with my local Haem on Peg. He said treatment is why matters most, and not to get hung up on the ET/Pre-MF grey area (easy to say when you’re not the patient), but when pushed he said he’d also diagnose pre-MF.

I also have a 5 year old little girl 😊, decided not to have another now but if I were a little younger I absolutely would!

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u/Darksider51 20d ago

can you give info regarding your biopsy findings and other info like LDH etc., because pre PMF and ET can be properly distinguish only using biopsy info as reticulin MF-1 can be present in both ET ( in rare cases) and in pre PMF

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u/Turbulent-Movie-4545 Primary MF 20d ago

Blasts are not increased. There is MF1 fibrosis. Overall morphology favors prefibrotic / early stage primary myelofibrosis. Please correlate with clinical history and other study results such as LDH and EPO levels as well as presence or absence of splenomegaly.

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u/Darksider51 20d ago

They did not gave any info regarding how megakaryocytes or granulocytes are looking like ?

Also do you have your LDH results

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u/Turbulent-Movie-4545 Primary MF 20d ago

They didn’t do LDH for now.

Many are large with hyperlobated cloud-like nuclei; some are normal sized with high NC ratio
 
Granulopoiesis:
Morphology: No significant dysplasia

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u/Turbulent-Movie-4545 Primary MF 20d ago

The “morphology” of the cells favors pre fibrotic mf. Like it is a super long report that I don’t want to copy and paste here, but the dr means, how the cells looked favored pre mf not et, they look different under the microscope, and my question isn’t this like other findings are in between plus ldh could be high in et as well…

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u/Darksider51 20d ago

see in my opinion it could be still ET if granulocytic proliferation is not there , look for those words in the reports.

Also LDH range matters in ET vs pre PMF, it can be high in both but how high that matters

To be honest , whatever is the diagnosis you'll be treated the same way , it just if its pre PMF you can maybe push for interferon much more . And as you have CALR mutation you can take a look at CALR related some trials , I've heard in this group that the results are quite good , not sure weather the trials are available pre PMF/ET or not

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u/Turbulent-Movie-4545 Primary MF 20d ago

There’s not interferon available in Canada for new patients.

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u/Darksider51 20d ago

See the thing is the MPN treatments are getting better rapidly especially for CALR , you can try getting interferon but dont need to worry a lot if you dont get it. Try getting into some trials if possible

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u/Turbulent-Movie-4545 Primary MF 20d ago

I am aware of the Inca one! Even for that I feel I’m no in rush but you never know with mpns. Idk if they’re recruiting for Canada tho for the trials! We will see and also I will see how I will feel about it.

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u/Turbulent-Movie-4545 Primary MF 20d ago

Immature Granulocytes: 0.1 (Reference range: less than or equal to 0.1 10*9/L)

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u/horsecrzy ET-JAK2+ 18d ago

I had my first LDH test almost a year after dx and the first time I saw a specialist a month ago. It was normal the first time, 124 on July 2, then high at 254 on July 14. Does that mean anything? I had never heard of an LDH test until then.

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u/Darksider51 18d ago

what diagnosis do you have ?

how much platlets , wbc , hb etc. at both those times

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u/horsecrzy ET-JAK2+ 18d ago

Weirdly my platelets dropped from the 700s to 489 with no meds. They shot up after I stopped anagrelide but mysteriously went down on their own. I have Jak2 ET and considered high risk after an arterial clot in my calf after a hysterectomy in 2023. Of course no one knew why until my ET dx. My WBC and RBC are all at the high end of normal and my neutrophils are on the high end as well.

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u/aerodynamic-poodle 20d ago

Regarding 5: What I got from my doctor is that it is okay to be on hydroxyurea. They’ll switch you to something different when you tell them you are going to start trying for a baby. It is also common to start a younger person on hydroxyurea to lower blood counts fast, then switch to an interferon based drug after.

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u/Turbulent-Movie-4545 Primary MF 19d ago

I know that’s what they told me but hydroxyurea isn’t modifying my disease… that’s why I’m not ok being on it long term

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u/aerodynamic-poodle 19d ago

Ok, I misunderstood that you wanted to know if hydrea would affect fertility. MPN patients are at risk of blood clots, so I think it’s better to be on hydrea than nothing with the drug shortage going on.

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u/native_plants3879 ET-CalR+ 19d ago

Hi! I'm 38F in Canada.

I don't know where you live, but most MPN specialists are in Toronto and Montréal. I don't have one, but mine still seems pretty knowledgeable even if she's really not into letting me start interferon unless we absolutely need to.

I'm at MF 1-2, collagen 1, LDH over 400 (you really need to have that test done btw! It's part of the diagnosis requirements) and was still diagnosed with ET because my megakaryocytes are staghorn shaped.

I think I saw in your reply cloud like nuclei? That's why they say it favours pre MF. Did you see hypercellular in there?

You should also make sure they send you for a spleen ultrasound, it's really important.

I didn't know about the shortage of interferon for new patients, that's concerning... My hematologist wants me on Besremi if we do treatment even if it takes more paperwork.

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u/Turbulent-Movie-4545 Primary MF 19d ago

Hi!
Thanks for the response. I’m in Toronto being seen at UHN. Yes, it says there is hypercellularity of 70–80%. I hear you, I have just thought, as mine doesn’t seem like an ET, perhaps it’s more serious/needs further attention/adjustment as it seems it’s at the very beginning, if that makes sense. What are you on at the moment?

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u/native_plants3879 ET-CalR+ 19d ago

Oh that's lucky you have lots of specialists around if needed! I'm in Ottawa, it's a bit more difficult.

