I am jak 2 positive calr negative person who has polycythemia Vera as well as GCA.
Was diagnosed 2 years ago when I had abnormally high platelet count and hemoglobin and am on HU since then ,500 mg everyday of the week. Initially did 3-4 phlebotomies.
Currently all blood parameters are perfect.
After listening to a lot of expert views it seems there is is wisdom in taking interferon earlier than later rather than hang onto Hydroxyurea/Hydrea.
Have the following questions and doubts
Should I switch from HU to interferon though the blood tests are all normal.
What type of interferon is best
Has anyone been forced to return to HU because interferon did not suit them?
Are there any here who had remission after using interferon
How long is it best to use interferon ?
Thank you in advance ....... This community here is just too good to be true almost .
I could not have fought back my condition without the support I got here.
Regards.
Written by
Iwillwin123
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Boy is that ever a really complicated set of questions! Many of the answers are "it depends." Factors like age, adverse effect history, risk tolerance, and your preferences all bear on the answers to your questions.
I gather you must have been tracking the research on the use of interferons in treating PV and the emerging consensus that is is a superior form of treatment. There are good reasons to think this is so. Risk/benefit analysis comparing HU to IFN as well as the possibility of both hematologic and molecular remission with IFN is quite promising. That is not to say that IFN is without risk - there certainly can be adverse effects with it too.
I am actually in process of making the same decision. Considering switching from phlebotomy-only to either Besremi (ropegylated interferon) or PTG-300 (hepcidin mimetic). I am HU-intolerant so would not consider going back on it. I would also consider Jakafi (ruxolitinib), but as a second-tier choice for me.
So here is my thinking.
Considering clinical trial of PTG-300. Research is very promising for control of erythrocytosis while allowing iron levels to be higher. I am having issues with the chronic iron deficiency - including increased thombocytosis.
Considering Besremi. Word it that the FDA way soon approve it in the USA. Research on earlier use of IFN in treating low-risk PV is very promising. At age 65 and positive for the NF1 mutation as well as JAK2 - I am at higher risk for progression to AML. Besremi is supposed to be the easiest IFN to tolerate and has a better risk/benefit profile.
So no black-and-white answers here. But a lot to think about. I hope some others with experience with the interferons will weigh in, especially those who have used Besremi.
Thankyou for that very comprehensive opinion . I follow your opinions here closely Would there be somewhere I could get a proper understanding of what make a PV jak 2 positive person more prone to MF or AML ? I mean I know there is no exact risk formula but at least to judge whether I am high risk or not in the first place ?
There are factors known to correlate with increased risk of progression into MF or AML.
The presence of non-driver mutations known to be related to progression.
"Non-driver mutations and JAK2V617F allele burden have been involved in progression to myelofibrosis (MF) or acute myeloid leukemia (AML) in patients with polycythemia vera (PV) and essential thrombocythemia (ET)"
Only gave on citation. there is quite a bit out there on this topic at this point. In my view, this IS one of the things that is worth checking for. In fact, I would say it should be standard clinical practice. The are a number of test panels for this. I recently did the Inelligen MPN Myeloid Panel. It was covered by m y insurance.
The progression of JAK2 mutant allele burden (MAB).
No quotes here. This is a topic with a lot of research and something that comes up a lot on the forum. JAK2 mutated hemopoietic stem cells (HSCs) have a clonal advantage over the Wild-type HSCs. Over time MAB will tend to progress. The rate of progression can vary widely. Whenever there is a change in disease status, this is something that should be checked. FYI - the Intelligen MPN Myeloid Panel includes MAB.
The degree to which the JAK2 mutation is heterozygous vs homozygous (one side vs both sides of the gene pair).
"JAK2 617V>F mutation occurs in a homozygous state in 25% to 30% of patients with polycythemia vera (PV) and 2% to 4% with essential thrombocythemia (ET). ... JAK2 617V>F homozygosity associated with more frequent evolution into secondary myelofibrosis in both PV and ET"
Only listed one citation. You can look for more. Really understanding this requires a bit more knowledge of genetics and the molecular biology of MPNs. My understanding = the KISS level. 🙂 Not sure about having this tested for. I believe it is uncommon outside of a research setting. I have not bothered with it.
Exposure to toxins - mutagens, carcinogens, leukemogens.
The are a number of toxins (environmental, in the food stream, medications, etc.) that increase the risk of disease progression. Quite a list actually. The best we can do is make good choices and avoid exposing ourselves to things that increase our risks.
I did find this presentation after a quick look on this topic. It is KISS, but has some good information.
Is there a list of critical mutagens, carcinogens, and leukemogens to absolutely avoid for MPN patients? I try to minimize exposure to these toxins, but here in CA, the Prop 65 list is quite extensive, and I struggle to maintain a balance between constantly taking caution and reclaiming the relatively worry-free life I had before my diagnosis.
There is no list that I am aware of. This requires a bit of just using good judgement. For heaven's sake, don't use tobacco. Limit exposure to sources in the food stream that expose you to synthetic hormones, xeno-estrogens, antibiotics, and pesticides. Limit exposure to mercury (found in certain seafoods). I expect you know the rest of the list.
