I’m Canadian and after reading posting on this site I’ve noticed the percentage of Alle Burden is often referred to, so I asked my haematologist what mine was when my results came back ET Jak2. He said in Canada they don’t think it’s relevant so don’t give out the percentages. I didn’t believe this answer. I’ve read that knowing the percentage gives one a good measure of their future prognosis . I was wondering if any other Canadians were given the reasoning that it’s not relevant to their progress or outcome. Thank you for bearing with me on this puzzlement my Doctor has presented me with. I will see him in about six months again.
thank you in advance.
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Suenami
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Hi, I'm in Wales, and also been told Allele burden not measured. I am doing a clinical trial for Ruxolitnib for PB and was surprised that this test wasn't done at the start of the trial. I would be very interested to know it , my haemotologist suspects it would be high.
we have same thing in Scotland, I had to get it done privately in England.
The allele burden doesn’t as you put it “give a good indication of prognosis”, there is no evidence of that yet as far as I am aware, we think low AB might be good in PV and ET but it’s still a grey area.
I’ve heard MPN specialists at various patient forums say they don’t currently know what to make of the AB/VAF data so don’t routinely measure it. They usually add that could change in the future when there’s a clearer understanding of what it means in practice.
I last heard it said in a MPN Advocacy & Education International ET video with Dr Gaby Hobbs. A link was posted here by Hunter a couple of weeks ago and it was a very informative watch.
I'm in England and have had similar responses from my haematologist. I think this is a generalist Vs specialist issue. I can be insistent and have now got them to agree to remeasure after 6 months. I may take the private route if that is not honoured v
The evidence that it's relevant is increasingly clear, but also mostly recent. Practice is conservative so it's still hidden or ignored by some Drs and organizations.
In the trial discussed here the benefit in reducing it was explicitly measured and demonstrated. I believe this is the only prospective trial to measure this benefit directly. But it is for PV and Rux was the treatment. There is less data on ET, both VAF reduction benefit and use with Rux.
There are various other less direct studies showing higher risk with higher VAF, discussed in many prior posts, usually in context of PV and IFN. Most address the level at Dx or some other unspecific time. Hence they are not clear whether reducing it is beneficial, but the strong implication is there.
The VAF% test (quantification) is not that costly so denying it doesn't make sense.
There is an emerging consensus that VAF is a valid marker of disease status; however, this is not in common clinical practice yet. I do believe that full genetic testing, including VAF and non-driver mutations will become standard of care in the near future. My MPN cre team does see value in monitoring VAF and we check on a yearly basis. There has been no problem with authorization through Medicare A/B and secondary insurance.
The movement towards tracking VAF will not happen without advocacy. That advocacy rests with us.
I am checked re bloods Exeter Hospital under Haemotology Dr Veale. But got all my advice & treatment experimenting by consulting with Professor Claire Harrison at Guys Hospital. Expert on MPN treatment . I got phone consultations . I also go to Guys when they hold their annual MPN conference. Professor Harrison helped so much as I was not coping on Hydroxy which Exeter put me on ,so changed to Peg Interferon. But she was responsible for managing my doseage as I was sensitive to any high doseage. . My local Drs were absolutely useless I really faught to get a diagnosis . Julia . 👌
The problem with Exeter & lots of other NHS hospitals is they automatically prescribe hydroxy as in my case. No suggestion of any other drug available. My body rejected it & hence I explored on this site other options. The Drs I saw were reluctant to prescribe Interferon probably I discovered , due to cost , hence I asked for second opinion from MPN Claire Harrison who prescribed my Interferon & doseage. You do not necessarily see Dr Veale as I saw 5 different Drs in Haemotology . Some were not very knowledgeable on this complaint or doseage of the drug.
