ET, JAK2+, Etc. Newly Diagnosed and Feeling Like One of the Lucky Ones

[EssThro]

Hello, Everyone. I'm one of the new kids on the block. Yes, it's the block across the Pond.

Other details about my disease: SRSF2 and del(20Q) and platelets only in the 450-500 range, some brain fog, painful erythromelalgia in my fingers at times, some fatigue, mild itching, 72 years old, taking only low-dose aspirin twice per day, despite having a TIA early last year. I am also very fortunate to have an MPN specialist.

I really want to THANK all of YOU who have posted your status, questions and answers. Your posts have helped a great deal as I searched for more information about what treatment made the most sense and what my future might look like. My specialist is very busy, so our communication has sometimes left me with partial answers. Thanks again for helping to fill in some of the blanks!

After all the facts were in place, my specialist suggested that I start Pegasys injections. Since seeing that recent studies had shown that twice/day aspirin was much better than once (similar to once/day plus HU or Pegasys???), we agreed that the medications would be primarily for control of my symptoms. My symptoms have been mild, so I opted to avoid the medications and the potential for worse side-effects. I guess I will see whether that was a good choice as time passes. For now, I will have blood tests (CBC) and an office visit every six months. Getting the follow-up plan yesterday gave me confidence that the specialist doesn't have too much concern regarding my medication decision. I can start the medication later if it becomes clear that is the better choice.

I am very fortunate to live in the southwestern US of A where it's sunny and the temperature range today is 60-90 degrees because I find that my finger issues are triggered by low temperatures and by prolonged gripping: racquets, for example. I now wear one more layer of clothing in the winter to keep warm when the temperature is below 80 and gloves when I am touching anything cold. It's strange that I don't need an extra blanket at night.

I used the calculator on sanger.ac.uk to get a customized idea of how things are likely to go from here. If you are the type who appreciates knowing, I highly recommend it. cancer.sanger.ac.uk/mpn-mul... They have disclaimers in place, but it is the only customized prognosis tool that I have heard about.

I hope there is something in here that helps someone on this forum, and good luck to you all!

[hunter5582]

Welcome to the forum. Glad you found your way here. It sounds like you have taken the time to educate yourself and understand your options, both the benefits and risks of the treatment choices we have to make. I think the most important thing is that one size does not fit all. It is also true that what is right today may change tomorrow. It also sounds like you have found a good hematologist to work with.

I have used the Sanger MPN Risk Calculator before. It is interesting from a heuristic perspective and helps puts things in context. It is just important to understand that it is a statistical projection not a prognosis. Makes for interesting thought if you do understand and certainly helps to form a useful perspective.

My now semi-retired MPN Specialist, Dr. Spivak, has a a perspective on treating ET you may find of interest. He is quite a character. While not all agree with his views, he is one of the leading MPN experts in the world.

youtube.com/watch?v=hbVr9u3...(Not working as expected?)

All the best.

[EssThro in reply to hunter5582]

Thank you, Hunter. I value your input as you certainly have done a lot more digging and digesting of the literature than I have.

I viewed Dr. Spivak's presentation earlier and the review this evening was very helpful. Thanks. Despite my age and the potential for GI issues, the statement that aspirin is the treatment of choice for erythromelalgia confirms that I should keep taking it for the foreseeable future. In general, I like his questioning of the wisdom of treating every condition as aggressively as possible.

It is also interesting that he stressed the potential to have more than one driver mutation. I believe the testing protocol I am under called for NOT testing for CALR or the other driver if JAK2 V617F is detected.

The other thing that I wonder about regarding my mutations is that, according to Sanger, it is apparently quite rare for SRSF2 or del(20q) to be observed along with JAK2 in ET patients. And having all three together is extremely rare. That combination is much more likely in MF, and possibly in AML. My BM biopsy results showed no hint of fibrosis, so that seems promising for now. My specialist said the one other positive point for Pegasys is that it may slow the potential progression to MF. My prognostic prediction from Sanger showed my chances of staying with ET, progression to MF, and transitioning to AML to be 60, 15, and 25%, respectively. I find that information to be very helpful as I make future decisions regarding my treatment.