Pay attention to the adverse effects of certain medications that are known mutagens/carcinogens/leukemogens. Note that you have to weigh the risks vs benefits of ALL medications. Some meds are worth the risk. You have to look at all of your options then use your best judgement.
MPN patients have an increased risk of neoplasms due to the deregulation of the JAK-STAT pathway. There are also things that would make progression of the MPN more likely. My take on this is to heed the Serenity Prayer. Grant me Serenity to accept the things I cannot change. Courage to change the things I can. Wisdom to know the difference. My approach is to limit my exposure to toxins where I can without being obsessive about it. I do believe that worrying is "carcinogenic." Therefore, I do the best I can to take care of myself and let go of the rest. It is all about finding a good balance that works for you.
Will go through the presentation . The big question I will find hard to answer is that currently after taking HU for nearly 2 years , the blood reports are excellent ..... so any doc will ask me why I want to rock the boat ...... I guess the main thing is that future prevention of fibrosis in bone marrow is what hopefully interferon will do for me ....... I hope the doc sees the point .
The bottom line is that your decision needs to be based on your assessment of the risks and benefits of each of your choices. There are also your treatment priorities. If prevention of disease progression/possible molecular remission is your priority, then PEG-IFN is a better choice. HU is currently controlling your lab numbers. You did not indicate how well it controls actual symptoms or whether you are tolerating HU, but am assuming you would have mentioned it if it was causing significant problems. If you tolerate HU and it controls actual symptoms/risks, then that supports its use.
You also have to consider the side effects/risks. HU is carcinogenic, mutagenic and potentially leukemogenic. Note that the leukemogenic potential is debated, but it appears there is increased risk when used long-term. Many feel the benefits outweigh the risks. PEG-IFN has risks too. It can cause Stevens-Johnson Syndrome, thyroid issues, and autoimmune disorders. Since you have GCA, that latter might be a specific concern. There seems to be an emerging consensus that the risk/benefit analysis for PEG-IFN is better for most people with PV.
There is not a black-and-white issue here. This is about making a judgment based on your unique presentation of the MPN and related medical issues, your treatment priorities, and your risk tolerance. Hopefully your hematologist will listen to you. Suggest you be very clear about your treatment priorities and what you are/are not willing to risk. Your preferences matter!
You have summed up my conundrum so perfectly ....... PV and GCA has put me into a rather tough corner - wonder if I should try Ropeg- interferon and see what happens - and if it leads to any concerns then quickly rewind back to HU. I have no side effects of HU at all and it has controlled my numbers well - the standard question I know I will be asked is - why are you rocking the boat ??? I am on steroid to control GCA and HU to control PV .
I sometimes Suspect to that PV led to GCA - in which case I ought to gun fir the PV first ...... I am told GCA burns itself out anyway after 3-4 yrs.
So PV is the more long - term monster maybe ........
Well you brought up another compilated issue! MPNs are at the core inflammatory disorders. Deregulation of the JAK-STAT pathway causes your body to make too many inflammatory cytokines. Don't know that PV "caused" the GCA, but I would bet it makes it worse. And vice versa. The body is an integrated system.
Just because this is not complicated enough, I do wonder about Jakafi in your situation. Since it is a JAK-inhibitor, it might be a choice worth considering. Not at all certain about that, but would ask about that choice too.
Yes that is indeed such a great thought . In fact read somewhere about a combination therapy approach of Jakafi ( Ruxolitinib) and pegylsted interferon - am looking for those who have had such a combo therapy - the resins for taking it and the outcome experiences .
Another suggestion - get a free ePocrates account. There are great drug monographs and a really nice drug interaction tool. epocrates.com/
Using prednisone as the steroid and assuming low-dose aspirin, here are the listed interactions (which hopefully you were advised of).
Actemra (tocilizumab) + HU + prednisone + low-dose aspirin
Monitor/Modify Tx
tocilizumab + hydroxyurea
monitor CBC: combo may incr. risk of myelosuppression, serious infection (additive effects)
Monitor/Modify Tx
tocilizumab + prednisone
monitor bleeding s/sx: combo may incr. risk of serious infection, GI ulceration, bleeding, perforation (additive effects)
Monitor/Modify Tx
tocilizumab + aspirin
monitor bleeding s/sx: combo may incr. risk of GI ulceration, perforation, bleeding, incl. life-threatening (additive effects)
Monitor/Modify Tx
prednisone + aspirin
monitor bleeding s/sx: combo may incr. risk of GI ulceration, perforation, bleeding, incl. life-threatening; may decr. levels of aspirin, efficacy (additive effects; incr. clearance)
Caution Advised
hydroxyurea + prednisone
caution advised: combo may incr. risk of serious infection (additive effects)
Additional Considerations
tocilizumab in Actemra
caution advised w/ narrow therapeutic index drugs; chronic inflammatory conditions may alter metabolic enzyme formation; tx w/ immune modulators may reverse this effect, resulting in altered levels of concomitant drugs
The meds we take DO interact with each other. Presumably the docs take that into account in dosing and monitoring, but it is not safe to assume this is the case. I have had docs tell me that they cannot keep track of all of the interactions - which is why they rely on software like ePocrates.