I am now on shared treatment with Guys hospital & Exeter. I learnt on my journey with this complaint to find a drug my body coped with & quality of life. Not fast reduction of platelets. Interferon is working well with no side effects. Julia 👌
I asked Haemotology to refer me but they did not . I then saw my own Dr & asked for a letter to be sent to Professor Claire Harrison at Guys as I wanted an expert MPN to consider my treatment. Dr told me I had to do it through Haemotology but agreed to send a letter. I heard nothing so found an email address & wrote myself to Guys hospital outlining my concerns & reaction to current drug I had stopped due to side effects. I received a phone consultation and was the prescribed my Interferon . I again contacted Guys as local Haemotology told me to start on 90 injection weekly. I refused as read it should start low & platelets were only 590. Guys advised 45 weekly but later reduced to monthly a my body reacted to weekly feeling spaced out . !!
I am fine on 45 monthly no side effects. That is why it is important to consult a good MPN if you are not happy.
I still get treated at my local hospital re bloods but if any problems I have at least a 2 nd opinion expert to speak to .
Hope this helps . I was only put on anything as over 60 . 👍 Julia .
I have had phlebotomies during 25 years, Hydrea for a number of years after that, had to reduce the Hydrea to one per day with phlebotomies (less frequently). Patients with ET get anagrelide as second treatment option. Jakavi is also available since a 2 or 3 years.
Hi, this is a very interesting question. My hematologist put my Alelle burden on my confirmation letter (61%) at diagnosis. When I asked him about the need to try and reduce it he did agree that it was high and we should consider this in treatment plan, he also said he wouldn’t usually tell patients their % so I can only assume that it wasn’t meant to be in the letter.
I’m in Jersey, Channel Islands and he is a private hematologist.
Waiting for my BMB results to come back before a treatment plan is put in place, I’ve been told I won’t get the results for another 4 weeks and I had the test 4 weeks ago. Has anyone else waited this long for their results?
I am not sure I can answer that but I suppose 90-100 is high, however I know a few PV veterans 20 and 30+ years with AB in the 90's and I am not sure what difference it makes, both on Peg and one converted to MF after about 30 years ago. For many years they thought fibrosis in the marrow was a big deal and now recently they have found out its no such a big deal so who knows. I would speculate lower is better but if I remember correctly when some MF patients convert to leukemia they have very low MF. Dr Spivak told me year ago those with AB under 50% have a easier ride and , 61 is not so far from 50 and if you retested it might be different anyway, alleg its more accurate done from the marrow than blood. Its all a bit of a grey area currently so I wouldnt lose too much sleep over it, if it does bother you both Peg and Rux seems to lower it for some at least , not so for my veteran friends at time of writing.
ainslie I appreciate your response and am always blown away with the knowledge so many of you have on this site. Thanks for sharing your insight. At the moment I am not concerned with my AB as it started out at diagnoses at 11% via blood test and a couple years later was about 17% via BMB.
Some nice hard data on familiar risks in this video. The risks seem to be in order, but he was not explicit there. If so high WBC is really important while VAF is surprisingly low on the list. He dismissed the HCT result to confounding factors.
The connection of thrombo to progression might be a new finding.
1-High WBC, 2-Duration of PV, 3-Hx of thrombo, 4- VAF, 5-HCT <+45.
Still missing is prospective data on the benefit of reducing VAF which could confound all the above. This benefit is accepted by most of us but so far I know only the single Rux study that has looked for this explicit correlation.
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One area he seemed not up to date is his comment (approx quote):
"as we witness more drug development... we can find which agents can delay or reverse progression..."
For us here it's clear enough that we don't need more drug development to get this answer. One or both of IFN and Rux can do it well for many or most PV pts. But we all would welcome improvements to these.
A few months after my positive diagnosis of PV JAK2 in November 2022 I became aware of the Allele burden indicator as a potentially useful data point and discussed it with my hematologist. He seemed to be well aware of the studies being conducted and responded there was not enough data available to confirm its usefulness. Fast forward to this past January, and a few discussions about it with him during visits, I brought it up again with him and his response surprised me. He said our next visit, which will be in May, he will ask the lab to run the test, but will also check insurance, etc. to determine coverage. So I'm hopeful that I soon will have this measure and then the question will be what does it mean. I'm doing well on HU and low dose aspirin with all measures within range so we're in the "fine tuning" phase of HU dosage level, etc. Will keep everyone posted when I have something to report.