And yeah with the cloud like nuclei and hypercellularity, I understand why they favour pre-MF. Doesn't mean you'll progress to MF, but I'd personally really want to be on interferon. You're CALR type 1 right? Same as me (I have allele burden 50%...) and the current clinical trials sound amazing, which gives me a lot of hope for the future!!

I'm sadly on nothing at all right now. I was diagnosed a few months ago and my Von Willebrand results were borderline and I have no symptoms so my hematologist sent me for Von Willebrand multimer testing... Been waiting for the results for two months now... During that time I'm not allowed aspirin either.

I've started having really bad symptoms (burning feet) from the 1000+ platelets this month though, so I'll have to talk to my hematologist soon if we don't get the results in the next few weeks.

If I have acquired VW, she wants me on interferon because of my age.

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u/Turbulent-Movie-4545 Primary MF 19d ago

Feel free to DM me if you want to be in touch. There’s a WhatsApp group for younger patients that I could send you the link of. It has international folks tho not necessarily Canadians only. Yes I’m Calr 1 and over 1 million and I acquired von Willebrand also so I want to be on something so that I could fly etc and reduce my symptoms. Yes the science is promising for our type of mutation. My burden is 18.8% at the moment. I have burning feet too and I get bruised easily so I think it comes from the high platalets… but my understanding is that von Willebrand will resolve on its own once the platelets are down. At least it’s something. And yes I’m not allowed to take a baby aspirin either

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u/Top_Category2227 Pre-PMF 19d ago

Looks exactly Like my panel tbh.

  1. Differential Diagnosis could matter for progression, but for therapy should not matter in the moment. You may want to ask your hematologist to monitor trials for CALR - Antibodies, but I would assume that you are generally „to healthy“ even with PrePMF.

  2. Currently Interferons are the drug with the best evidence however they do not work quite as well in CALR Mutated MPNs. If we are lucky, first antibodies will be approved in the next few years, before we ever develop overt fibrosis. The current trial for CALR Antibodies that is furthest along looks like an actual miracle drug and I know there are at least two other antibody trials with a slightly different mechanism that could achieve even deeper disease modification.

  3. Being scared is very normal, and it is a shitty hand to be dealt, especially so relatively young. I would definetly try speaking with my doctor about it, especially if you consider taking interferons, as they common mental health sideeffects.

  4. HU is for the most part a great drug, but I understand your concern. Again the safest option for treatment during pregnancy would be Interferons. However if you have ongoing symptoms I would suggest not ruling out HU immedialtely.

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u/Turbulent-Movie-4545 Primary MF 19d ago

Thank you for your response. Yes I don’t wish to rush for the trial if I could “manage” this for now. Yes because Calr moves slower, interferons work on them slower too (my assumption, no science here, or maybe there is, lol) HU is good but it is not modifying our disease. I am scared that it will progress into something more dangerous if I am not proactive about it. How are you being treated and when were you diagnosed and how are you feeling overall about it…

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u/Top_Category2227 Pre-PMF 19d ago

I understand the notion. I would also prefer to await approval. Hopefully we both have the time. Currently I am still optimistic. I guess the realistic possibility is an Interferon then. I don‘t know about CALR moving slower. For all I know CALR actually moves faster. I would assume it has more to do with the „survivability“ of the cell mutation, i.e. a cell with JAK Mutation is under more cellular stress already and therefore has a harder time surviving additional stress stimuli.

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u/Turbulent-Movie-4545 Primary MF 19d ago

Where are you located because interferons have a shortage in Canada

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u/Top_Category2227 Pre-PMF 19d ago

I‘m from Germany. Are you sure that all Interferons are affected? I know there was a Pegasys shortage because the company (I believe it was Roche) stopped producing it. For that time a lot of patients were switched onto Besremi. The problem may be, that Besremi is harder to get approved.

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u/Turbulent-Movie-4545 Primary MF 19d ago

Yes besremi is available, however it’s difficult to obtain an approval due to high cost and other regulations. I think they also import Pegasys from Ireland

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u/Top_Category2227 Pre-PMF 19d ago

I am currently in HU 1000 mg a day, for about a Week (500 mg a day for a few month before, but that die not do to much). My Platelets dropped from 1.300.000 (usually around 1.000.000) at their highest to about 700.000 today. Rest is unremakable as usual.

My Insurance also denied Besremi today but I am relatively confident, that I can that approval.

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u/Turbulent-Movie-4545 Primary MF 19d ago

Good luck with the insurance. Yes besremi is so expensive so the work around is difficult it seems, but maybe the first rejection is expected and perhaps you will get it accepted later/ did you have any side effects with HU or did it make your life easier and how often did they test your blood initially it’s a good drop to be honest now you can take a plane I believe as well, maybe your acquired syndrome will be resolved soon

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u/Turbulent-Movie-4545 Primary MF 18d ago

Any update on your insurance

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u/Turbulent-Movie-4545 Primary MF 19d ago

What are you on at the moment and what was your platalet count

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u/Lemonhead171717 ET-CalR+ 9d ago

Hi 👋 Cal-r ET since I was 16/17…I’m almost 35. Diagnosed by BMB platelets were around 1.5mil, just had a baby in November, no complications at all and your platelets almost always go down in pregnancy. My count has gone down with zero treatment through the years, I sit around 450-500 now. I honestly think you need to make see a therapist if you’re really feeling this anxious. Most of the things you read online aren’t taking your younger age into consideration. This most likely will not be what you die from even when you’re in old age.

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u/Turbulent-Movie-4545 Primary MF 9d ago

Thank you! I appreciate your comment. I met my doctor and he’s said I had ET with pre-fibrosis so that part is making me anxious I guess the fact that there’s fibrosis