MPN-U or MPN Unclassifiable

[Jimbosan]

Initial Dx was PV but failed to meet all criteria. I began seeing an MPN specialist and had Next Generation Sequencing done, and he reclassified me as MPN-U. I have mild fibrosis with low symptom burden, but in addition to Jak2, I have three other Tier 1 mutations. Only take 500mg of Hydroxy four times a week now. Lately, blood counts are dropping, and I may eventually be tapering back on Hydrox and switching to MF-type drugs. Are there any other MPN-U folks in this group? I would love to get specific with someone with experience with this type. Doc said it would eventually manifest as either ET or MF, with the latter being the most likely outcome. At 67, the 10-year survival for either he gave me was not terrible. That an average, and I always feel above average, as everyone does.

[Paul123456]

I’m MPN-U PV which I assume means I’m somewhere between PV and MF, more PV than MF.

I’m JAK2 and TET2 and on Pegasys which is a great drug. If I was able to reverse time I’d have started Pegasys upon dx. It’s the only current drug that might be disease modifying, as in a near cure for some lucky people.

What other mutations do you have. I’m afraid multiple mutations increases the risk of more mutations, some of which are best avoided if possible. Hence I’d advise regular myeloid panel tests to keep track, especially if you might consider SCT at some point in the future.

The good news is that there’s lots of new treatment options in the pipeline, especially combination therapies. Next few years could be transformational

Best Paul

[Jimbosan in reply to Paul123456]

Very impressed with these responses. I'm not on FB anymore! Attached more details of my NGS and BMB. Thank you all for your responses. Great resource. I'm at UCSF and like my Doctors approach, but monarch5000, you are right about the age barrier there.

comments from pathologists

[Jimbosan in reply to Jimbosan]

Tried to load this in my original reply to paul123456

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[monarch5000]

Agree with Paul123456. If you want to maintain your "mild fibrosis with low symptom burden" and reduce your Jak2 allele burden I would also suggest Pegasys or Besremi interferon. Hydroxy is just a blood clot risk reducing drug. Jakafi is too and is also a enlarged spleen reducing drug. But only interferon offers you the chance of avoiding progression to advanced MF. Avoiding progression is important for a 67 year old because by the time you are 72-75 you could classified as too old to qualify for stem cell transplant. In the USA most hematologists won't offer interferon to 60+ year olds so sometimes Senior aged patients have to travel afar to known interferon friendly and experienced hematologists to try and obtain a prescription.

[Wyebird]

I do hope it doesn’t change to MF. If at all possible Do consider Peg.

[violetta115]

Hi Jimbosan, I am also DX as MPN-U, originally diagnosed as ET by a local hematologist because my platelets were 915, and I immediately was started on Hydroxyurea 500 mg daily with 1 baby aspirin. My other tests showed hematocrit at 49.5, RBC 5.57, and WBC 7.38 and hemoglobin 16. My BMB report stated that I met the criteria for PV. I had Jak2 21% and Tet2 42% . However found in my bone marrow aspirate, was increased iron stores ,which is atypical for PV. I also had no significant bone marrow fibrosis. After 1 month on Hydroxyurea my platelets were at 298 and have been in the normal range since then as have my RBC, WBC , HCT, HGB, I am now under the care of an MPN specialist at Weill Cornell and am diagnosed as MPN-U close to PV but not a perfect fit. My main symptom is fatigue at times. I am considering the switch to Besremi as my doctor is recommending for the reasons stated by Paul and Monarch . Not an easy decision for me.

[EPguy]

Did your Dr say which criteria you failed to meet for PV? Was your HCT too low? Maybe it's that you also have criteria for more than one MPN type.

This reference has criteria your Dr may have been considering. Unique to PV is:

" hypercellularity for age with trilineage growth (panmyelosis)"

which you have in your BMB.

But the "atypica" fits your "atypical" result and this relates to Pre or MF, which may explain your Dr's likely prognosis.

These two different features may explain the MPN-U.

The "less than 5% blasts" and "rare blasts" is looking for leukemia precursors as I understand it, and that result is good as normal blood is in that range.

ncbi.nlm.nih.gov/pmc/articl...

[Jimbosan]

Thank you, EPguy. My Hct has never reached >49%. Hb never stepped out of bounds, either. The most significant platelet count I've had was 890. I'm on the slow burner but retired with time on my hands, so I review literature periodically as well, and I appreciate the quality of the literature you sent. I can't claim to have the capacity to comprehend MPN literature as well as a physician, but I have seen enough to know that many physicians don't either, and I have never had one admit to not really knowing about MPN when I mention it, so you can't count on your dermatologist or surgeon having a comprehensive understanding of MPN. This disease has given me a new hobby. I dropped out of high school in 1972, prior to any exposure to biology. Now I am learning about human biology, blood cells, and genetic material- it is blowing my mind. Thanks again.

[EPguy in reply to Jimbosan]

Those aren't so extreme numbers and do seem consistent with the ambiguity. I also had many HCT readings 46-48 near Dx but one outlier was 50.8 which I think triggered the PV Dx. My PLT maxed over 1000 and were consistently high so with Jak2 some MPN was clearly in store.

I agree most GPs know less than well informed forum members here. But the various Drs I deal with haven't claimed to know much which in light of your experience I appreciate. But the right specialist is the proper guide.

Same as you I'm motivated to really understand our condition.

[ERei]

I am also now considered to be MPN-U. I was initially diagnosed by my local hematologist as PV after having a high Hct & Hgb and having further studies which revealed that I am Jak2+. I eventually went to an MPN doc who said to officially meet the WHO criteria for PV, I need to have a BMB which should have been done when first diagnosed. The BMB interpretation was MPN-U. The MPN doc said I am probably PV or possibly ET which will be transparent in the future.

[EPguy in reply to ERei]

Depending how high your HCT etc was the WHO 2016 can provide PV Dx without a BMB. But likely yours was not that high if the expert did not Dx PV from it. I agree a BMB at Dx is worth having for future reference in any case.