Interesting appointment today.

[mother2britton]

I had an interesting appointment today with my local hematologist. I'll start by saying I'm ET Calr 1. I see a specialist in Denver at UCHealth Anschutz. He is a great Dr and very knowledgeable. I also see a local hematologist/oncologist from Seattle who just moved to my local rural area who also has very good credentials and is also very knowledgeable in MPN's, we are lucky to have him. When I started my journey in 2019 my platelets were in the 500-600's and they seem to move up about 100 a year give or take. Today they are 874 so no question they are moving up and unfortunately haven't stabilized yet. I'm very fortunate to be symptom free so far. My situation is this, my specialist has the approach of "watch and wait" as long as I continue to be symptom free, Von Willebrand factor (and other bloods) in normal ranges and platelets under 1500 we have no need for cytoreduction and if that day does come we would start with HU then consider INF. So that was the plan until.... I met with my local today and he's not happy with my platelets at 874 and would like to do another draw in six weeks as well as a full NGS and BMB and discuss INF or HU for cytoreduction. he is not a believer of "watch and wait" and believes in getting on INF sooner rather than later. So I have a decision to make and I consider myself lucky to have this dilemma. I was pretty set with my specialist's approach but I also agree with my local hematologist with the sooner the better and possibly halt progression/fibrosis and start with smaller more tolerable doses for cytoreduction rather than "wait" and take large doses that I maybe intolerant too. My concern is my age (49) and how long I would be on meds, I feel the longer I can hold out the better but that theory is not relevant if I were to progress sooner (or at all) without cytoreduction. My thoughts are maybe wait and hold out until maybe 1000 and just maybe I will see them stabilize between now and then but once I am a "Millionaire" I figure it wont matter if I stabilize or not at that point. Any experience or input in the matter would be greatly appreciated. Also is there anyone that stays in that 800-1000 range and doing well?

[cmc_ufl]

INF is not for everyone. The most common treatment regimen for your case is aspirin/W&W. However, if I were in your shoes, I would see if I was a good candidate for INF. It is the only drug known to slow/stop progression of the disease. HU does not do this. Particularly for young patients, length of time having the disease is the most important risk factor for progression. In my opinion, getting on a progression-preventing treatment plan as soon as possible, as long as your individual case permits, is preferable to the “reactionary” system where treatment only begins when there is a (much more serious) problem.

[hunter5582]

There are really two issues at hand. 1. Do you need cytoreduction? 2. If so, which agent should you choose.

I think question 2 is the easiest to answer. At age 49, PEGylated Interferon would be preferred by most MPN Specialists due to the risks associated with long-term use of hydroxyurea. That is not to say that there are not risks associated with PEG-IFN, there certainly are. However, the risk/benefit profile of IFN over HU for someone your age is more favorable. Some, myself included, feel that the risk/benefit profile of PEG-IFN is better than HU for most people of all ages. Note - that is just my opinion based on the research and my own experience with both medications.

Question 1 is a bit more complex. There are differences of opinion in the MPN community about when to initiate cytoreduction. There are differences of opinion about targets for cytoreduction when it is used. The answer is not black-and-white. It really has to do with what your treatment goals are as well as your risk tolerance and preferences. Provided you are symptom free and do not have any issues that place you in the high-risk group then there is no "need" to initiate cytoreduction at this point (based on your risk profile).

There is evidence that your MPN is progressing if there is a steady upward creep in thombocytosis that is sustained over a period of several years. The plan to do a complete NGS study and BMB does make sense. You can only make valid decisions based on evidence. The complete NGS study should include a panel that would include all of the main non-driver mutations that impact MPNs. It will also include your CALR mutant allele burden, another relevant factor. The BMB will give you information about bone marrow morphology, including fibrosis. If you have prior data you will be able to assess your degree of progression.

Ultimately you will need to decide on what your treatment goals are. You will need to set priorities for these goals. We typically include:

Preventing progression of the MPN

Reducing risk of thrombosis, hemorrhage, microvascular symptoms

Controlling symptoms related to the MPN (constitutional/secondary symptoms)

Controlling systemic inflammation

Identifying the risks associated with the options to treat MPNs - deciding which risks you are more willing to take based on your priorities.

