« JAK2 V617F allele burdens were positively correlated with white blood cell counts, hemoglobin values, lactate dehydrogenase levels, and platelet counts. The median values of JAK2 V617F allele burden in patients with PV and ET were 58% and 30%, respectively. A JAK2 V617F allele burden of ≥30%, older age, and a higher hemoglobin level were risk factors for thrombotic events in ET. In patients with PV, older age was the only thrombotic risk factor. The 8-year probabilities of overall survival (OS) were 82.9% in all patients. A high JAK2 V617F allele burden (≥58%) was associated with poor OS in patients with PV. For the patients with ET, the difference in 8-year OS based on the JAK2 V617F allele burden was not significant ».
Conclusion
The JAK2 V617F allele burden was correlated with hematologic parameters and clinical outcomes. Assessing the JAK2 V617F allele burden can be helpful in predicting the thrombotic risk and disease course in patients with JAK2 V617F-positive PV and ET.
When you turn 90 please post again and let us know how you are doing. We can't worry about statistics, just live your life. What treatment are you taking? I am 72 and PV. Live long and prosper, best to you always.
Sounds like you have done very well with your treatment. Do you still require venisections? How often do you have blood tests? Thanks, I am wondering how often I should go in for CBC's now that covid is rampant in our community. Best.
Had a venisection yesterday the previous one 3 months ago and before that 10 weeks in a row in May onwards 2016 when first diagnosed.I currently attend the clinic every 6 weeks but have only seen the heamotolgist once in the last 3 years.My bloods have been fine up to January 2021 when I was diagnosed with Polymyalgia and put on Predisllone which has caused trouble with my bloods
Small study sample, but I'm surprised that ET seems to be more of a thrombotic risk than PV.
I have ‘ET’ (possibility of masked PV), I don’t know my allele burden (if above 30%) along with my age and high haemoglobin would seem to put me in the thrombotic risk group ‘if’ I have true ET? Have I interpreted that right?
<<JAK2V617F variant allele frequency >50% identifies patients with polycythemia vera at high risk for venous thrombosis>>
Some comments, and I welcome any critiques on them:
The plots here from the study clearly show the relation to allele. For PV, upper left, Survival (OS) is indeed affected by allele, and thrombosis (TFS upper right) goes way down to 50% by 8 years. As charl17 says here, is it useful to get allele down? I share that question. Absent a solid answer my bet is assume it is so and consider asking your Dr about INF to get under this value. (or 50% allele per the study "allele frequency >50%" above. ET has a better OS as has been found before. The TFS numbers are unexpectedly low, but see discussion below.
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Some questions:
As in some other studies we've seen, for PV, the "elephant in the room" is avg HCT of 56. (Table 2) Seems they are following patients that are not getting current treatment standards. In their discussion <<Many factors, including ..., and treatment factors, may influence the long-term outcomes of PV>> It is well known that HCT above 50 is a large risk factor. Most PV patients on the Voice I believe are controlling HCT and would like to see studies that follow such patients receiving this "treatment factor". My guess is it would help those low TFS numbers.
Regarding their correlation of HB to allele, Tables 2 and 3 show identical Hb for the respective allele ranges of PV, ET. (both allele levels of PV have Hb= 18, and ET = 13) I may be missing something but if not this is a signif discrepancy from their claim.
The study found a higher frequency of thrombosis compared to a prior study. Authors note that <<The difference might be due to a selection bias stemming from the small number of patients (n = 127)>> In the prior study n= 1,235 and it showed << Patients with JAK2-mutated essential thrombocythemia and those with polycythemia vera had a similar risk of thrombosis>>
In the prior study (Table 2) LDH was about 1/2 that in the present study. See plot in my next reply below of my LDH. I assume my decrease is from the HU therapy that spans most of this period. So the present study seems to have untreated LDH (if it is in fact broadly treatable) This may account for some of the higher thrombotic events or other negative effects of high LDH. In:
<<LDH might supersede leukocyte count as an independent risk factor for overall survival in ET>>
In sum, it would be good if some future studies followed patients receiving current standards of care so that those with controlled blood numbers can then compare alleles under best case conditions.
Thanks for your scrutiny and evaluation, very useful.
My wbc were low at ET diagnosis (6) and are roughly in the 5 range on treatment, so something good, although I don’t know my allele percentage or LDH levels. Impressed your LDH counts have fallen significantly whilst on hydrea, that has to be good.
Thanks for the scrutiny. It takes time to look into the studies but the brain exercise is useful in various ways. It seems not unusual to find inconsistencies in some studies, but it has been a surprise to me as they are supposed to be "peer reviewed". More broadly how much interpretation is left to the reader has been unexpected. Before my MPN Dx I never looked into these things.
Your scrutiny is very much appreciated and so glad to hear you seem to get pleasure from it.
It’s the TFS I was interested in, as for ET, it mentions high hgb levels and age as being a poor predictor. As you say, it would be extremely useful to mention if patients’ were treated/untreated. I find it hard to interpret. For example, ET - hgb levels 13 - does not seem high to me (appreciate that’s an average), but is that treated/untreated? My own were 16 at diagnosis, and around the high 14 now. Am I missing something?
I must admit when looking at studies I tend to jump to ‘discussion and conclusion.’
Not entirely pleasure, more like my daily exercise, it's good for the health. Also I like to help the others here. Agree on viewing the dessert 1st, it's like watching the movie vs reading the book. Problem with the in depth as mentioned is it leads to more questions, which is how science works anyway.
The studies here that included ET had similar, and wide hgb ranges. I'm as yours, hgb started high but has never gone that low either, see plot. (low point is after high dose start for HU) HCT stays under 44.
According to the top post study here for ET : <<higher hemoglobin (OR, 1.26; 95% CI, 1.09–1.54), and V617F allele burden ≥30% (OR, 1.03; 95% CI, 1.00–1.08) were identified as risk factors for thrombosis>> with Table 4 showing a very high odds ratio of 1.26. For PV high Hgb much reduced thrombosis risk at odds of 0.87.
Another stand-out in table 4 is extreme risk ratios of being female, good risk for PV, (0.58) bad for ET (1.58). So sex, and HGB are stand outs for risk in this study. But in the "JAK2V617F variant allele frequency >50%" study above, Table 3, the gender PV risk is the opposite with male being favored at 0.7.
So gender has opposing effects in two studies. It's hard to keep track of it all and I don't do spreadsheets unfortunately.
I would think with the retrospective data these authors have they could select a subset with tight and well controlled range of blood numbers and look at just allele.
If I were to take the findings of this study seriously, the following would seem to apply.
If I have true ET my TFS is poor (high hgb/female) however, in my case there is a possibility I may have had ‘masked PV’ at diagnosis which would seem to have the opposite effect ?
What I find hard to understand is, ET presents with raised platelets whereas, PV in many cases presents with all blood counts raised including platelets. I would have thought for PV that alone would elevate the risk of TFS over ET.
The thing is it is a small study sample with some discrepancies highlighted by yourself. So, for me at least I won’t take the findings too seriously.
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Eye floaters
PV at 28
ET jak2 to PV
