PV and CML?

[DougyW]

hi just diagnosed with PV JAK2+ve. I also have 1 type of my white cells slightly high. Could I have CML at the same time as PV. My hospital notes had CML?

[hunter5582]

I am thinking that if the hospital thought you had Chronic Myelogenous Leukemia they would have been quite clear about that. Sometimes you will see notes like R/O CML, which would mean to rule this diagnosis out. Please be sure.to verify the diagnosis with your MPN Specialist.

Note that leukocytosis can be a componant of PV. This is fairly common with PV.

Do please follow up and let us know what you learn.

[DougyW in reply to hunter5582]

Thanks Hunter. Spoke to my Nurse Specialist yesterday and she said that you cannot rule out having both it would be really rare. What they are trying to do is rulenout CMML. My Bone Marrow results and further blood tests are being reviewed tomorrow.

[Solyesh]

Hunter, as usual, is spot on. Additional potential diagnoses sometimes can be listed to rule out and have a history that that particular track had been researched. In my case when I first went in for my ET diagnosis my MPN specialist was fairly certain that I had ET but had two different pathologists read the bone marrow biopsy to rule out pre-MF or MF. That worried me but he explained that he wanted an accurate baseline - he had reviewed the results and was sure it was ET but wanted a confirmation and also wanted to have MF ruled out for any future considerations (on the report both ET and Myelofibrosis are listed with a diagnosis of ET)..

Best to check with your MPN specialist as no question is too small and def not worth additional stress!

[EPguy in reply to Solyesh]

Did you know what in your BMB caused Dr to inquire so carefully?

[Solyesh in reply to EPguy]

I did ask that question. While he was almost 100% that I had ET given the blood work (consistently high platelets with leukocytosis and all my other RBCs (Hematocrit and Hemoglobin) WNL) - he did not assume it was ET without the BMB analysis, In fact he wrote on the initial order for the BMB - "MPN: ET? Myelofibrosis?"

It is his standard of care to strongly recommend a BMB for all patients at initial time of diagnosis. Given the initial relatively high Jak2 allele burden for ET (done first by peripheral blood and then confirmed on the BMB sample) of 40% and the persistent leukocytosis, he wanted to check to see if we were dealing with ET or pre-MF/PMF (he had mentioned a study that indicated allele burdens of >50% in ET could actually favor a diagnosis of prefibrotic PMF rather than ET). While I had not been diagnosed for years, we do know that both my platelets and WBCs were elevated for at least 6 years prior to diagnosis (likely meaning I had already been living with ET for anywhere from 6-10 years prior to official diagnosis). Given absence of fibrosis in the BMB (beyond what is normal) it was confirmed to be ET.

[EPguy in reply to Solyesh]

I agree on BMB at Dx, I'm glad my Dr ordered it. Not all Drs agree.

Lots of info. So the relatively high AB of 40% for ET was a key factor. > 50% would be high for ET. I had 14% blood, 19% BMB, not identical.

What was your WBC at Dx? I had just at -/+ the upper limit with one outlier reading.

So your fibrosis was grade 0. I had 0-1. Both are known in ET. I also had high PLT for years before Dx.

[Solyesh in reply to EPguy]

Yes - also very happy my MPN specialist heavily suggested the BMB. According to my doctor the average (across various studies) allele burden for ET is about 25% in BM so the 40% was relatively high (as was cellularity). My WBC readings prior to beginning cytoreduction (first HU and then Peg) were: 13.1/14/6/14.3/12.6 (over 8 months) so consistently high WBC/leukocytosis (our labs use a reference range of 4.5- 11 10*3/micl)

[PhysAssist in reply to Solyesh]

For what it's worth, I may be kind of a rarity, because from the beginning, I clearly met all the diagnostics for PV:

I was Jak2 v617f-positive on peripheral blood with trilinear cell line hyper-production on BMB, with an JAK2 Allele Burden [AB] of 39%, which is on the low end for PV, but pretty close to yours, and a low-normal erythropoietin level.

...and that's after well over 10 years of both symptoms and elevated H&H.

