I have had ET, Jak2+ for 5-1/2 years and my platelets have been rising the past 1-1/2 years above normal range. Recently, I had routine blood work ordered by my GP and the results showed an almost 200 thousand increase in platelets since May from 629 to 805. I messaged my MPN specialist with my concern. I received a reply and was told she was more concerned that my Hematocrit and Hemoglobin increased from 43.1 to 46.4 and 14.8 to 15.6 respectively from May to August. I have been taking 500 mg Hydroxy 4 days a week and 1000mg 3 days a week. I am told now to increase to 1000mg 7 days a week. I am to repeat blood work in a month and prayerfully the numbers will come down. But, my question is is it possible I have progressed from ET to PV? Or, is the Hydroxyurea no longer effective and I should consider an alternate therapy? Appreciate your thoughts
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It sounds like your MPN Specialist is right on track with what is going on.
When I progressed from ET to PV, my old hematologist missed it. I was improperly treated for nearly 5 years before the progression was caught and addressed. That is when I realized i needed to consult with a MPN Specialist rather than just a regular hematologist. I also realized that I would need to better educate myself to ensure I received the care I need.
It is common for PLT to vary by as much as 100K in a single day in response to what is going on in the body. My PLT often varied by 200K for over 30 years with a MPN. While the progression of the thrombocytosis is something to be concerned about, the progression in HCT/HGB is a greater concern; more so given that you are seeing progression while taking hydroxycarbamide.
You are correct to wonder if the ET has progressed to PV. You are also correct the wonder whether you are refractory to the hydroxycarbamide. Both things happened to me. I progressed to PV and the HU stopped working and had terrible side effects.
The good news for me is that there is something that can be done about this. I ultimately switched to the interferons (Pegasys then Besremi). The IFNs have been far more effective and much easier to tolerate than HU. The IFNs have kept me in a complete hematologic response and my allele burden has reduced from 38% to 9%. I am hopeful for achieving a molecular remission. I actually feel better now than I did 10 years ago.
Know that if you have progressed to PV, you can manage it. If you are becoming refractory to hydroxycarbamide, you have other options. MPN treatment options have improved a lot in recent years. Properly managed, most people with ET or PV can expect to live normal lifespans.
It sounds like you have a MPN Specialist who i right on top of things. Have confidence that regardless of your current status, you can find an effective way to manage it.
Thank you, Hunter, for your encouraging and informative reply. We will see in a month if numbers change. I will not have an appt with MPN specialist until November unless the results of my blood work in September deems an earlier visit where I will ask if she feels I have progressed to PV. In May I gave a sputum sample to test allele burden to a medical student working with my MPN specialist but I was told by her RN that they have not processed those samples as of yet due to low priority. Again, appreciate your thorough reply
For myself, my HCT and HGB were elevated for >10 years but my blood counts stayed normal, and the only treatment recommended was periodic blood donation.
But in 4/22, my RBC went up above normal for the 1st time, and then about a month later, all my counts were sky high, which prompted treatment w/ HU, which I didn't tolerate.
Now that I have been on Besremi for just about a year, my HCT is staying pretty close to goal [45% or <], and although my RBC just normalized, my WBC and Platelets normalized around 4-6 months into treatment.
Best of luck and remember, it's the long haul that matters most.
As usual, we need to be clear this drug INF doesn’t “usually” slow or stop progression, I don’t know why you keep posting it again and again. The reality is it might slow progression for a minority in the opinion of some docs, other expert docs such as Clair Harrison has said recently none of the current drugs affect progression. To say it “usually”does is just irresponsible and inaccurate. It’s maybe the best drug for us of the poor choice we have for those who can tolerate it, but we have to be realistic.
“The excess deaths from progression to myelofibrosis can be prevented with interferon. In fact patients treated with interferon had a normal life expectancy across a 30 year duration of follow up.” youtu.be/W3JJBS645c4
I am being notified that you are answering my question when in actuality you are having a disagreement with monarch5000. I am disappointed that neither of you have addressed whether you think I have progressed to PV:/ Rather, you have called each other to a duel Please have that conversation separately apart from my question.
I'm not a doctor, but I'd say that you probably have progressed to PV since your RBC and HGB have been rising despite taking hydroxyurea. An inexpensive erythropoietin (EPO) blood test can help verify PV. A low or low normal test result number (2-5) strongly suggests PV. Here’s a look at what we know about the three main treatment options for PV:
The Silver MPN Center in New York City treated 470 PV patients over a 30 year period and this is how their outcomes differed depending on their treatment:
20 years after diagnosis:
95% of PV patients who had been treated with interferon were still alive 15% of them had progressed to post PV myelofibrosis
63% of PV patients who had been treated with hydroxyurea were still alive 41% of them had progressed to post PV myelofibrosis.
57% of PV patients who had been treated with phlebotomy-only were still alive 49% of them had progressed to post PV myelofibrosis.
