Hydroxy or just aspirin for ET?

[Hombre]

I am 78 with diabetes diagnosed two years ago. Two months ago I was diagnosed with ET, CALR positive and prescribed low dose aspirin and hydroxy. Platelets were gradually increasing to around 600 and haem wants them down to less than 400. It seems from this forum that many patients, probably younger, do not go onto hydroxy until platelets are much higher. I have also read that a double dose of aspirin might be an alternative. Thoughts welcome, thank you.

[Rem31]

My platelets are rarely below 400 and can dodge around. Some time ago I asked about upping the aspirin from 75mg per day and was told absolutely not due to bleeding risk. Having had a few bumps and falls since then I’ve understood the sense of that advice.

[Hombre in reply to Rem31]

Thank you, that sounds sensible.

[hunter5582]

The recommendation for cytoreduction (with HU) is an age-based risk profile protocol. Most docs still follow this guideline to initiate cytoreduction when age >60/65. However, not all do. Some individualize the decision based on the patient's profile .

When cytoreduction is indicated, different targets are used. There is no particular evidence that reducing platelets below 400 (normal) has any particular value. Some docs now use 600 as the target when a numeric target is used.

silvermpncenter.weill.corne...

There are two first-line treatment options when cytoreduction is used. Hydroxycarbamide (hydroxyurea) and PEGylated Interferon. Some docs prefer one over the other. Some healthcare systems prefer to tart with HU since it is so much cheaper. Ultimately this decision is up to you as the patient. It is your goals, risk tolerance and preferences that should drive this decision.

mpnjournal.org/how-i-treat-...

legeforeningen.no/contentas...

Regarding anti-platelet treatment with aspirin, one low-dose aspirin/day is the standard treatment protocol. Some docs do recommend two (AM/PM), at east for some patients. There is an issue with the use of aspirin as we age. Those over age 60 tend to be at higher risk for bleeding with aspirin. Given that elevation in platelets also puts us at risk for bleeding, doubling up on the aspirin may not be indicated. (Note twin risk for thrombosis and hemorrhage with ET).

Note that the goal of treating ET or any other MPN is not to achieve numbers on a lab. The goal is to control symptoms and reduce risks. Treatment needs to be individualized based on each person's profile, their individual goals, risk tolerance and preferences. If you prefer a more conservative approach to treating the ET, that is your prerogative. Just make that decision based on understanding the risks/benefits of each of your choices.

All the best.

[Hombre in reply to hunter5582]

Thank you. Especially for the How I treat articles. It seems interferon might be a better choice than Hydroxy.

[hunter5582 in reply to Hombre]

That is the judgment that you need to make based on your goals, risk tolerance and preferences. Dr. Harrison's approach of educating the patient about the treatment options and letting the patient make the choice is clearly superior both ethically and in regards to efficacy. It is unfortunate that too many providers only offer one option to patients without explanation. This is not an acceptable way to make treatment decisions.

For what it is worth, I agree that the IFNs are a better choice than HU. That is based on my review of the literature, my goals/risk tolerance/preferences, and my own negative experience with HU. I did use HU for three separate one-year periods. It was not effective and I experienced toxicity even at very low doses. PEG_IFN has been both effective for me and I have not experienced any adverse effects.

While it is my opinion the the IFNs are a better choice than HU for most people, there are most certainly people who cannot benefit or tolerate the IFNs. There are people who believe HU is a better choice. We each need an individualized treatment approach. We each have the right and need to take responsibility for deciding which treatment approach is best. This includes the first-line treatment options like PEG and HU, second-line options like ruxolitinib and anagrelide, and the emerging treatments and clinical trials,

All the best to you as you move forward.

[EPguy in reply to hunter5582]

My 1st Hem used 600 PLT also and considered PLT values of uncertain prognostic.

In a recent post with member cmc_ufl we discussed this subject. He noted that the guidance has changed to 450PLT since the revisions of 2016. I've since been checking dates more carefully. I note the Silver mpn Center report uses a reference from 1990-1995.

Are you aware of other data on the subject? It seems many members are interested or confused about the grey areas in the 400's. I was 1000+ so by any definition there was no confusion in my case.

[Hombre in reply to EPguy]

Thank you. I don't have any other information about the desirable level of platelets.

[hunter5582 in reply to EPguy]

Most are using the current WHO Criteria of 450 to make the diagnosis. "Sustained platelet count ≥450 × 109/L. Presence of an acquired pathogenetic mutation (eg, in the JAK2, CALR or MPL genes) No other myeloid malignancy, especially polycythemia vera, primary myelofibrosis, chronic myeloid leukemia, or myelodysplastic syndrome. No reactive cause for thrombocytosis and normal iron stores."

medscape.com/answers/206697...

