Good news re allele burden

[Marossi]

Today my haematologist told me my allele burden has decreased from 75% to 33% since this time last year. I have been on Pegasys since December 2017. The first year did not see any reduction in allele burden; in fact there was a slight (probably statistically insignificant) increase. So you can imagine my delight when he gave me the good news today. He said he was not surprised and that for him this was just the confirmation that Pegasys is a slow-acting drug and that it’s important to be patient.

[Aneliv9]

Is this decrease means that disease progression is slowing down?

[Marossi in reply to Aneliv9]

Well, I think it means the disease is less aggressive now so hopefully yes.

[Aneliv9 in reply to Marossi]

This is what your doctor told you? Or you make a hypothesis?

[Manouche]

Fantastic news! Did you write earlier that you blood count took about a year to get under control ? This would perhaps explain why it took over 2 years to decrease the allele burden. Studies have shown that it could keep decreasing over the next few years of treatment with pegylated interferon.

[Marossi]

Thanks. Yes, that’s what I’m hoping. My haematologist has always told me to be patient, that it’s a slow-acting drug. Hopefully this can encourage some other users of Pegasys.

[mhos61]

That’s great news Marossi. It’s a substantial decrease in your allele burden. I can see why you’re elated. You couldn’t wish for a better Xmas present.

Best Wishes

Mary 🤗

[Photoshopuser]

Very happy for you

[tracey13]

Fantastic news!

[Mazcd Partner MPNVoice]

Brilliant news, so pleased for you. Maz

[Susana7]

Wonderful news! Very happy for you! That is a huge drop. I have been on Pegasys for over 4 years. The allele burden is not routinely measured in the U.K. on our National Health Service, so I can only hope the same is happening to mine ☺️

[Marossi in reply to Susana7]

🤞

[JackLina in reply to Susana7]

Hi Susana. I'm replying to you because you mention that the allele burden is not discussed in the UK and that is something I have found increasingly annoying. Not least because the % of the allele burden can dictate the likelihood of further mutations.

To date I have still not been able to find this from my haematologist and I know it's there somewhere because I was DNA tested in January 2018.

I too am using Pegasys and really hope it is having a similar effect to Marossi.

All the very best for yours!

[azaelea in reply to JackLina]

Hi, I'm in UK Too and have found it really annoying that I have never been told the percentage of my Allelle burden. On every visit to Haematology this year,I have asked each person what mine is and am still without an answer. I wondered if it had more significance to PV sufferers than to ET. I have ET Jak2+ and on my last consultation with the Haematologist at the beginning of this month when I asked yet again, she said they don't attach much importance to the Allelle Burden percentage! Don't understand this at all when it can tell you how strongly the blood disease is affecting your body and also detect any further mutations. The Dr. did not attempt to look it up on the computer and just dismissed it. I wondered if it is only evident from the results of BMB . Mine was done in August 2018.

[mhos61 in reply to azaelea]

Ditto!

The letter from the Consultant to my GP after my initial diagnosis (I was copied in) says that the Jak 2 mutation has been detected at more than 1%. Why they couldn’t put the actual percentage is anyone’s guess😡

I have asked the CNS a couple of times, but they can’t seem to access the information for me. I find it annoying too.

[Marossi in reply to azaelea]

No I’ve never had a Bone marrow biopsy. The test was done from a blood sample.

[azaelea in reply to Marossi]

Oh, thanks for your reply. I didn't know it could be obtained from blood sample.

[JackLina in reply to azaelea]

Hi azaelea. I have managed to get all my blood results and the assessment from Leeds that stated I had a JAK2 mutation. That is where I would have expected to find a % of mutation but it isn't there.

When I had all the original tests in hospital in January 2018, I had a lumbar puncture and therefore, presumed it was from there that these findings arose but apparently not.

Regarding the importance, it is the same for PV and ET but it seems (if you read elsewhere on this site) that the UK doesn't bother with it but the US routinely checks it each time they do tests. I didn't realise until recently that all this can be found in routine blood testing.

See this article regarding testing for mutations and their significance.: jcp.bmj.com/content/72/2/172

[Marossi in reply to JackLina]

Hi Jacklina, just wanted to say that the mutant allele burden is not part of routine blood testing. My haematologist has to send the blood sample to a specialized lab in another part of the country to have it done and so far he has only done that twice (once after a year of treatment with Pegasys and again a year later.) Normally when I have my blood tested I just go the hospital half an hour before the appointment with my haematologist. The nurses take my blood and 20 Minutes later send the results to my doctor so they are ready for us when I walk in. It takes 10 days to two weeks to get results back from the specialized lab.

[JackLina in reply to azaelea]

Hi again Azaelea. Sorry, I put an article on there that doesn't mention the allele burden but all about JAK2 mutations.

However, if you look back at 'hunter5582's post, you will learn a lot about the significance of the burden on ETs such as you and I. All the best Penelope

[azaelea in reply to JackLina]

Thanks so much Penelope, I will have a look at the article nevertheless and I do remember Hunter's post a while ago which I will look at again. Many thanks. Fran

[hunter5582 in reply to azaelea]

JAK2 mutant allele burden is relevant to all MPNs. The lower the percentage, the lower symptom burden tends to be. Tendency is ET has the lowest, MF the highest, PV in the middle. Less than 50% is indicative of lower risk symptom burden. Not all docs pay any attention to this. Not all agree with its relevance. This is emerging research on MPNs and many hematologists do not bother to keep up with current research on MPNs because they see so few patients with them.

For all those pushing for more information form their providers - assertive patients get higher quality care. Passive patients do not.