I think you are being informed we have replied to your post or someone elses post not that we have answered your question. I am sorry you are disappointed neither of us have adressed your question re whether you have progressed, but if you read the second part of your question it says" is the Hydroxyurea no longer effective and I should consider an alternate therapy? Appreciate your thoughts:)" , well we gave you our thoughts , Monarch was pro Inf and I think what he posted is incorrect and if you are wise you should pay attention to that if you are considering changing treatment because Inf is probably the most likely alternative. I think calling it a duel is somewhat dramatic and not very useful , its actually a debate about treatment option which is what you asked about. This is a public forum and I dont think you have the option to ask us to do anything such as "having that conversation seperately". Even if you are not aware of it that conversation is an answer to part of your question and a important one. If we have not answered whether you have progressed or not it might be because we dont know, if you have been on here any time you will note I do answer a lot of questions but only if I have something useful to add, nobody on here knows if you have progressed, we dont know all your history or labs and we are not doctors and we are not obligated to answer that no matter how annoyed you may get about it. You will get more out of this forum by utilising a little more politeness.
Complete molecular remission in a polycythaemia vera patient 12 years after discontinuation of interferon-alpha
. Murphy, S. McPherson, S. LangabeerPublished 1 February 2011Medicine, Biology. Annals of Hematology
A patient with PV is described who is in complete haematological and molecular remission despite stopping IFN-alpha 12 years ago, and it is hypothesise that IFn-alpha caused a sufficient suppression of the JAK2 V617F-bearing clone to subsequently allow full expansion of normal haem atopoietic elements.
Abstract
Dear Editor, We read with interest the recent report of a sustained molecular remission of 12 years ’ follow-up after discontinuation of interferon-alpha-2b (IFN-alpha) in a patient with polycythemia vera (PV) [1]. IFN-alpha can produce regression of splenomegaly and control of peripheral blood counts in patients with myeloproliferative disorders for prolonged periods even after discontinuation [2]. Recently, the JAK2 V617F mutation has become a reliable disease marker in most cases of PV with detection and quantitation of mutated JAK2 alleles potentially useful in monitoring the effects of treatments such as IFN–alpha [3, 4] and a plethora of novel JAK2 inhibitors [5]. We describe a patient with PV who is in complete haematological and molecular remission despite stopping IFN-alpha 12 years ago. A 19-year-old male presented in November 1990 with haemoglobin (Hb) 6.4 g/dl, red cell count 3.94×10/l, MCV 52 fl, platelet count 491×10/l and with a normal white cell count and differential. He had a 4-cm palpable spleen. Trephine biopsy was hypercellular with increased erythropoiesis, myelopoiesis and megakaryopoiesis but no increase in reticulin staining. Bone marrow cytogenetics was normal. He was treated with oral iron, which was discontinued in April 1991 when Hb increased to 18.2 g/dl. An increase in red cell mass of 50.2 ml/kg confirmed a diagnosis of PV and was controlled by intermittent venesection until February 1993, when he started treatment with IFN-alpha-2b at 3 million units subcutaneously three times weekly. Complete blood counts have subsequently remained in normal range, whilst the patient’s spleen has remained impalpable since October 1994. Repeat BMA and trephine biopsy in September 1997, whilst showing erythroid hyperplasia and increased numbers of megakaryocytes, were much less hypercellular than at diagnosis. In November 1997, IFNalpha was discontinued because of fatigue. In October 2009, the JAK2 V617F mutation was undetected in DNA extracted from whole peripheral blood using a previously described allele-specific PCR technique [6]. This methodology is capable of detecting a heterozygous mutation in 2% of total cells from either peripheral blood or bone marrow. As the patient remained completely asymptomatic with normal physical examination and normal complete blood count and as the JAK2 V617F allele burden is reportedly equivalent in peripheral blood and bone marrow [7], bone marrow examination was not repeated. DNA extracted from archival bone marrow aspirate slides from November 1990 and September 1997 were both subsequently found to harbour the JAK2 V617F mutation. In two recently reported phase two studies of peg-IFNalpha-2a in PV patients, complete molecular remissions were obtained in 7/26 (27%) of responding patients and in 14% of 35 evaluable patients [3, 4]. In this case, peripheral blood taken 12 years after stopping a 4-year course of IFNalpha displayed a complete molecular remission according to consensus guidelines [8]. In our patient, it is noteworthy that a bone marrow sample in 1997 just prior to IFN-alpha discontinuation was still positive for the JAK2 V617F mutation, yet a peripheral blood sample 12 years later was negative for this mutation. Although remission unrelated to treatment remains a possibility [9], we hypothesise that IFN-alpha caused a sufficient suppression of the JAK2 V617F-bearing clone to subsequently allow full expansion of normal haematopoietic elements. Although quantitation P. T. Murphy (*) Department of Haematology, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland e-mail: philipmurphy@beaumont.ie
Hi.. have you had a red cell mass test?… that’s usually another way to confirm what’s going on with the red blood cells… I was diagnosed with ET 5 years ago. Platelets ranging from 650 to 900.. had a bone marrow biopsy which confirmed ET, but then after 4 years the haematologist at Guys noticed borderline high HCT 45-46… which is still in range for a male, but higher than the range for people with MPN, who should stay under 45..
the red cell mass test concluded a higher proportion of red cells in the HCT which is made up of red cells and plasma.. so was re-diagnosed as PV..