Your [^'er than usual for ET] AB may be the reason why your WBC's were elevated.

It seems like not too many of our disease processes "want to be" purely one flavor or another- many seem to have some cross-over with other MPN diagnoses.

[Solyesh in reply to PhysAssist]

Yes, my doctor always reminds his patients that the MPNs should really be considered to be on a continuum and that any one primary disease can have characteristics of the others - this is why at times it can be difficult to diagnosis exactly what we are dealing with (especially between ET and pre-fibrotic MF) - this is also why he counsels his patients to get a BMB at diagnosis to allow for later comparison, if need be.

In my case the BMB did clearly define the hyper-production of the megakaryocyte line (and none other) and no fibrosis defining it as ET but with a high (for ET) allele burden and also a low EPO level....

[EPguy in reply to PhysAssist]

trilinear cell line hyper-production is a classic PV result from my recent learning. But the continuum does continuously come up for good reason.

[EPguy in reply to Solyesh]

Sorry if question is redundant, but do you have a % cellularity? I recently posted on this as I learn about it.

[Solyesh in reply to EPguy]

Great question - yes % cellularity was listed in my report and it was another key reason my MPN specialist wanted to have additional eyes on the report. The initial report stated Cellularity of up to 80% - which for my age and ET is "super" hyper cellular (the expected range for me would be 40-60%). So in theory with the higher than average AB and significantly higher Cellularity plus the persistent leukocytosis and the low EPO - I pushed the doctor as well for a differential diagnosis - were we dealing with ET or PMF.

At its core it is an interesting research question but unfortunately today not of much clinical use - initially my treatment would not differ as PMF is truly only clinically significant if it progresses to MF - if I stayed at the PMF stage for the rest of my life it would not have changed how we treat the disease vs if I stayed at ET...treatment would be driven by QOL issues and symptom burden, etc.

Having said that...all the research I had done was giving me significant stress that the characteristics of my particular MPN even if starting out as ET did not have the best prognosis and progression was more likely in my case than in an average ET patient. My MPN specialist was very patient and reviewed the reams of research I presented him with (and even asked why I had not reviewed his latest paper on the subject - he was understanding about the potential stress/worry the information might cause but from a clinical/medical standpoint the science is not there (yet) as to determine, despite the characteristics, who is likely to progress and under what time frame.

He was willing to push the envelope however and ordered both cytogenetic analysis and an NGS panel. Outside of CML, cytogenetic analysis is not super helpful as specific chromosomal abnormalities have not been identified for MPNs other than CML, and abnormalities range from <5-30% and are varied (this is an area of the science of MPNs that needs attention) - good news came back from both tests as no abnormalities beyond Jak2 and minimal TET2 (he said fell under the significance threshold for the lab but knew I would want to know) - chromosomes appeared normal and importantly no abnormalities along any of the chromosomes or combo that might predict transformation to AML.

After all this and to make along story long - the official diagnosis remained ET - but the knowledge did push me to research more about interferons and to push for Peg as soon as practical.

My doctor had pointed me to some good and fairly straight-forward studies on differential diagnosis at the time of my Dx - one of my favorites was out of Canada and can be found here:

academic.oup.com/ajcp/artic...

and another good differentiation and prognosis study here:

arupconsult.com/content/mye...

I hesitate to post studies in general only because unless you have knowledgeable medical advice to help understand them they can lead to additional stress. I do go through them, note questions/concerns and then can discuss with my MPN specialist...I am a big believer that no question is insignificant and having unanswered questions aren't worth the stress...

[EPguy in reply to Solyesh]

One member has posted a cellularity of 100%, so we have an example of an upper limit. If it's ok, what is your age? 80% does seem in the hyper category.

My BMB said hypercellular, I recently asked Dr my %, at 40-50 it doesn't seem so hyper for a 61 year old. The subject seems quite loose in definitions.

Those reports are deep, lots of info.

I had an abnormal karyotype of no known hematological significance.

[Solyesh in reply to EPguy]

From what I've read I would agree that 40-50% is not "hyper" for someone 61! I was 50 when I had the BMB done so we would have expected somewhere in the range of 40-60%...