[azaelea in reply to hunter5582]

Thanks for your reply,Hunter. It was because of one of your posts a while ago that I persistently asked for my Allelle burden percentage at each Haemo visit but it seems that my Haematology department must be one of those who do not attach any importance to it. Although it's one of the largest hospitals in Britain, I'm not too impressed with Haematology! I'm up in N.E. England and not near any of the Specialists listed unfortunately. Best wishes,Fran

[hunter5582 in reply to azaelea]

It is worth travelling to at least occasionally consult with a true MPN specialist. Many hematologists do not have the KSAs to effectively treat these rare disorders. Certainly not with the nuance and willingness to stay state-of-the-art in the treatment we all deserve to receive. I have about a 2 hour drive to see the M<PN specialist I consult with. He advises me and my on-going hematologist regarding PV treatment.

I expect you have looked at this list before, but here it is again mpnforum.com/list-hem/ . You are asking a perfectly reasonable question in wanting to know what your mutant allele burden is. If your current providers are unwilling to provide the care in the way you wish to receive it, then perhaps it is time to fire those docs and seek care elsewhere. At a minimum, please consider travelling to get a second opinion or ongoing consultation. If the current docs have a problem with that, then in my view they are prioritizing their egos over your care. Ultimately, you are in charge of your care and the direction it needs to go. It is your body - it is your choice. Any provider who has a problem with that does not deserve to provide your care.

All the best to you.

[JackLina in reply to hunter5582]

I have been told mine now, since changing haematologists. It was on the original assessment apparently from Leeds. Although I think the % I was taken is from my last test in December. Of course, best to know what it was when first diagnosed and what it is now that I've been on Pegasys for 21 months. I'll investigate further on my next appointment, now I have a specialist who converses! x

[hunter5582 in reply to JackLina]

Having a doc who actually talks to you is really important. Glad to hear you have one now.

[Hidden in reply to azaelea]

Do you not have a right to that information? Even if it is not important to them - they did the test, it is your info - and why the heck did they do the test anyway if it gave them such little information. Not making sense in my head

[Susana7 in reply to JackLina]

Hi Penelope, yes I agree, it is very annoying. But given the current crisis on the NHS I can understand why they don’t prioritise offering this test routinely given the lack of immediate prognostic relevance. My MPN specialist did say she would consider getting it measured once she thinks I am in remission, say injecting a small dose only once a month, with stable counts. I currently inject 45mcg every 3 weeks, so am getting there! All the best to you, and here’s hoping our allele burdens are silently spiralling down, in the background! Susana x

[JackLina in reply to Susana7]

My haematologist doesn't want me to know anything, it seems. In fact, he has ignored my requests to know my original allele burden. He doesn't know what it is and appeared to have no intention of finding out.

What I do not understand is why his interest in learning more about this condition appears to be none existent. Surely, if this was considered in the initial testing, it could be assessed as reducing or not based on the drug being administered.

If there is a gradual decrease in the allele burden, over a period of time on a specific drug, then surely that would be of interest to any haematologist, as it would support their prescription.

Just a thought! All the best Penelope

[Bohus]

Does anyone have any tips regarding reading what allele burden is. Sure I know how to use Google but I would like to read about it from an MPN point of view.

[Marossi in reply to Bohus]

This might help:

patientpower.info/myeloprol...

[Searcher56]

Can you explain what this "allele burden" is and what test is used to determine the size of it? I am ETJAK2+ and I had a DNA test done for the purposes of taking part in a drug trial. I did not qualify for the trial because I did not have enough of the gene mutation in my blood. Is this allele burden the same as the gene mutation?

[Marossi in reply to Searcher56]

I think it is, roughly speaking. I found the site patientpower.info to be really useful in helping me understand the significance of the allele burden in MPNs. There are several interesting articles which explain it much better than I ever could.

[Searcher56 in reply to Marossi]

Thanks for the tip.

[Stevesmum42]

You best Christmas gift. Great news

Regards Sandy.

[Bears23]

Wow, thats really good new! Very happy for you and thanks for sharing!

[azaelea]

Great news, Marossi. Happy for you! Regards Fran

[jointpain]

Hi, my wife saw her hematologist yesterday, while with him I asked if there was a record of her allele burden percentage. He said it is not measured in Wales, nor in Liverpool or Manchester. The only place he says it can be measured is St Thomas's in London. That was because they have a research facility there. I asked as I thought maybe peg interferon may actually cure the MF my wife has, by destroying all the jak2 positive cells. Seems it was an ask too much.

[jointpain]

I knew that

[Cja1956]

I just re-read my results from my most recent BMB and it said “mutant allele burden % 63.5 and then under that it said 6.3. It also said I had a high allele burden. I was diagnosed with post ET MF. I never paid attention to my allele burden until now and my hematologist has never talked about it so I don’t know much about it. But it sounds like it’s a good thing yours decreased. May you continue to have good news.

[welshhuw]

That's great news, hope it continues to decrease for you. I have been on Pegasys since March 2019 and my platelets have decreased from 1.2M to 300K, over about 6 months. I have ET CALR type 2 but it seems allele burden testing isn't available as yet for this mutation in the UK which is a pity. Would be interesting to see if it is reducing. Just wondered what dose of Pegasys you are on ? I was on 65mcg weekly but due to some side effects it has recently been reduced to 65mcg every 2 weeks. Won't know if this dose is still effectively controlling my platelet count until my next test in Feb. All the best, Huw

[Marossi in reply to welshhuw]

I’m currently on 90 mcg every 3 weeks. I was on 135mcg every week for several months and even then needed venesections on top of that to keep the haematocrit below 45. Altogether it took about a year of treatment with Pegasys to get blood counts fully under control. Hope the dose you’re on manages to control your platelets.