A fellow Canadian here :)! I'm in Ontario and my MPN specialist tested it when I first got diagnosed. OHIP (the public insurance covers it only once). Now, on the Besremi trial and I asked my doctor if we can test again, but OHIP doesn't cover it. Where are you based? Good luck
I asked Gaby Hobbs, my MPN specialist in Boston the following:what is the allelee burden, the percentage of hemopoietic stem cells that carry the mutation vs. the HSC that are normal? what is the VAF Burden of more than 50 percent is not good. Her reply: It is the percentage of cells sampled that have the mutation (VAF-variant allele fraction) there is no good or bad percentage.
Hi living in Uk I have never been offered Allele burden it is on my question list for next consultation. On my notes they refer to Mild disease because platelets at highest were 750 but that was prior to actual diagnosis and Bone marrow biopsy .
But then tell me I am high risk .. and must start Hydroxycarbamide asap
so I am with you on the side of confusion about categories.. let’s hope we gets some clarity soon . L
I am on the west coast of Canada and was told by my MPN specialist that the Jak2 percentage is not paid for by our medical plan as it is not deemed clinically relevant to disease treatment.
However when I had another bone marrow biopsy last fall, they did it and the next generation testing too though only a qualitative test was requested. This was a surprise to my haematologist!
Mine was lowish at 12% and I am not particularly worried, just trying to live a good life with fatigue being the most annoying feature. I am on Pegasys anyway and that may reduce allele burden over time and that might be good.
Hi, I have been diagnosed with ET 7 yrs ago and progressed toPV 3 yrs ago and on HU since PV Dx. I think that it is important to have a BMB at Dx and also AB determined at that time and probably once a yr after that. My Ab was 27% at Dx and 50% 3 yrs later and then 19.7 % after about 30 months of HU therapy. I have read every study I can find for the last 7 years. It seems to me that the evidence is growing that the lower the AB the better everything will go as far as hematological response, molecular response, and possibly morphological response. CHR, PFS and OS may be better with lowering the AB. The more mutations you have in addition to the Jak2 , the more likely for progression per my MPN specialist. These can be found thru next generation sequencing tests for mutations. Check out the Proud PV study and the Reveal study, you can find them online. I think most MPN specialists are trending to think that AB is significant, mine says that he wants to see more data before he will commit. Knowledge is power. I would recommend you pursue finding out your AB.
Hi Suenami I am in the Midlands, England and my Haematologist checked my allele burden when I was checked and diagnosed with PV. He did say the nhs do not usually do a repeat test, but he has said, he would agree to another test as he is also interested in any changes after using peginterferon .
I'm a veteran PV er who was diagnosed at age 43 and am now 63. I've been on 2 aspirin a day since turning 60 and get phlebotomy's every 3 months or so. My MPN specialist who is an expert on MPN's out of Mayo Clinic does not put emphasis on lowering the AB because it has NOT been proven to be of significance in slowing progression or improving symptoms. There are more pertinent variables that come into play which could give an indication of possible progression. In other-wards you must look at the whole picture not just focus on lowering the AB especially since it has not been proven to be of significance thus far. A BMB will give you this whole picture especially with the genetic testing.
I had a BMB last year which indicated no increased fibrosis, no other bad driver mutations and a AB of 94%. You would think with this high AB that I would be slowly progressing or demonstrate an array of symptoms!! After 20 years I am going strong and on most days feel great. I do have my bouts of fatigue but they are few and far between. My advice: Get a BMB if you haven't so you know what treatment to pursue, and stay in shape-exercise has been my medicine! Don't put too much emphasis on AB and live your life to the fullest. Best wishes!
Suenami here. Just wanted everyone to know how much I’ve appreciated every one who has taken the time to address my concerns. It’s been really helpful and put my mind at ease as to why my hematologist follows the general consensus on this AB issue. I will keep asking him what’s the latest however. Think it’s good they know we’re in the know also.
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