Currently I am being treated for PCV and taking Coumadin (hx of Blood clots x2) and Besremi since June 2022 per my MPN specialist in Denver, CO.
I saw a MPN specialist at the Mayo Clinic last week and he advised me that based on the WHO criteria for PCV that my MPN is unclassified. Although I clotted off my liver (Budd Chiari syndrome) May 2021 and my HCT was 55. He suggested that I switch to Eliquis and a baby Aspirin and stop the Besremi 100 mcg every 2 weeks and start getting phlebotomy to keep Hct less than 45. I do have autoimmune issues so he feels stopping the Besremi would help my alopecia and vitiligo. He also feels that it’s not good to be on a chemo drug indefinitely. Receiving two different opinions is very confusing. Can anyone tell me about their experience with Phlebotomy only. Kinda scared to just do that and stop Besremi. Any advice is appreciated as this is causing a lot of anxiety.
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JeanieRN
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My situation appears to be different than yours. I am confirmed to have PV and do not have an autoimmune disease. I am hydroxyurea-intolerant and it was not effective for me. I did use a phlebotomy-only protocol for about 2 years. As you are aware, therapeutic phlebotomies induce chronic iron deficiency. This is the intent. your body cannot make RBCs without the iron needed to make them. Unfortunately, iron deficiency without anemia, to goal of the phlebotomies, can also have adverse effects. For me, these included, loss of energy, decreased ability to concentrate, alopecia, and reactive thrombocytosis (+200K).
Ultimately, the iron deficiency symptoms were worse than the PV symptoms. That is why I elected to opt for the interferons. While I have had some minor side effects from the Besremi (itching/rash, mild leukopenia) it has been very effective and I have had a Complete Hematologic Response. The actual adverse effects I have experienced are not as bad as the iron deficiency effects.
Note that this is my experience based on my MPN Profile. Your situation is different. Your experience may well be different. Given your profile and gender, I would think the HCT target should actually be 42/43%. It is very important to achieve the target for controlling erythrocytosis. This is your greatest risk factor. It is also important to control for the other MPN symptoms, including inflammation.
Given the complexity of your case, it is not surprising that you have heard more than one opinion. The answer is not black-and-white. Suggest you think through your treatment goals, risk tolerance, and preferences. Perhaps find a knowledgeable friend or an uninvolved medical professional to help you sort through the pros and cons of each option.
Hope you are able to sort through this morass soon. All the best as you move forward.
Thank you very much Hunter for taking the time to reply. It helps to hear your experience as one of the things so am trying to combat is the alopecia and not make it worse but having an even lower iron level as I have now. Now that you have complete hematologic response are you able to lower your frequency or dosage of Besremi?
Not yet. I am at 150mcg every two weeks and stable. The issue is that as my iron levels recover, the erythrocytosis will also increase. I feel much better on Besremi with my iron levels higher, but they are still not normal. It is all a balancing act. Get my iron levels higher without inducing HCT>45% while at the same time keeping the adverse effects from Besremi tolerable. I might be able to tolerate a slightly higher dose of Besremi but it is not certain. Only time will tell.
"Criterion number 2 (BM biopsy) may not be required in cases with sustained absolute erythrocytosis: ... in women (hematocrit, 49.5%) if major criterion 3 (Jak2) and the minor criterion (low EPO) are present"
Do you know your EPO level and Jak2 status at the time you were HCT 55? You've not had a BMB correct?
Re Chemo: IFN is not technically a chemo, it's a biologic (medications that come from living sources). HU is chemo. And IFN is in most cases used for very long periods ("indefinitely") by most MPN patients, so the generic concern there is strange. PHLB also has risks over long term as noted by Hunter. Has Dr discussed that trade off?
Hi, yes my Hct is currently 43. I s as m currently on Besremi 100 mcg. I did need to have a phlebotomy last month for my HCT 45. Yes, my vitiligo and alopecia seem to be worse. Although both disorders did start progressing last Dec. three months prior to starting the interferon. To hard to know 100% if Besremi is the sol cause. My hypothyroidism has been stable. I am not sure what my erythropoietin was.. i wasn’t tested for Jak 2 mutation until 2 months after my clot (Budd Chairi) that put me in the hospital with multiple complications for 7 weeks. I did have a bone marrow biopsy. I am Jak 2 positive with an alle burden of 12. Thank you for clarifying what type of medication intereferon is. Not sure why my MPN doctor at the Mayo called it a chemo drug. That was alarming to me.
