Update 7.2

[hunter5582]

On the whole the news continues to be good, with a bit of a caveat or two As my iron levels increase, so does the erythropoiesis. Not a surprise, just basic PV iron physiology. While I have been hovering above and below goal of 45%, the last two reads were 46.0 and 47.9. HGB is also steadily increasing, now reading 15.5. Time to do something different. I will post the numbers below.

I met with my MPN Specialist, Dr. Jain, on December 22 to review my status. The other caveat, continued elevation of Liver Function Tests (LFTs) was something we discussed. Current ALT=157, AST=94.0, ALP=211. All three the highest reads to date. The current elevations are not a concern as they do not meet the threshold of 5X Upper Limit of Normal (ULN). This is just part of what can happen when using the IFNs to treat PV. We will continue to monitor at 8-week intervals and keep an eye on the LFTs to ensure they stay below 5X ULN.

Dr. Jain does use HCT as the target to follow. We are in agreement that we do need to get the HCT < 45%. We discussed the two options of increasing Besremi or doing a venesection. Due to the LFT elevation, increasing the Besremi dose could be problematic. We decided to opt for a venesection at this point in time. Hopefully we can nudge the iron levels down just a bit to get the HCT a little below 45% - but not so low that I experience a return-to-symptom of iron deficiency. I am going to opt for a mini-phlebotomy (300ml) to see if that will work. Dr. Jain supports that option as worth trying. I can always repeat with another mini-phlebotomy if needed.

My hope is that the longer I am on Besremi, the more long-term benefit I will accrue. Hopefully,, I can eventually let iron levels return completely to normal while maintaining HCT < 45%. When rusfertide becomes available, I may opt for combination treatment if still needed.

Dr. Jain did agree that the reduction of JAK2 VAF from 38% to 9% is a good thing. She compared it to the reduction in VAF with other hematologic malignancies (eg., CML). We cannot yet prove how much of a good thing it is, but it cannot help but to be a good thing in the end.

I am planning for continued success in managing the MPN. Wishing you all the same moving forward.

[hunter5582]

CBC

CBC

[hunter5582]

CMP

CMP

[hunter5582]

Iron

Iron

[azaelea]

Hoping all goes well for you and with the help of your great medical team things can come back to as normal as possible. Hope you had a good Christmas and all best wishes for 2023. Kind regards, Fran

[Mostew]

Good to see your update. May the New Year bring you continued positive results and energy to deal with hiccups along the winding road

I hope you got things sorted at Church and enjoyed the service s

[JeanieRN]

Hi Hunter, thanks for the update! I will be following your progress and wish you the absolute best! Thank you for always willing to explain things and share your experiences. It helps more than you know! I too am on Besremi 100 mcgs some elevated LFTS and my iron level is 11. Happy Holidays to you! May the NY bring us health!

[Manouche]

 »Dr. Jain did agree that the reduction of JAK2 VAF from 38% to 9% is a good thing. She compared it to the reduction in VAF with other hematologic malignancies (eg., CML). We cannot yet prove how much of a good thing it is, but it cannot help but to be a good thing in the end »

It works with Ruxo, so I suppose it should work with Besremi as well !

Molecular response

[EPguy in reply to Manouche]

A study of MR vs MFS is novel I think. I recently posted on a Type 2, 2nd gen Jak-i that is in R&D. Their top claim is better MR. If so the plot you show here would show a good reason to use the new Jak-i when it comes out.

[FG251 in reply to Manouche]

What’s ‘DMR,’ please?

[Manouche in reply to FG251]

Deep Molecular Remission

Molecular Response

[FG251 in reply to Manouche]

Thanks. And do we know what % allele burden constitutes a DMR, as opposed to CMR?

[Manouche in reply to FG251]

As far as I know a DMR is defined as <1% of mutated jak2 hematopoietic cells

[EPguy in reply to FG251]

In another thread on CML, they use 0.01 or less, but they have a different reference since they can more easily get to these extra low values. Interesting the different reference points.

[EPguy in reply to Manouche]

In the table you have here is a new piece of info to me. Haplotype 46/1 is a negative prognostic for MR on Rux. Maybe similarly for IFN, but the data is only for Rux.

"The frequency of the JAK2 haplotypeGGCC_46/1 in the healthy population is about 24%, whereas it was found in 40–80% of JAK2 V617F positive MPN"

So 20-60% of MPN patients don't have 46/1 and maybe these see the best MR on Rux.

ncbi.nlm.nih.gov/pmc/articl...

Haplotype 46/1 happens before the Jak2 mutation (I think it's in the germ line from birth) and makes Jak2 mutation more likely.

