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What Is My Risk For MPN Progression?

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Published on October 19, 2020

What Risk Factors For MPN Progression Should I Be Aware Of?

Join us as an oncologist and patient advocate discuss the risk factors for MPN progression. They will cover topics including the risk of essential thrombocythemia (ET) or polycythemia vera (PV) progression to myelofibrosis (MF), the risk of primary myelofibrosis progression to acute myeloid leukemia (AML), what gene mutations are most at risk for cancer progression, and all of the crucial questions you should be asking your health providers on your journey. Dr. Olatoyosi Odenike, director of the Leukemia Program at The University of Chicago Medicine, is joined by Andrew Schorr, Patient Power Co-Founder and Patient Advocate for this segment.

See more information on ET, PV & MF from Dr. Odenike and guests here, as well as on our MPN landing page.

This program is sponsored by Sierra Oncology. This organization has no editorial control. It is produced by Patient Power in partnership with the MPN Research Foundation. Patient Power is solely responsible for the program content.

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Transcript | What Is My Risk For MPN Progression?

Andrew Schorr: 

Greetings from Southern California. I'm Andrew Schorr. Welcome to this Patient Power Program, we've got Dr. Olatoyosi Odenike, and she is from the University of Chicago. Doctor, welcome to our program. 

Dr. Odenike: 

Thank you so much for having me.  

Is It Possible for ET or PV to Progress to Myelofibrosis?

Andrew Schorr: 

A lot of people ask this question, what's the risk of ET or PV progressing to myelofibrosis? 

Dr. Odenike: 

So that's an excellent question. So, patients with ET are at the lowest risk of progression to myelofibrosis in comparison to those with polycythemia vera. So, for patients who have what we consider to be true ET as opposed to another diagnosis which is pre-fibrotic or early myelofibrosis. In patients with true ET, their risk of progression to myelofibrosis over a 10 to 20-year period is in the less than 5% range. Whereas, for those who have polycythemia vera, their risk of progression to myelofibrosis is approximately double that. Again, over a decade period. 

What Does a High Platelet Count Mean?

Andrew Schorr: 

Well, does the risk of progression to myelofibrosis from ET go up if that ET patient has a high platelet count that is not being successfully reduced with medication? 

Dr. Odenike: 

The risk of progression to myelofibrosis when you have ET associated with a very high platelet count is not necessarily higher if one is having trouble controlling that platelet count. We start to worry that the disease may be progressing towards myelofibrosis if the platelet count is coming down on its own with little to no intervention. So a decline in platelet count in someone with a prior diagnosis of ET in the absence of vigorous efforts to reduce the platelet count is actually a sign that the bone marrow is perhaps been progressively scarred down and therefore unable to be as proliferative. Some patients with ET think, Oh, this is great. I no longer need very high doses of hydroxyurea (Hydrea) or I'm on the lowest dose,” or perhaps I actually totally lost my need for use of hydroxyurea. This is great. My platelet count is now normal. That may in fact be not the case at all. 

Can Myelofibrosis Progress to AML?

Andrew Schorr: 

So now I want to go to the other endwith ET but now for me and some of my friends here, primary myelofibrosis, we worry about progression to acute myeloid leukemia (AML). What's our risk for that? 

Dr. Odenike: 

All patients who have a diagnosis of a Philadelphia chromosome-negative MPN, so that would include ET, PV and primary myelofibrosis have a risk of transformation of that MPN to acute leukemia. Fortunately, for many overall that risk is relatively low even though we are very concerned, obviously that's one of the most feared complications. For ET patients it's the lowest with the risk of transformation to acute leukemia being much less than 5%. So in the one to 2% range. For PV it's about 5%, for patients with primary myelofibrosis it's about 15%. But this is again over the course of a number of years. 

Can Certain Gene Mutations Be Risk Factors?