Again, thank you for taking the time to respond and for all of your input to this board. And all the best to you as well.

[Aneliv9 in reply to EssThro]

Why my prognostic prediction doesn't shows me these percentages as yours? Also why my Risk for AML in 20 years is 30%??? I didn't know much about my mutations, so i just checked that i don't have Jak2, (all the others are unknown) and i have borderline splenomegaly. 30%???? OMG

[Aneliv9 in reply to Aneliv9]

Ok.... I just messed up my hemoglobin.. You must write it px 154 and not 15.4

[EssThro in reply to Aneliv9]

Hi, Aneliv9. I'm sorry that you saw the tool if it is giving you concern. To me it is a good thing to get an opinion, and that is all it is, on what my chances are for different outcomes over time. The numbers I mentioned are my interpretation of my chart at different times. I suggest that only those people who truly want this opinion seek it out. And then enlist the help of someone qualified to interpret it if they are not skilled in interpreting prognostic charts. Note also that these projections are primarily meant for research and possibly for clinicians who are guiding their patients.

Secondly, if you don't know your mutations, it is impossible to receive meaningful output. Based on your message, I suggest that you forget you ever heard about this tool and speak with your hematologist if you want to know your prognosis.

Again, I apologize for mentioning it.

I wish you peace and good luck.

[Aneliv9 in reply to EssThro]

I just know that i don't have Jak2 and that i have borderline splenomegaly. Isn't it enough ?

[EssThro in reply to Aneliv9]

I am not an expert, just a curious patient with a very recent diagnosis. That said, any tool is better if it has all the right inputs. I have read that our driver mutations make a significant difference. Some people have CALR, some MPL, and some have none--"triple negative."

[Aneliv9 in reply to EssThro]

I was just wondering why AML Risk at 20 years is almost double than that of MF????

[EssThro in reply to Aneliv9]

I have no expertise to apply to your question. Sorry. Apparently that result is based on the inputs you provided. I would think that you could change some inputs to find the effects of each, if you want to see what the tool is programmed to value. Good luck.

[hunter5582 in reply to EssThro]

It sounds like you have spent some time looking into what the significance of your genetic picture looks like. It is quite complex and what we learn has a lot to do with probabilities and tendencies. Understanding relative risks helps inform our decision, but does not predict the future. We have no way to know whether we will follow 1 -2 or 3 standard deviations out from the mean in terms of overall life expectancy. The numbers also don't mean quite what they appear to since most people who progress to AML will do so though MF first. People with PV are more likely tp progress to MF than people with ET. Of course, that does not factor in the non-driver mutations. That add a whole another dimension.

I am one of those who "progressed" from ET to PV. Appears to have happened about 7 years ago. Was originally diagnosed with ET about 30 years ago. I expect it was likely masked PV for quite some time. I also know that I am JAK2v617f positive with a mutant allele burden of 26%. It has only progressed 1% from 2019 to 2020. I know that I am negative for CALR and MPL since I also did a MPN Myeloid Panel last year. It did show that I am positive for NF1:c5425C>T, which I already knew as I was diagnosed with Neurofibromatosis type 1 in 1987, While NF1 is a separate disorder, the NF1 mutation is also a MPN non-driver mutation that increases my risk of progressing onto AML. That is factoring in to my consideration for treatment at this point and along with some changes in symptoms.

Wishing you all the best as you are making decisions regarding your own treatment.

[Aneliv9 in reply to hunter5582]

Hello. Can i ask you with all my respect how do you cope with the thought of POSSIBILITY of your PV progress to AML? Isn't frightening for you? Also what treatment do you have in order to Improve your chances of not progressing to AML? have TN ET and i am very afraid,so i try to understand others people view. Also i think that this prediction programm, must have include pre-PMF patients in the ET sample.