My story may be bit more complicated than yours. I was diagnosed with ET 30 years ago. it progressed to PV 8 years ago. I have had multiple surgeries in the last couple of years, including heart and brain surgery. I have a non-driver mutation, NF1. I did go on HU for a year in 2018. I could not tolerate it, experiencing toxicity even at very low doses. I opted for phlebotomy-only for a couple of years (despite now being 66) but the chronic iron deficiency became problematic. I am now taking 45mcg/week of Pegasys. It is doing an excellent job controlling the thrombocytosis/erythrocytosis. I have had no adverse effects at all. The reasons I chose PEG include better symptom control and the fact that it is our only disease modifying treatment option. I am at increased risk of progression to AML due to the NF1 mutation. I decided that it was time to improve the odds that I will not experience the progression.

This is the right decision for me based on my profile, goals, risk tolerance and preferences. Once you get all of the information together you will be able to make the right decision for yourself. It is actually a blessing that your two docs do not agree. This will give you the chance to weigh all of your options and decide what is best.

Please let us know how things go.

[katiewalsh in reply to hunter5582]

You’ve done an excellent job describing in detail the important considerations. It was nice of you to take the time to write such a long reply. Katie

[Amethist]

Hi,I can only share my story, so it’s not really advice, as only you can decide what is best for you.

At age 49 , by a chance blood test, I discovered I had high platelets around1400, confirmed ET with Jak2.

I had the blood test due to some symptoms which I was thinking menopause/ vits etc. couple of vit deficiencies revealed and in sorting those out- myself, felt a lot lot .

better . Have also changed diet to cut out sugar and processed food, eat more veg and healthy fats. Luckily I have great organic butchers near me too.

Initially Haematologist wanted me on daily blood thinners, tried this for a bit, but quickly found this wasn’t ideal for me.

Platelets have ranged from750’s to 1650’s over the years for no reason I can fathom, but they have never impacted my life in any way. Never had any clotting/ bleeding issues thankfully, which would of course be a different story.

At my last appt in Feb with the high platelets, haematologist wanted me to start on HU. From what I have researched I didn’t agree. So I went for a second opinion with an MPN specialist , explained what I was doing ( basically ½ aspirin every 3rd day, )

She reviewed my case thoroughly and at the end totally agreed with everything I was doing, and she agreed no need for any further drugs. That suits me just fine as I personally don’t want to take something where even one side effect would be a step too far. I am very active with tennis and cycling . (I checked the side effects online on drugs . com and the risk of these is just to high for me, at the moment.)

So basically, there are lots of opinions, even amongst MPN specialists.

I really recommend you take your time to do your own research on pubmed etc.

don’t rush with any decision. I found a ton of research that supported my decisions. The doctors can advise on what they think may help, but ultimately the decision is yours. Only you live in your body and know how it feels. You are also the one who will have to live with any side effects so you need to know what they are in order to make an informed choice. ( my haematologist was very skimpy with the facts so I personally don’t trust him 🥴) A few years back I decided to only see the haem once a year. If I feel fine, know that I eat well, keep fit etc, I don’t see the point of testing too often, just adds to stress levels. Obviously if I felt unwell then I would make an appt sooner .

[katiewalsh]

Hi, I think having a BMB would give you more information on which to base your decision and feel comfortable with it. If you have little to no fibrosis you might decide differently than if you have low to intermediate fibrosis. I was diagnosed after almost dying from blood clots filing both my lungs. I was around 61. Both the age & history of blood clots dictated treatment. They recommended HU for me, possibly because it’s generally tolerated by more patients. But as Hunter points out, Interferon has the potential of stopping the progression of MPNs which would have been better I think. Now, lots of folks on here have had ET Jak2+ for decades without any problems or progression. But without a BMB I don’t think you can be certain you’re ET as opposed to Primary MF. If I were in your shoes, knowing what I now know, I’d have a BMB & if it indicates a need for treatment I’d start of the pegylated Interferon. But that’s just me. But what’s important for you to remember is just because you get on a medication to bring down your platelets, you can get off of it too. So if you have unpleasant side effects you can decide to stop. I think the advice you were given to take your time to decide & not rush your decision is important. If you decide to do research be 100% certain that your source is reliable and the research is current. What was believed a few years ago may no longer be accurate. In addition to Pubmed., the MPN Foundation is an excellent source for research as are the yearly ASH conferences & Patient Power. At some point you’ll make the decision that’s best for you. And you can always tell each doctor what the other doctor recommends & ask that s/he say why that’s the wrong course of treatment. Good luck. Katie