[hunter5582 in reply to EPguy]

Correct about the JAK2 46/1 haplotype. It is a germline part of the genome. It is thought to predispose to acquiring the JAK2 mutation. My daughter and I are positive for both the JAK2 haplotype and JAK2v617f. We both were diagnosed with a MPN in our 30s. Genetics do matter.

[EPguy in reply to hunter5582]

Thanks for the details. My NGS did not mention this. Is it part of the allele search for mutation, or part of the Karyotyping (I think Karyo is the cytogenetics chromosome search)

In other threads we discussed alleles being mutated genes while cyto is looking for missing, extra, or misplaced genes that aren't necessarily mutated. So 46/1 should be one of these two defect types I think, and I assume would show up on a typical NGS. If not I'll ask Dr about it.

According to bmcmedgenet.biomedcentral.c...

these numbers should show up with 46/1:

"rs10974944 (C/G) and/or rs12343867 (T/C)"

[hunter5582 in reply to EPguy]

The JAK2 haplotype is a specific alteration in the genome that has to be looked for specifically. It would not e looked for on a typical NGS for MPNs. As it happens, the 23&me panel does assess for this mutation. While not "medical grade" testing, this panel can provide some interesting information.

I expect most docs would not bother with ordering the AJK2 haplotype test. if you are already JAK2 positive, it is kind of a moot point.

[EPguy in reply to hunter5582]

Interesting note on the consumer test. That was where I saw it from a worried forum member who received this result from such a test.

In this older report:

ncbi.nlm.nih.gov/pmc/articl...

"The 46/1 haplotype of chromosome 9p, present in about 45% of the general population,.."

I've seen lower numbers elsewhere but still 20-30+ %.

Maybe it's so common that the Hematology field does not find it useful to know. But it does seem relevant.

[EPguy in reply to hunter5582]

Haplo seems to be of particular interest for genealogy as in "23 & me" you referred to.

"..because your haplogroup only tells you about direct paternal-line or maternal-line ancestors"

customercare.23andme.com/hc...

This site has a whole page about haplotypes. But maybe it is worth knowing for hematology too.

[hunter5582 in reply to EPguy]

The 23&me genetic study is not considered a medical grade test. More for genealogy and general interest. It is being used in some genetic studies. I find it to be more of broad general interest abut your relative medical risk factors and maybe giving an indication of something that would be worth looking into in more detail with appropriate medical testing. For my daughter and myself, knowing we are positive for the JAK2 haplotype is a bit of redundant information since we are JAK2v617f positive and have a diagnosed MPN. We are participating in one of the the Familial MPN Studies. Hopefully, we will learn more over time about the underlying genetics of MPNs. I certainly believe that the individual's genetic profile bears on treatment efficacy. Another topic that needs further research.

[EPguy in reply to hunter5582]

It's possible the haplotype is worth knowing at least with Rux, from the above report it is prognostic for MR. But the way it is discovered, via consumer testing, would make researchers wary.

Based on your experience, having 46/1 has not prevented your great MR on IFN.

My impression is haplo is a broad set of long-ago inherited variations among all people useful for knowing ancestors. Jak2 allele sits within the area covered by the 46/1 haplotype.

[EPguy]

Nothing is 100% in our journey.

Your Red counts all are trending up. Another member recently had high HCT but low Hb. Hard to figure that one.

Agree on rusfertide, this should help gently balance the HCT issues with IFN. My Dr said he would not combine them, but once it's really available he might reconsider maybe. So far I'm ok on HCT but not by a lot (44.3).

Along with the LFTs, your Lymph is also still where you wouldn't want to increase the Bes. I'm at a dose limit from WBCs. Another indication we need the rusfertide option.

Your "ones that don't matter" as my Dr says, are out of range. (MCV, MCH, RDW) I wonder if there is any connection to other effects of the IFN.

Re CML, did your Dr point to more solid data supporting a VAF benefit for CML?

Your iron result is yellow but is in range. Is that right?

Overall still looking good, wishing you that continued good accrual.

[hunter5582 in reply to EPguy]

Managing a MPN is always a balancing act. On the whole, I continue to be very pleased with how the treatment with Besremi is going. I would be willing to risk an increased dose if the LYMPH was the only issue but together with the LFTs, I am thinking that 150mcg may be my max tolerable dose.

Will give the mini-phleb a try and go from there. We will see how i goes from here.

[william-Indo]

Happy to see your update Everything is good shape

Up and down slightly in some of your blood profile is normal.

Wishing you merry x'mas and a very happy new year.

Cheers

[gilded]

Hunter, thanks very much for generously sharing this with us on this forum and wishing you all the best.

[Manouche]

Hi Hunter,

« The other caveat, continued elevation of Liver Function Tests (LFTs) was something we discussed. Current ALT=157, AST=94.0, ALP=211. All three the highest reads to date »

Did you take a large amount of Vit C recently ?

