by David Wallace
Dr. Ghaith Abu-Zeinah, Assistant Professor at Weill Cornell Medical College, Silver MPN Center is our MPN specialist answering this important question.
David Wallace, PV Reporter, is your host and patient advocate.
TRANSCRIPT | Has PV become a disease of the middle-aged?
For many years PV been considered an older person’s disease. And, and we typically hear that you know, the average patient is in their sixties and from my observational analysis out there, I’m seeing a heck of a lot of patients that are being diagnosed in their twenties, thirties, forties. And I’ve got to believe that shifting the average age, perhaps in the fifties I wonder if you can give us an update shed some light on that.
Absolutely correct. For the longest time has been thought of as the disease of the older patient and the median age has been reported in several studies in the literature. And even if you look at our national registry in the US in the early sixties, 60 to 65, our data suggests that the median age of diagnosis is around 54. So it’s actually earlier now there’s different ways that this could be possible. One of them is that, the disease could be detected earlier. You know, if you’re at an institution or a place where you are more vigorous with screening testing and patients, you know, go to see their physicians more regularly PV could be detected earlier. It could be diagnosed per the WHO criteria, with the JAK2 testing and the bone marrow biopsy that could be done earlier.
And it could be found earlier in the disease course. So that is one explanation. The other explanation is it is possible that the dynamics of this disease, the epidemiology of it are changing in, in this day and age that younger patients are getting PV for one reason or another. Now we don’t know of any particular environmental factors that associate with PV, but I do agree with the observation that certainly it seems that younger patients are getting PV. It’s a question of whether it’s just being detected earlier or there’s a reason for that. I will say that there was a very important Danish study that shed some light on sort of the precursor to PV and MPN called chip CHIP, which is clonal hematopoiesis of indeterminate potential. That means that there is a mutation that’s present, that’s causing clonal hematopoiesis or blood cell production at a clonal level that has indetermined and potential or unknown clinical significance.
That used to be the case until more recently, we now recognize that having chip is also associated with some of the same risks that we see with PV, but to a much lesser, lower degree. So the Danish study that I was referring to as a population study that looked at the presence of these mutations, including JAK2 and CALR in roughly around 20,000 individuals in the population. So these are presumably healthy. Some of them had some illnesses but they were tested and, and it was found that approximately 3% them had a JAK2 mutation. So that is actually a very high number, because if you put that in perspective three in a hundred, having a JAK2 mutation, when PV as a disease is more like on the order of one to 10,000 there clearly is something there there’s a story to tell.
So the prevalence of these mutations now is more than we’ve anticipated. And part of it is owing to the improvement in technology, in detecting these mutations at very low level. So chip patients can have these mutations at a allele frequency of 1% or 2%. So really only one or 2% of their blood cells are JAK2 mutated, but now we’re detecting those patients. So with the knowledge that there is a JAK2 mutation when patients develop blood count abnormalities, that generally leads to further investigation that establishes the diagnosis of PV. So in, in this same study, the 3% of patients who had the JAK2 mutation I think around two to 3% actually had an MPN. So putting it in the flip side, 97% of those with JAK2 mutations did not have an MPN or did not have a diagnosis of an MPN. So there is, there is a spectrum. I think there’s a spectrum. And to show you how many patients there, there could be. I, I truly think that the age gap or the change in the age of diagnosis is primarily related to the timing of testing. And you know, when patients are coming to medical attention, and I think as, as time goes by, we’re diagnosing it earlier and earlier because we are her at detecting these diseases.
Publisher’s Note by David Wallace
Although this discussion was based on PV, it’s very important to include ET as the same premise holds true.
Based on data from LLS, which shows ET being diagnosed slightly younger than PV and this study showing “there has been a decrease in the age of ET diagnosis, 56 years versus previous data of 60 years” both PV and ET are diseases of the middle-aged.
Recent data suggests polycythemia vera and essential thrombocythemia are No longer an “older folks disease.”