Since you are considering changes to medications and the impact it may have, you may want to look at the different potential drug interactions. (Note: this database appears to be limited to drug approved in the USA) You can use Pegasys and Jakafi to see what those interactions look like with the rest of what you take.
I do not take ANYTHING without checking for interactions. (e.g. fish oil + aspirin is contraindicated) - Unfortunately many of the supplements are not in the ePocrates database.
Do check out the interactions with Pegasys and Jakafi and the other meds you take. Some things are similar. Other things are not. We can only make good decisions when we consider all of the information we need.
The combination approach is out in the literature. The results are quite promising. One example --ncbi.nlm.nih.gov/pmc/articl... .
Not sure that this approach is seen much in clinical practice. I would expect most docs would be hesitant to initiate it unless the patient was not responding adequately to monotherapy. Like you, I would be most interested to hear from anyone who has tried the combination therapy.
I believe there was one person here who was on combination therapy - of jakafi and interferon . Hope he reads and responds -....... I must try and search to locate him here .
What should be an ideal gene panel tested fir mutations for Polycythemia Vera . I have done jak 2 and CALR . Which other genes should be included in the panel ? TIA
Checked the link and it works. We run into the sometimes jumping across the pond. Try this one instead. It is actually a better description in that is outlines the set of these NGS panels. The lab tech actually ordered the wrong panel the first time they ran it. You would want the MPN Panel. files.labcorp.com/labcorp-d...
Shoot me a message if this link does not work and I will get you the PDF version of the file.
Did you request for the Intelligen Myeloid Panel or was it recommended by your hematologist? It seems as if the results can help with guidance on optimal treatment options? I am wondering if this can be done in lieu of BMB to predict the progression of our conditions.
I requested the panel. I did some research when it became clear that my thrombocytosis was running higher than usual. Was concerned about possible progression of the PV so wanted to look at the JAK2 Mutant Allele Burden. Decided to check on the entire MPN non-driver status as well to better determine what my status was. My hematologist and the MPN Specialist both did not feel a BMB was warranted. There is no sign of disease progression based on the tests I did. JAK2 MAB had only progressed 1% in 1 year. I am negative for all non-driver mutations except for NF1:c5425C>T, which I already knew that I had.
The MPN Myeloid Panel is not something to be done in lieu of a BMB. It is often done at the same time, but can also be done with a blood sample. The two tests are looking at different points of data. The BMB is looking at bone marrow morphology (fibrosis, megakaryocytes, etc.). The MPN Myeloid Panel is a Next Generation Sequencing genetic test, looking for the presence of both driver and non-driver mutations. Both sets of data are important. Which tests you do are based on what information you are looking for.
I have never done a BMB. All of my hematologists/MPN Specialists have not felt it was needed in 30 years of having a MPN. There are certainly MPN Specialists who would have done one a long time ago. I will do one just as soon as my care team says it is indicated. Basically, that will be when it is clear that there is a change in disease state. I am sure they would do one if I pushed the issue, but I am comfortable waiting.
Unfortunately, many hematologists have very little experience with MPNs. That is why consultation with a MPN Specialist is so important. It is also why educating ourselves is also important. That allows us to be effective advocates for our own care.
Well you have found THE place to enable yourself . As you can see , most of the folks here are very erudite and are quick to reach out with their knowledge, help and comments. I can say I have forged ahead with confidence ONLY because of this group, and never fail to check back when in doubt or trouble.
I’ve just googled GCA. It sounds debilitating. Regarding your questions I haven’t taken interferon. I hope you get answers. They in turn will hopefully help you discuss your queries with your heamo.
Yes GCA is a tough adversary . Coupled with PV just makes things more complicated. I plan to discuss with the hemo but I find that talking to people here is extremely enabling and more so before talking to the docs
Hi, i was on interferon for 11 years, mild side affects, then went onto peg interferon, from July i have been just on asprin because bloods were fine, platelets 200, only recently platelets climbing around 400 at present, so there keeping a close check repeat bloods every four weeks, i did have T IA a's when platelets were 800, but i have been lucky that interferon works for me.
The choice to never try Hydrea - was it because of young age ? I mean were you just following doctors advice or was it a personal choice ? If yes why ? And what were the side effects before peg interferon ? Sorry too many questions .......
My hematologist said at the time, because i had a Tia's and a bleed in the bowl, and my platelets were only around the 800 range,which is quite low to start treatment, but everyone is different. I started on interferon alpha 2b, mild side affects a little tired and felt like i had a cold, but after a few weeks felt a lot better.after many years the hospital could not get the interferon alpha so i was then put on peg interferon, platelets went to low, so had a bit of a break since july.
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Would there be somewhere I could get a proper understanding of what make a PV jak 2 positive person more prone to MF or AML ? I mean I know there is no exact risk formula but at least to judge whether I am high risk or not in the first place ? 
ET: Changing from HU to Jakafi or an Interferon treatment
Anyone on Interferon for 5 years or more??
Severe Tinnitus : hydroxycarbamide vs interferon