 »Aim: To investigate if mega-doses of vitamin C would have deleterious effects on the liver. Methods: A mega-dose of vitamin C (1000 mg/kg/day) was administered by oral gavage to male Wistar rats for 60 days. Both biochemical and histopathological measures were undertaken. Results: The results showed that a mega-dose of vitamin C significantly elevated lipid peroxidation and transaminase activity level in addition to the significant suppression of antioxidant enzymes activities. These results were consistent with the presence of histological lesions. Conclusion: A mega-dose of vitamin C is not safe and can cause liver injury »

researchgate.net/publicatio...

[hunter5582 in reply to Manouche]

Negative to the high dose Vit C., but thanks for sharing the information. I am endeavoring to be kind to my liver.

[Alexbits]

Thank you for the details. I'm in 3rd year on Peg-INF, and I had the same issues with liver enzymes when injected every seven days. After moving to 10-day intervals, the problem was fixed, except for the ferritin, which was still pretty high,> 300. Now I'm on a 14-day/45-55mcg schedule. The HCT is a very stubborn thing. It took me a year or more on Peg to get it under control.

cbc graphs

[Poppy6060]

Hi hunter thanks for posting you are always helpful hope things improve for you I am on Pegasys every two weeks and only a few weeks ago was told my liver test was slightly high so have a blood test next week happy new year to you best wishes Poppy

[Mishie14]

I have so much to learn about this ET journey....Thank you very much for being open to sharing personal information so that others can learn and be wiser along the way. I also appreciate your always positive attitude and lifestyle that clearly demonstrate MPN is manageable. Some days are hard and others not so hard but ET is always hovering around me in some way. You have helped me understand so much more about this than my doctors have let on. You are a role model patient and teacher. You are appreciated. May 2023 be a breakthrough year for MPN drugs and treatments. Stay safe!

[Bluetop]

All about balance I guess and I understand it is likely to take a while for the interferon to settle. Good luck, I hope the mini venesection helps you on your way.

[Looolooo]

I was due my first mini venesection today after being on peg 90mcg a week for 9 months (pv previously controlled by energy sapping venesections + aspirin only). Peg had been progressively slowing down rise in hematocrit. But I just got some great news. For the first time since being on Peg my hematocrit has gone down from 0.44 to 0.43, all on its own, so no venesection needed. You might just be a few months away from a similar result, so don't lose heart.

[hunter5582 in reply to Looolooo]

I have popped up above and below 45% the last several times. Been letting it ride but we decided it was time to get back below 45%. I would rather have increased the Besremi dose but with the elevation in LFTs it is not the best choice. Confirmed with my regular hematologist today that we will try a mini-phlebotomy or two and see how it goes. That doc thinks a full 500 ml or two would not drop me so low on iron that I would have the same problems as before. However, i want to give the mini-pklebs a try. Hopefully it will nudge down the levels just enough to give the Besremi more time to do its thing. Definitely going to pna for success on way or another.

[Nikon7]

I’m in the same teeter-totter balance as you with LFS slightly elevated but HCT sometimes above 45 and needing a phlebotomy. I’m trusting my 150 mcg of Besremi is steering me toward calmer waters and the Rusferitide Phase 3 trial has me hopeful. Onward we trust in the workings of our bodies and science! 💪😉

[CLONDARA]

Hope all goes well for you in 2023. I have appreciated all your posts since I joined this site. As you share, I and I imagine many more learn so much, so thank you. Valerie

[Kelly2]

What is Rusfertide for Hunter? That post was two years ago. How are things now?

[hunter5582 in reply to Kelly2]

Rusfertide is a hepcidin mimetic. It is an alternative to venesections for controlling erythrocytosis. It works by keeping it in storage so that it is not available to make RBCs. It may prove easier to tolerate than the long-term iron deficiency that venesections induce. It will hopefully come to market soon, hopefully later in 2025.

[Kelly2]

I am having a biopsy on Tuesday. My new doctor thinks that I have progressed to MF as my reds are low! So what happens next? I give up or there are medicines for this? I guess I'll know soon. I will need your help and support Hunter. I am so afraid I cry all the time!

[hunter5582 in reply to Kelly2]

Sorry to hear about the possible progression to MF. That is very scary. The good news is that treatment options for MF have improved considerably. Momelotinib was recently approved for use for MF w/ anemia. This is another JAK inhibitor which is more effective than ruxolitinib for people whose MF includes a lower RBC count.

There are also other treatments in clinical trials that are hopeful for further expanding options. There is real reason to have hope for continued improvement in treatment outcomes.