Andrew Schorr: 

Well, we hope so. So you touched on gene mutations. So myself and a lot of MF patients and PV patients understand that we are we're JAK2 V617F positive, and many of us take a JAK inhibitor. But people have heard about calreticulin (CALR) and MPL and others. So we have these genetic tests. What is the genetic test for any of our MPN conditions say about progression? Is it meaningful? 

Dr. Odenike: 

We are starting to understand a lot more about that, and yes it is an important aspect of trying to figure out what makes an MPN go from the chronic phase through an accelerated phase and then to a blast phase. So the accelerated phase can be an intermediate step in the transition to acute myeloid leukemia where one sees about 10% or more blasts in the blood. So in the chronic phase, typically patients will have either JAK2, MPL, or calreticulin mutation and as the disease acquires more mutations, those mutations can then fuel progression to a more aggressive state of the disease such as a blast phase. There are a number of those mutations that have been described that we can screen patients for as we monitor them for progression. 

Andrew Schorr: 

But it sounds like related to this sort of alphabet soup of genes, you're still trying to figure it out. 

Dr. Odenike: 

We know that individuals who have high molecular risk mutations such as ASXL1 mutations, EZH2 mutations, IDH1 or IDH2 mutations, mutations in U2AF1, mutations in TP53. These sorts of mutations have been well characterized as cooperating with the basic MPN mutationsSo one could have, for example, a JAK2 mutation and layered upon that one could have an ASXL1 mutation and then acquire like an IDH1 mutation. And together, these working hand in hand we think, fuel the transition to a blast phase.  

But the acquisition of some of those mutations, for example, acquiring an IDH1 mutation or an IDH2 mutation in this transition process so an acute leukemia could afford the doctor away to treat the leukemia successfully by giving the patient a drug that targets IDH1 or IDH2. So this sort of progress is in its infancy, I would say, this kind of research in terms of fueling our understanding of how to more effectively treat these. 

What Questions Should I Be Asking My Doctor?

Andrew Schorr: 

What should a patient's discussion be in their regular visits with their doctor about their concerns and maybe testing related to watching out for progression? 

Dr. Odenike: 

So my advice would be during the visit with your doctor to ask them pointed questions about that. So what are my blood counts looking like? Are they stable? Do you have any concerns that this disease could be getting worse in any way? If you have concerns that the disease may be getting worse, what are those things that you're seeing in terms of elevating that level of concern?  

So, I would suggest asking your doctor about, what is my hemoglobin doing? Is it stable? What is my platelet count? Is it stable? Is this what you expect? Or do you have any concerns that this is getting worse in some way? What is my total white blood cell count doing? And what is my white blood cell count differential doing? This is looking at the subsets of white cells to say there are many immature cells being tossed out that may raise the concern for progression. What is my LDH is that stable or not stable? Is that a concern to you in any way? What is my spleen doing? What's my weight? 

Andrew Schorr: 

I just want to summarize this with you. So let's see if I got it right. So first of all, there will be some people with ET as you suggested, may never progress, right? You said when you were early in your career she told you may just have a long life but you have ET. Then there'll be some people with some characteristics with ET where you can predict that they would progress, right? Maybe to PV or maybe to myelofibrosis, right? 

Dr. Odenike: 

Right. 

Andrew Schorr: 

Among the PV patients, they have a higher likelihood of progressing to myelofibrosis and among us with primary myelofibrosis there's about a 15% chance, 10 to 15% of going to acute myeloid leukemia. But this could be over many years, right? 

Dr. Odenike: 

That's correct. Exactly. 

Andrew Schorr: 

You guys are working on trying a lot in research to see can you stop the train or reverse it? 

Dr. Odenike: 

That's a very nice summary. Yes. 

Andrew Schorr: 

All right. Well, I want to thank you so much for being with us Doctor. You’re Terrific. 

Dr. Odenike: 

Thank you so much. Thank you. 

Andrew Schorr: 

Im Andrew Schorr. Remember knowledge can be the best medicine of all. 

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.


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