Long story short, even Guys in London are still not clear if I am ET which has progressed to PV.. or still ET with mild PV like characteristics..
My allele burden is low (15%), with PV it usually is much higher.. and they haven’t felt the need to run another BMB to try and reclassify as not concerned…
I guess what I’m trying to say is sometimes it’s not as clear cut as progressed from one to the other… sometimes it is… if you haven’t had a BMB, that’s the best way to get a sense of what’s going on at the molecular level.. perhaps alongside a Jak2 allele burden and red cell mass test. Get all the data you can and compare to your original baseline… or use this to establish your new baseline to track against going forward
From my personal perspective nothing changes apart from now having to have venesection quarterly to bring HCT down.. I’ll focus on what’s in my control, diet, exercise, state of mind, which I honestly believe has been key to remaining largely asymptomatic
I’ve also discussed interferons to get the dialogue going which Guys are supportive of and I will consider at some point - whilst there’s some debate in this forum and across the wider mpn experts as to whether interferon reduces the risk of progression and the potential benefit of starting in low risk young mpn patients… One thing is clear.. aspirin and venesections alone has ZERO chance of halting progression.. so at some point when the time is right for me I’ll be starting.. or pushing for whatever the best therapy is if something newer comes along!
No, I have not heard about red cell mast test. I did give a sputum sample to a medical student working with my MPN specialist in May but when I contacted them about my increased blood work I also asked about the results and was told that the sample has not been tested yet because there are other priorities. So, therefore I do not know my allele burden at the present. I believe it was 10% at diagnosis 5-1/2 years ago. My blood work was positive for JAK2+ at time of diagnosis so the Hematologist at the time did not find it necessary to do a BMB. So, never had one done. Perhaps, I should request with the results of the new labs. We will know more in 1 month when I go for blood work.
It's Red Cell MASS test, not mast, but in any event, most doctors don't order it any more because there are better and more definitive tests that can provide more useful information.
Have you had a bone marrow biopsy? Be cause that is almost always useful, and is the most definitive test because it shows exactly what is going on in the bone marrow where the stem cells live, Also it can help figure out what if any, other genetic mutations you may harbor, which has been shown to affect treatment outcomes beyond even alelle burden numbers.
As others have noted, ET to PV is well known. I see in your prior post your PLT was 1000 and the HU worked well then. But clearly it's no longer working as well.
It's understandable that your Dr is concerned with HCT level, for female ~42 max is the goal for MPNs. Could be without HU your current level would be even higher.
Table 1 here gives the WHO criteria for a PV Dx. You're below the HCT/Hb limit but your HU therapy is likely a factor.
The red cell mass test Steve_Essex notes is in Table 1 and has been considered definitive, but has fallen out of favor partly because it's a" cumbersome and costly test" My Dr also said it's good but the chemicals that are needed are difficult to get these days.
A BMB and full genetic testing are worth asking for. You can know your Jak2 allele % and also get NGS( nexgen sequence) that will check any other mutations. Table 1 of the WHO list tells what the BMB means.
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EPO is a minor criteria for PV in the WHO list. It may be "minor" because low EPO is also seen in ET, as discussed for one study in this post:
"EPO levels were low in 62 of 177 confirmed ET patients"
I think I may be on this group.
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My thought to your question is you may have progressed -and- (not or) you're no longer responding as well to HU. Adding more of it could help for a time but as Hunter notes there are other modern options for PV.
In the US a PV Dx has some advantage over ET Dx since you get on-label access to both of Besremi and Rux. I switched from HU to Bes even though the HU was working fine. My mutation decreased and all was great. But with very rare and a severe adverse reaction to the IFN I'm now on Rux.
Both IFN and Rux can reduce your mutation which is increasingly (last few years) seen as useful.
In sum my opinion, with your new PV Dx, is you should discuss these on-label options beyond HU.
For me my BMB, Jak2 level and declining HCT,Hb tests at Dx (I've posted on that) point to ET, but I'm happy with the PV Dx for its access to more on-label treatments. You should be sure to have a series of HCT/Hb readings near your PV Dx to check for trends.
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Please have that conversation separately apart from my question. 
PV progression
Doctor thinks I have PV
now my local Heme/onc says I have ET not PV and it matters how they treat me. 
Knee replacement fears while having PV