It is scary to face the possible progressions in a diseases like MPNs. We all need to find our own ways to cope, One of my main coping mechanisms is to educate myself so I can make decisions based on facts rather than fear. MPN Voice has good information on the website. MPN Education Foundation has a history of providing excellent training. They just put out their 2025 updates, which I have not had time to review yet. It is on my agenda. If you are interested and feel it will help, suggest you gather more information. The link is below. Note that the Managing MF in 2025 is mislabeled in the index. It is the presentation by Naveen Pemmaraju. There is also a presentation by John Mascarenhas on New Drugs for MF. If you want to know more about MPN Molecular Biology, the presentations by Jyoti Nangalia are always informative. mpninfo.org/conferences/202...

Education is only one part of coping. Here is my list of coping strategies.

1. Support from my family, friends, and faith community.

2. The MPN forums (my friends and MPN Family)

3. Maintain your sense of humor and find ways to have fun no matter what.

4. Surround yourself with things that are positive and lift you up.

5. Mindfulness practices - I practice Qigong.

6. Say the Serenity Prayer every day and take it to heart!

7. Educate yourself about your condition(s). Knowledge is power.

8. Create a high-quality treatment team who you trust.

9. Advocate for yourself. Assertive patients receive higher quality care. Passive patients do not. Remember that you are in charge of your care. It is your goals, priorities and preferences that must drive your treatment. Empower yourself to deal with the MPN.

I have led a long rich life despite 30+ years managing a MPN. I plan to continue to do so despite what happens with the MPN. Sure - there have been some challenges with the MPN and the other related and unrelated medical issues I face. Sometimes you do, as the military folks say, have to "Embrace the Suck" or just "Suck It Up Buttercup." However - it is not all "Suck." There is plenty of good in life to enjoy and embrace. As the prayer says, I seek the serenity to accept what I cannot change, courage to change what I can, and wisdom to know the difference.

More than anything else at this point, know that you can manage this. There are ever-more treatment options and very real hope for MPN treatment improving in the foreseeable future. Have confidence that you will be one of many who do manage the MPN successfully. Know also that you do not have to do this alone. You will find support if you seek it, most certainly here on this forum.

You will be in thoughts and prayers. Please do let us know the results of your BMB and what your plan will be moving forward.

[Kelly2]

Thank you Hunter. I am fortunate to have found this community and you! It is just that I was optimistic counting on changing to Besremi and did not expect that. The only good thing is that I finally (too late?) found at last a new doctor and left the indifferent Professor I seldom saw! I have suffered a whole year first with my kidney operation, then my heart valve transplant and the cherry on top, this. In one year my life changed cmpletely. I will keep you posted. Thank you!🌹

[hunter5582 in reply to Kelly2]

Challenging times indeed. I remember well the time time period between 2018-2020 where I had four surgeries, including a cardiac catheterization and removal of a brain tumor. It was the same time frame where I found out I had progressed from ET to PV. Thankfully, I also shifted my treatment providers to include a MPN Specialist and a NF Specialist. Having two rare conditions to manage provides ample opportunities for health learning experiences. This is what caused be to be more focussed on how I was managing my physical and mental wellbeing.

Please do let us know what you learn from the BMB. Wishing you success in managing the situation whatever it may be.

[Kelly2 in reply to hunter5582]

I will. Thank you! I am so scared! He was so sure about it and said I was in denial!!!!! I will tell the doctor about the momelotinib! Here in this country I am from, doctors do not encourage patients to read and be informed about their condition!!! He also told me so and I said no I want to learn about new treatments and medicines. He said all the medicines existing we also do have them here! I hope he will prove to be good, another doctor recommended him to me as being a star in the good sense of course. The first day he sent me for blood exams. This hospital specialises in blood diseases and does transplants too which he said that due to my heart condition I can't have!! I saw a majority of women waiting to see doctors. Tuesday is the big day of truth. I will let you know as soon I do. I am counting on you for your advice on medicines as you know so much! Be well!

[hunter5582 in reply to Kelly2]

Sadly, there are still healthcare systems that do not respect the patients right and responsibility to be educated about their own health conditions. This is an outdated authoritarian approach that has no place in modern medicine. I would encourage you continue to educate yourself. Educated and assertive patients receive higher quality care. passive patients do not.

The best advice I can give on treatment options is to be clear about your treatment goals and risk tolerance. This will drive your treatment decisions. We are at a point in MPN treatment where we have moved beyond merely preventing thrombosis and hemorrhage. Effectively managing MPN symptoms, preventing progression, and overall survival are also important treatment goals. It is our right and responsibility to be the one who sets our treatment goals. We can then work through shared decision making with our treatment team to achieve the goals we set.

Wishing you success moving forward.