[hunter5582 in reply to Aneliv9]

I have multiple strategies to deal with knowing I have a risk of progression into MF/AML.

Knowledge = power - Part of what can make this hard is feeling powerless. Knowledge is power. Educating myself empowers me to make good decisions and deal effectively with the MPN and other medical issues I face.

Support - I have people I can talk to about what is going on with the MPN. This forum would be a big part of that. I get a lot of support here. Supporting others in their journey with a MPN helps me as well. We really are stronger together.

Faith - I am a person of faith. I say the Serenity Prayer every day and embrace what it means. Lord grant me Serenity to accept the things I cannot change, Courage to change what I can, and Wisdom to know the difference... Moreover, I do not fear death. Something better awaits me. I am not in any hurry to exit this plane of existence as I have a lot left to do, people who I love, and a good life to live. I plan to embrace life for as long as I can maintain a good quality of life then embrace death as a blessing when it is my time.

Of course there is fear. In the last several years I have dealt with the progression of the ET into PV, heart surgery, brain surgery to remove a tumor, and more. I just cannot let my fear overwhelm me. You may have seen me cite this quote before, but this philosophy is one I embrace. "I must not fear. Fear is the mind-killer. Fear is the little-death that brings total obliteration. I will face my fear. I will permit it to pass over me and through me. And when it has gone past, I will turn the inner eye to see its path. Where the fear has gone, there will be nothing. Only I will remain." Frank Herbert, Dune.

Prevention of the progression of the MPN is a very challenging question with an answer that is an area of emerging understanding. The short answer for me is: control systemic inflammation, avoid exposure to toxins/carcinogens/mutagens, maintain good overall diet/health. The emerging research on the potential for PEGylated Interferon to prolong MF/AML free survival is very promising. The research on PTG-300 and other newer agents to treat MPNs is also very promising. I may well move n this direction in my own treatment. This is a decision I will be making with my care team in the near future, based on the science and my preferences and risk tolerance.

Hope that answers your question. All the best to you.

[Aneliv9 in reply to hunter5582]

Thank you for taking the time answering my question. What are the chances of your PV progress to AML?Also I didn't know that peg interferon prolongs AND AML free survival except MF. I will also look right now PTG-300

[hunter5582 in reply to Aneliv9]

Most people who progress to AML progress through MF. It is rare to go directly to AML from PV. You will see very broad numbers in terms of risk of progression to MF/AML tp be in the neighborhood of 20%. It is a fuzzy number since there is overlap. Some people progress to MF, but not to AML. I have seen various numbers connected to AML progression, but 8% is what I recall as a pretty round estimate. Just as a side note, you may also seen this referred to as the blast phase of PV.

There is not a numeric indicator for how much my risk is increased because of the NF1. It is just known that a higher percentage of people who do progress to AML are positive for NF1 too.

There is a lot of research out there regarding PEG-IFN and prognosis. It is why it there is so much interest in it. Our friend Manouche has posted many links to this data. Silver, Hans Hasselback, Kilajean and others have a lot of data out there now. It is definately worth reading. Besremi (ropegylated interferon) is particularly promising since it seems to be easier to tolerate.

PTG-300 is in clinical trials. It is a hepcidin mimetic. It would not be expected to affect the MPN progression, but does help to control erythropoiesis without phlebotomies. Hepcidin is one of the regulators of iron metabolism. PTG-300 allows your iron levels to come up, but does not let your body use the iron to make RBCs. It is an improvement in quality of life since iron deficiency does have side effects.

Hope that helps.

[Aneliv9 in reply to hunter5582]

Thank you again for your answer,it was very informative. I have now the "big" question that haunts me this month.. This 8% for AML , is the percentage of risk in 20 years time?? I have ET ( from my blood counts it seems as if i have it since 17 years old -so 20 years at least until today) and i try to find out what is the risk for my situation.. 20 years have already passed, so i don't know the long term ( 40-50 years) risk..