I can’t tell you all how much your feedback is helping me to try and figure things out! Thank you!!
My opinion is your Denver doc is more informed and that the Mayo doc has archaic, old school views and approaches to treatment. If I were in your situation of high HCT (55) I would try to bring it down to around 45 combining Jakafi with Besremi interferon or Pegasys interferon. That way you'd likely need alot less phlebotomies, hence would not suffer the substantial consequences of iron deficiency.
The Silver MPN Center in New York City published this data on the long term outcome of phlebotomy-only treatment:
20 years after diagnosis: (PV stands for Polycythemia Vera)
85% of PV patients who had been treated with interferon had not progressed to MF
59% of PV patients who had been treated with hydroxyurea had not progressed to MF
51% of PV patients who had been treated with phlebotomy-only had not progressed to MF
95% of PV patients who had been treated with interferon were still alive
63% of PV patients who had been treated with hydroxurea were still alive
57% of PV patients who had been treated with phlebotomy-only were still alive
Your BMB does show some ambiguity. I've tried to learn about this because of my also ambiguous Dx, here are a lot of details if you're interested. This is only my non-expert opinion:
Your BMB shows "trilineage hematopoiesis" This is a good thing, being a normal process "normal production by your bone marrow of three blood cell lines: red blood cells, certain white blood cells, and platelets." healthline.com/health/hemat...
In the WHO PV Dx, there is excess of these three types, which is not your case: "polycythemia vera is a panmyelosis because of elevations of all 3 peripheral blood components." These are the cells that make Red, White, and PLT. msdmanuals.com/professional...
In WHO ET has "enlarged, mature megakaryocytes" You have the large Megas. But "atypical" megas is not in the ET section.
On your cellularity this is a plot from one report I've posted. So at age 52, 50-70% is high and matches PV on WHO "...hypercellularity for age".
So while your 55 HCT, and Jak2 point to PV, the absence of EPO result means this shortcut to PV Dx in WHO list does not apply. Hence the BMB provides more (but ambiguous) info.
My BMB looks ET like, but I have PV Dx.
Your note on the immune trouble suggest that starting the Bes is not when it got worse. But doesn't mean the Bes is not aggravating it. If I had to make this choice, I'd try to stay on Bes unless the autoimmune issues become a clear risk. Could you ask Dr about reducing dose to supplement the PHLB? Are your liver numbers (ALT/AST) ok? These are among those relevant when taking IFN.
Negative FISH is a good thing, I believe this means no chromosomal abnormalities, as is no fibrosis (the F in MF). Blasts are immature white cells and are present in leukemia, so they usually look for it, and found none in your BMB.
That does not really make sense. Besremi can keep HCT <45% without phlebotomy, achieving the same treatment goal without the adverse effects of chronic iron deficiency. It is true that Besremi can have its own adverse effects of course. Which set of AEs are worse depends on the individual.
How did the doc interpret the BMB findings from 2/15/22? Is there any update?
He just insisted that I didn’t have PVC, because the WHO says your Hct need to be greater than 45 for a prolonged That in itself was confusing because I wouldn’t want to risk it to have it over 45 considering my clotting hx. He said The true effects of Besremi are still unknown because it hasn’t been around long enough. Honestly I am so confused. I have been back to all my normal activities like running, biking and swimming . I hate to start feeling totally rundown due to low iron levels from phlebotomy. Luckily I have a visit with my MPN specialist next week to discuss all of this. Although, I must add my Mayo specialist is World renowned and has published 1000 articles. The other thing he did say was if I chose to go off the Besremi for 6 month (to see if my autoimmune issues improve) we could then look at Jakafi which is now FDA approved for vitiligo and alopecia. But Jacafi has it own set of risk. So hard to know! My biggest concern is that I have 3 teenage daughters and a husband. So even if I loose all my hair and my vitiligo spreads I want to do the treatment that is going to give me the most time to live and enjoy life with my family. I am only 52.