[AndyT]

Interesting question - I was diagnosed at 47 and stayed on aspirin only throughout my 50s with counts in the 800s and 900s, before starting Pegasys as I approached 60 and counts were consistently over 1,000.

Pegasys has worked very well for me, with hardly any side effects and I now keep my counts in the 200-300s with just one 45mcg injection every four weeks. I’m retesting currently to see if my CALR mutation has reversed after 5 years on Peg - quite possibly not and even if it has, the advice may still be to stay on a low monthly dose to prevent it coming back.

I was happy to delay cytoreductive treatment as long as I could but with hindsight and knowing how easy and effective Pegasys has been I would probably have started earlier in the hope of reducing chances of fibrosis or other progression.

Good that you’re being given the two options - hope you find the right one for you!

[Emmyroos in reply to AndyT]

That is an impressive response to Peg! Well done.

[Hopetohelp]

Once my platelets were in the 800’s my haematologist wanted me to start treatment. Twice I have been told that I couldn’t have cytoreduction as the body would think it is under attack and produce more platelets. Something to think about although I am Jak2 which could be different? At your age I would definitely ask for Pegysus as first line of treatment and if it doesn’t work or it doesn’t agree with you , remembering it can be slow acting so patience needed, then consider other options. They will offer you hydroxy first as peg is very expensive. Good luck and let us know how you get on

[Whitegate]

Hi m2b - my wife's platelet count is 1180 She has no symptoms, it was a routine check that discovered the ET. Her

Haemotologist put her on 500mg HU daily and she awaits the results of blood test on 26 Nov. when he'll decide what next

Keep well and active, m2b

[mother2britton]

Such great replies/advice, thank you. I think what makes this difficult for me is the fact that I feel well (knock on wood). Any symptom burden and I don't think this would be as difficult. I am also considered to be low risk for now. As hunter mentioned, setting treatment goals would be beneficial and something I haven't done up to this point. This approach will help sort things out more clearly for me. I will be doing a lot of research in the next month, thankfully there is plenty of time.

[Tertia3]

My haematologist mentioned that there is a school of thought that believes the slowing down of the proliferation of cells in the bone marrow may also slow down the progression to fibrosis, which,I think, makes sense. Though we are all so different and most don't progress anyway.It's a minefield!Hoping that all the comments here help you with your big decision!

[Emmyroos]

I've had a very similar experience to you (at least for starters). If you haven't had a BMB in awhile, I would highly recommend one to help your doctors determine your status to treat you most effectively.

Like you, my original hematologist insisted on a 'watch and wait' approach. She diagnosed me with ET (at age 39 during my pregnancy) based on my high platelets @ 700 and JAK2+. No BMB was ever performed.

Fast forward 1.5 years later, I sought a second opinion from one of the leading MPN specialists in the world. She had an entirely different approach and insisted on starting treatment. She said that they no longer default to the watch and wait program anymore. Instead they find, treating early is better, especially for younger patients that need to manage this for a long time. My platelets were ranging 800k-1mil. She ordered a BMB immediately since one had never been performed by my previous doctor. Thank goodness (!!) because the BMB showed I had scarring and that I actually had MF, not ET.

I have since started on Pegasys (with a bit of a bumpy start) but feeling great now. My energy is back - best I have felt in years. I have so much more energy for my two babies. I don't regret starting treatment at all. I regret not getting into an MPN specialist sooner. I'm certain she saved my life or at the least added many more years to it.

Obviously, your situation is unique to you but I would recommend getting that BMB for starters and then taking it from there.

Keep us posted on your discussions and what you decide. Good luck! And ask many many questions.