I have also been very stressed about progression, cause it looks like the more I live the ,the most likely to progress.. So I can't cope with these thoughts,i am.very worried. (Sorry for my English,i am from Europe)

[hunter5582 in reply to Aneliv9]

For estimating purposes, consider the 8% as your lifetime risk of progressing to AML. The studies do not go out 40-50 years so there is no hard data on that. That is also a very fuzzy number with people from various risk bands included. The issues and questions that matter are: What is the status of your mutant allele burden? Do you have any non-driver mutations present? Is there a progression in MPN symptoms? What is your lifestyle, diet, and other health issues? These factors will tell you about your relative risk level, but not give you an exact number.

When it come to risk - less is better, My approach is to control what I can and let go of the rest. I am staying up-to-date on my treatment options and assume my treatment plan will need to change over time. I opt for the best available treatment at any given point in time with the goal of first preserving my quality of life and second extending life (only when quality of life is preserved). I seek to make all my decisions based on facts, not fear.

I really do believe in focusing on living a good life and spend my energy on making that happen. I have concerns about progression of the MPN. It would be foolish to ignore it. I just do what I can to give myself the best chance possible and do not worry about things I cannot control.

All the best.

[Aneliv9 in reply to hunter5582]

You have such a nice and strong mindset. I wish i could achieve this to. It was encouraging though to read your reply! So 8% is a 20 years "lifetime" Risk as far as I understand. It applies on ET also, or is only for PV?

As far as the video you uploaded, i have one more question!

Because of my English, i can't clarify the spot that talks about Jak2 ET with high hematocrit vs Jak2 PV: Does he mean that these two entities are the same and that faulty doctors believe that high hematocrit Jak2 ET is ET?? I can't get it..

Also when he mentions that "some patients ask if ET is cancer, no is a clonal disorder that COULD become a cancer" is he refers to PV???? Cause he talks only about ET and PV..

[hunter5582 in reply to Aneliv9]

Dr. Spivak prefers to look at ET as a clonal disorder rather than a true cancer. Actually a number of other people in the MPN world agree. Technically, ET is a "neoplasm" and can be classified as a "cancer." The way I look at it is that it is cancer with a little "c" not Cancer with a big "C."

The answer about ET vs PV is a bit complicated. Add to to it the existence of masked PV that is often misdiagnosed at ET. Some view ET and PV as very distinct disorders. Others view it more as a continuum. If you want to learn more, suggest Dr. Spivak's article on MPNs.

legeforeningen.no/contentas...

If you are interested, Dr. Spivak has an excellent article on treating PV. I do not have a link as it is not posted on the Internet, but he did give me a PDF copy I can share if you are interested. Message me if you are interested.

The risks of ET progressing exist, but are lower than PV. The risks of MF progressing are higher than PV as I understand it.

Regarding mindset, it is something you can develop. I went through a very hard time back in 2013 that I did not manage well. I learned my lesson and changed how I deal with stressors. The whole list of coping strategies is a bit longer, but a really good starting point is a book called Make Your Bed by Adm. William McRaven. it may seem an odd recommendation to read about the philosophy of a Navy Seal (a warrior) but it is highly relevant to us. We are fighting our own war with MPNs. Some basic warrior philosophy works for me in this context. The book really is about overcoming hardship and living a successful life.

All the best.

[Aneliv9 in reply to hunter5582]

All of these are interesting and i will definitely look for the book. I have ET but my hematocrit and hematocrit seem to rise very slowly these past 10 years. My bone marrow has trilinear proliferation and my erythropoietin was normal. I DON'T have the Jak2 mutation (but i just did the classical plain blood test), so is it possible to have masked PV and my heam has missed it out?? I understand that quantity of alleles is what makes the difference between ET and PV, maybe ET is the right diagnosis? I will also read the link that you send me! Thank you again, you are very kind with me and my questions!