The HCT would have to be greater than 48% for a woman, or alternatively HGB greater than 16.0 g/dL to be diagnostic for PV. Not sure what HCT. HGB you were running prior to treatment.
Your BMB result does list hypercellularity. Note: For a 53 year old, the normal range for cellularity would be 38%-58%. labce.com/spg28528_evaluati...
Diagnostic criteria for PV as per the 2016 revised World Health Organization (WHO) guidelines include three major criteria and a minor criterion. Diagnosis requires the presence of either all three major criteria or the first two major criteria and the minor criterion
Major WHO criteria are as follows:
Hemoglobin >16.5 g/dL in men and >16 g/dL in women, or hematocrit >49% in men and >48% in women, or red cell mass >25% above mean normal predicted value
Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size)
Presence of JAK2V617F or JAK2 exon 12 mutation
The minor WHO criterion is as follows:
Serum erythropoietin level below the reference range for normal
That was a lot of words that actually do not really address your core issue. There could be debate about PV vs MPN Unclassified. Different doctors may interpret your case differently. Doctors do not always agree. You now your own history. What do you think?
The bottom line is what your treatment goals are and what your risk tolerance is. If you have a history of thrombosis, it makes very good sense to keep your HCT<42/43% for a female, regardless of whether it is PV or MPN unclassified. The question is how best to do this. Besremi, Jakafi, and therapeutic phlebotomy are all viable treatment options. Each has pros and cons.
There is evidence that Besremi may provide better progression-free survival. It is too new to know for sure whether this will prove true in clinical use. There is also evidence that it can reduce allele burden. While many feel this is significant, not all agree. Besremi does do a very good job of controlling erythrocytosis (and thrombocytosis/leukocytosis) for some of us, however, not everyone can tolerate it. The autoimmune issues are a significant concern.
Jakafi also has clear benefits in terms of symptom control. Given some of the issues you describe, it is a reasonable thing to consider. There are potential side effects as there are with all of out choices to treat MPNs.
Therapeutic phlebotomy can certainly control erythrocytosis. I used it successfully for a couple for years before the side effects became worse than the PV symptoms. Do be aware that it can significantly increase platelet levels, which may be an issue if you already have thrombocytosis.
Sometimes we do have to use trial and error to find what is going to work best. Sometimes it is actually a combination approach that works best (e.g. lower dose of medication combined with more occasional phlebotomy). It would be great if we had more clear answers, but we simply do not always have them. Sometimes we just have to use the best judgement we can and move forward.
I am certain that you can find a viable plan. Have confidence that you can successfully try a number of options until you find the right plan for yourself.
You’re absolutely right Hunter! I need to take a deep breath and realize I can try different treatment modalities after weighing the pros and the cons and if one doesn’t work I can try another. Just really nervous as this all came out of nowhere. Training for a triathlon last year on a Wed then in complete liver failure on a Sunday. I worry most about my blood getting too thick (sludgy) and despite my anticoagulation, forming another clot. I do feel that my high Hct of 55 most definitely contributed to my liver clotting off. Especially since my INR (level to measure your clotting time) was in a therapeutic range. My Hct never did go that high again. It hung out around 41-42 (without any treatment) from 8-21 to 2-22. Then up to 44 in March. That is when I started Pegasys followed by Besremi. My erythropoietin level was 7 a year ago. My Hct was 45 in August (i had my first phlebotomy then) This month it is 42.8. Once again thank you for your input! I don’t need to get it all figured out immediately. Any input on my iron levels are welcome!
Interesting that your high HCT, 55, was not prolonged. That WHO shortcut to PV requires "sustained absolute erythrocytosis (very hi HCT in this case)" So for that and the lack of EPO data, it makes sense Dr did not apply this criteria.
Agree with deep breaths. I need them at times too. You are quite correct. You have time and the ability to try some different things to see what will work best.
Here is a bit of info on iron levels.
• Serum iron. This test measures the amount of iron in your blood.
• Serum ferritin. This test measures how much iron is stored in your body. When your iron level is low, your body will pull iron out of “storage” to use.