There is variation of what the treatment target should be when cytoreduction is indicated. Some docs want the platelet levels to ne "normal". Richard Silver and others are using 600. Spivak and others do not use a platelet numeric at all. They only focus on actual symptoms. I know that I have heard in several recent MPn presentations that there is no linear relationship between platelet levels and risk of thrombosis. The risk at higher levels is actually for hemorrhage.

I have not seen any evidence that having platelet levels below 400 has any particular value in terms of reduction in risk of thrombosis. Some people on the forum have noted a reduction in their symptoms when their platelet levels are lower. That could make some sense as cytoreductive therapy could also be affecting other things (e.g. cytokine levels). This is a very individual response to treatment. Not everyone has this same experience.

Spivak and others have discussed the challenges in diagnosing ET and the other MPNs. Many people are misdiagnosed, which in fact happened to me. One study estimated 19% of people diagnosed with ET were misdiagnosed.

mpnconnect.com/essential-th...

Hope that answers your question.

[EPguy in reply to hunter5582]

Interesting that Silver uses 600, so the experts are not all with the updated 450. That ambiguity on what matters with PLT does seem consistent.

In the 2nd reference it is clear that a BMB is worth doing esp if one has an ET Dx.

Another line gets my attn: <<Minimize the risk of acute leukemia and post-polycythemia vera MF>>

This implies there is an action that is known to affect this outcome. We've seen discussions here of <2% allele for example, but I know of no definitive guidance on an option to minimize progression.

[hunter5582 in reply to EPguy]

Sliver uses 600 as a cytoreduction target. Diagnosis would be different. He has quite a few presentations available if you want to find them.

The Website has pretty limited information. Silver is well known for his preference for IFN over HU. I expect that may be a sideways reference to the potential for IFN to prevent progression.

[mhos61 in reply to EPguy]

As far back as 2010 the BSH guidance for ET diagnosis (with regards to platelets) was a sustained platelet count of >450!

I was diagnosed in 2016 with ET and that guidance was used by my GP for haematology referral.

With regards to suggesting cytoreductive treatment I think the majority of MPN Specialists would use that target (>450) for their ‘high risk’ patients.

[Ebot]

Hi there. Hunter (as expected!) has given a very full reply above. At 78 you would generally be considered a ‘high risk’ patient on age alone and therefore drug intervention would be the normal approach.

From discussions I have had in the past with my haem team (I’m up at Guys) less might be more when it comes to aspirin. Certainly, there are no issues when it’s necessary to stop or decrease the dose due to surgery or other ongoing health concerns. I understood however, evidence indicated higher doses might have less desirable outcomes.

From everything you say, it sounds like you are receiving appropriate and conservative treatment. Are you under the care of an MPN specialist?

[Hombre in reply to Ebot]

Thank you. I'm not yet under the care of a specialist. I thought I would go along with the hydroxy for the time being and see how I get on. I appreciate that this forum advises specialist care, but don't want to insist on this just yet.

[mhos61]

Glad to hear you’re ‘going along with the hydroxy.’

Your haematologist will have made a decision to ‘advise’ cytoreductive therapy based on your cardiovascular risk.

As Ebot has stated your age alone (78) puts you in the ‘high risk’ category. Importantly, your diabetes would be an additional risk factor.

[Hombre in reply to mhos61]

Yes, thank you.

[Ebot]

MPNs are very rare diseases and (good) non specialist haematologists won’t hesitate to admit their limited knowledge and experience. I was first diagnosed by a very well regarded Professor of Haematology and was somewhat embarrassed when he said he thought I should see Prof Harrison at Guys instead of him. When I hesitated and asked if that was necessary, he said that’s what he would do if he was the patient! So, don’t be shy in asking for a referral to a specialist team even if it’s just for an annual once over.

[Hombre in reply to Ebot]

Good advice, many thanks

[jleshe447]

Hello. The treatment for my ET was low dose aspirin. Platelets were always in the 5-660 range. Dr. #1 said 'wait and watch'..........Until, just before the new year I had a femoral blood clot. It was soft tissue, broke off and it traveled down and lodged on top of my foot. Visual bruising, purple tinted toes.....I thought it was just a 'bunion'. lol. Foot Dr said NO. get to the ER NOW! I've since been treated with Xarelto, aspirin and Hydroxyurea. The vascular Dr at last visit says clot dissolved and I can discontinue Xarelto. Meanwhile, I've switched to another hematologist that is quite adamant about getting the platelets down to normal. Long story short............. Last thing you want is a clot ANYWHERE! err on the side of caution. Hang tight! Jen

[Hombre in reply to jleshe447]

Thanks Jen, good advice!