[cmc_ufl in reply to Aneliv9]

Hi Aneliv,

I know we have talked about your situation before. As I recall, you were only tested for JAK2 V617F. You were not tested for JAK2 exon 12, CALR, or MPL, right?

Again, I highly recommend you ask to have yourself tested, at a minimum, for the JAK2 exon 12 mutation, preferably also for CALR and MPL, ideally also to have a myeloid panel done looking at all the non-driver mutations.

I hope you are doing well.

[hunter5582 in reply to Aneliv9]

cmc_ufl is correct. If you were not checked for CALR and MPL you should be. That is the standard protocol for anyone with ET and JAK2 negative. I seem to recall you were not sure if CALR and MPL had been checked.

Given what your concerns are, I would get a full MPN Myeloid Panel done to look for all three driver mutations and multiple non-driver mutations. Here is an example of that sort of panel.

files.labcorp.com/labcorp-d... . Not sure what is available in your healthcare system, but likely this or something similar can be done.

It is possible your hematologist has missed something. My old hematologist did. Given the lack of the JAK2 mutation, masked PV is much less likely, but still possible. Given that your BMB shows trilineage proliferation, I would certainly be looking for more information. It seems quite possible that you just have a unique presentation of ET. There is still a lot to learn about MPNs.

Hope you get answers to all of your questions,

[EssThro in reply to hunter5582]

Hunter, I commend you for jumping in and becoming such a resource and comfort to Aneliv and the rest of us. Thank you!

[hunter5582 in reply to EssThro]

Thank you for your kind words. I have also been through a lot in the last couple of years. This forum has been an important part of my support system. We truly are stronger together.

[Aneliv9 in reply to hunter5582]

I believe because of my Bone marrow morphology that calr or mpl mutations are not possible,cause their morphology is very different, the same for blood counts. My morphology looks like Jak2 mutation and because i have present of hemosiderin, looks like ET. PV doesn't have hemosiderin,but i really keep thinking about it.. I am also afraid to have the full myeloid panel,cause if a suspicious mutation exists, unfortunately I don't t how i could handle it . I have a very big problem with dealing with my diagnosis. Every day i am afraid and feeling insecure about my future. Its like i have convince my self that progression is inevitable

[hunter5582 in reply to Aneliv9]

MPNs are not monolithic diseases. There can be unique presentations that do not fit into the norm of how others present. You may well be one of those whose presentation is more unique.

Regarding the additional genetic testing - I would suggest that you will have to decide which is worse, fear of the known or fear of the unknown. There is no right or wrong answer to this question. It is something we each have to decide for ourselves. Having more information helps me feel more in control and better able to make decisions. You will have to decide what will work best for you.

The reality for any of us is that our MPN may progress or it may stay stable for many years. For myself, I choose to focus on living a good life and doing what I can to improve my chances to preserve a high-quality of life. Ultimately, it is about embracing what the Serenity Prayer asks for - Serenity of accept the things I cannot change; Courage to change what I can; Wisdom to know the difference.

Wishing you all three - serenity, courage, and wisdom.

[EssThro in reply to Aneliv9]

HI, Aneliv. I am sorry to hear that you have that level of distress. Have you told your primary care physician how you are feeling? Dealing with the emotional reactions can be a major part of patient care. I hope s/he can work with you to decide what diagnostic and prognostic information is best for you to receive and get you in touch with a good counselor to guide you through your process. In the meantime, I hope that some of Hunter's input and suggestions are helpful. The serenity prayer he mentioned is very helpful for me. And remember that not much in life is certain and, for example, if a person has a 20% chance of something bad happening, there is an 80% chance that it won't. I know it can be hard, but try to focus on the positive. If we can appreciate what we have and truly enjoy those blessings, we can squeeze out a lot of the other thoughts.

I hope some of this helps.

Best to you!