• Total iron-binding capacity (TIBC). This test tells how much transferrin (a protein) is free to carry iron through your blood. If your TIBC level is high, it means more transferrin is free because you have low iron.
• Unsaturated iron-binding capacity (UIBC). This test measures how much transferrin isn’t attached to iron.
• Transferrin saturation. This test measures the percentage of transferrin that is attached to iron.
Do not see your Ferritin #. I expect it is on the low side. It looks like your serum iron is just a touch low. In the absence of cytoreductive therapy, I would think that you erythrocytosis would be much mor4 pronounced with this much iron still available.
This is my layman's KISS explanation of how people with PV metabolize iron. Our bodies scarf up all available iron to make RBCs. none is left to put into storage. Any iron we take in goes straight to RBCs. It is, of course, more complicated than that.
If you are interested, here are a couple of articles on PV iron metabolism. Note that a certain level of iron deficiency is the norm with PV before phlebotomies.
Still interested? Here is a great video on general iron physiology. It is actually rather interesting and does help to understand what all of the above means.
The link you have for cellularity includes info I have been seeking. "On the biopsy section the specific type of cells present are difficult to determine" So the excess cells can be any of the three precursor types. (Red, White, PLT) In another reference (I think the video from the Australian pathologist) we saw that ET usually has cellularity as excess megakaryocytes, but as your ref shows, this is not known for certain from biopsy.
The number range is also more generous than the plot I showed here, with the +/- 10% range. By this measure for example I had normo cellular at 40-50% at age 61 while my BMB said hyper. And JeaniRN has a good overlap with the normal ranges.
I was diagnosed with PV Jak2 positive 20 years ago and I have been seeing a Mayo MPN specialist out of Rochester MN. since being Dx. This specialist is one of the leading experts on MPN research & studies......in fact he is cited in practically every article that is posted on this forum. I actually flew from Alaska to MN. to see him in person as my hematologist was getting all her treatment guidance on what to do with me from him. I feel I'm in extremely competent hands. Most hematologists will recommend a drug to reduce high platelets, and high WBC's. especially if your over 60.
My Mayo specialist has always treated me as a individual with PV as each one of us is completely different with how PV affects us, risk factors, drug reactions and other health conditions. I have tried PEG for 7 months and found the drug's reactions intolerable on a dose of 22.5 mcg. Liver ALT enzymes shot through the roof and had other unfavorable reactions. It was like poison for me.
With that said, I've always been considered low risk despite being 61, and have no other health conditions. My Mayo specialist has recommended 2 low dose aspirin a day and phlebotomy as needed which is usually every 3-4 months. I've personally have done very well with this treatment plan even despite low iron. Remember we all are DIFFERENT! For example Hunter mentions the iron deficiency had very adverse effect's for him. For me the iron deficiency effects are minimal compared to what I felt on 22.5 PEG. My recent BMB was conclusive in regards for this treatment working for me. No increased fibrosis or signs of progression despite an AB of 93%. I also do not have additional driver mutations.
My hematologist in Alaska said there are two different modes of thinking regarding treatment for MPN'S and the significance of AB; coming primarily from Mayo clinic and MD Anderson. MD Anderson docs believe that most people should be treated with a drug and they promote INF's and lowering AB. Mayo differs a bit on this approach and doesn't believe one size fits all and they do base a lot of their treatment plans on factual evidence. You must listen to your own body and guide your own treatment plan with this knowledge and the information given to you by both medical institutions.
Sorry for being long winded. Hope this helps. Kerry
Hi Kerry, I too went to The Rochester MN clinic. I suspect we saw the same Doctor. Thank you for taking the time to write this response to me. It certainly helps. Although, I was confused by his recommendations, the doctor did seem very sincere and to have my best interest at heart. He said his biggest fear was another clot and that Eliquis and a baby aspirin should prevent that. I was on Coumadin when I clotted off all my hepatic veins. I guess if I do decide to go off the Besremi it will depend on how often I have to do phlebotomies as to whether I go back on the Besremi or try Jakafi. So much to consider.
What do you mean by additional driver mutations? What are your thoughts on the AB? Just trying to learn as much as I can. Thanks! Jeanie
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now my local Heme/onc says I have ET not PV and it matters how they treat me. 
