Diagnostics and Risk Stratification for Patients With Polycythemia Vera
Expert Roundtable Part 1
Expert Roundtable Part 1
In this 4-part expert roundtable series, Claire Harrison, MD, Guy's and St Thomas' NHS Foundation Trust leads a discussion on polycythemia vera (PV) and the importance of hematocrit control with Jean-Jacques Kiladjian, MD, Saint Louis Hospital, Paris, and Alessandro Rambaldi, MD, University of Milan.
The first video of the series explores diagnostics and risk stratification for patients with PV.
Transcript:
Claire Harrison: Welcome to Oncology Learning Network. My name is Claire Harrison. I work at Guy's and St Thomas' in London in the UK. I will be moderating today's discussion on polycythemia vera and the importance of hematocrit control. I'm joined today by a distinguished panel of experts and colleagues. We've been working together for a long time now.
Perhaps you'd each like to introduce yourselves and tell us a bit about your roles. Professor Rambaldi, could we start with you please?
Alessandro Rambaldi: Hello. My name is Alessandro Rambaldi. I'm a professor of hematology at the University of Milan and I'm working at the Papa Giovanni Hospital in Bergamo. I've been involved in some clinical trials on chronic myeloproliferative neoplasms, and so this has been part of my career.
Claire Harrison: Thank you so much for joining today. Jean-Jacques, lovely to have you here. Could you introduce yourself, please?
Jean-Jacques Kiladjian: Hello, Claire. Hello, everyone. My name is Jean-Jacques Kiladjian. I work in Saint Louis Hospital in Paris where I take care mostly of patients with myeloproliferative neoplasms. I'm at the head of the MPN Comprehensive Center of Saint Louis. That includes the biology lab, the outpatient clinic, and also the clinical investigation centers where we do clinical trials in MPNs.
Claire Harrison: That's fantastic. I want to thank you both again for joining today, and also thank you for your contributions over many, many years in this field. Today, in this section we're going to talk about diagnostics and risk stratification of PV. So, recently we had 2 new updated risk diagnostic criteria for polycythemia vera.
Jean-Jacques, how does a patient usually come to you and which diagnostic criteria do you use?
Jean-Jacques Kiladjian: Well, as you mentioned, we have now 2 classifications that hopefully for MPNs are very close and virtually the same, especially in PV. The WHO classification just discarded the red cell mass determination because I think it's no longer available in the United States. I don't know about England and Italy, but in France we can still use it if needed.
We have the international classification that kept the same criteria that we use for a while. So, usually when patients are referred for a diagnosis of PV in our center, first we confirm the erythrocytosis, either with very elevated blood counts, hematocrit hemoglobin, or with red cell mass in patients in whom we suspect mass PV. Maybe we can discuss that entity later.
Then we search for the JAK2 mutation first. Sometimes also search for the serum EPO level for the patients because it's in the same blood, almost in the same blood puncture, so you can do both tests, and then discuss after the results if we have to do the bone marrow biopsy or not. It's not always done, I should say, in France for all PV patients, especially in elderly patients.
If we have an elevated hematocrit hemoglobin and JAK2 mutation positive and EPO level low, usually we don't confirm with bone marrow biopsy. But it's still done in younger patients looking sometimes for some degree of fibrosis that can give you a kind of prognostic value for the future of the patient.
Claire Harrison: Well, thank you. It's interesting to reflect that. We also can still do a red cell mass in the UK, but we did decide to cross it off in the WHA, and I must admit I tend to use it a little bit later if I have a JAK2 negative patient or maybe a patient where I think the diagnosis might be a masked PV.
Alessandro, do you find that you make a bone marrow biopsy for most patients and how would you use the red cell mass?
Alessandro Rambaldi: I try to perform a bone marrow biopsy in younger patients. Not necessarily at exactly the diagnosis, but to be ready to do it within a reasonable period of time. Particularly for those patients who may be eligible for clinical trials and those for whom we would like to have an accurate history of the bone marrow biology in perspective.
We try to omit it just in the elderly patients, and we do not perform the red blood cell mass as a standard diagnostic approach. I like to put some attention in those few patients who are JAK2 negative in identifying possible reasons of mass secondary erythrocytosis. So, personally I try to put much attention to investigate this point, particularly in younger patients. I do regularly perform the erythropoietin evaluation in the plasma.
Claire Harrison: Yes, actually Jean-Jacques, you and your colleagues recently published a big article showing that actually a very low serum EPO level was very predictive of PV, especially in the presence of a JAK2 mutation, so I wanted to call out that work. I think it's really helpful.
So, could you just touch on a masked PV? How do you think about that? What do you think that is? For me, I think it's a PV patient maybe where we missed because the iron level was too low, or they evolved over time. But in Hospital Saint Louis, what does that patient look like? And then Alessandro, I'll probably come to you and ask you about risk stratification.
Jean-Jacques Kiladjian: Yeah, sure. I think we don't diagnose so frequently masked PV because we unmask it with the red cell mass evaluation, so usually it means you may find this situation, for example, in patients with portal vein thrombosis who have portal hypertension. Their blood counts are low. They don't reach the threshold of hemoglobin or hematocrit that are in the WHO for PV, but indeed they have PV if you measure the red cell mass or do the bone marrow biopsy.
It's important to diagnose this entity that may present like ET [essential thrombocytosis], for example—may mimic ET sometimes, in patients with only apparently elevated platelet count. And, the diagnosis is corrected by the bone marrow biopsy for this particular entity. Because why is it important? Because the vascular risk is different and mass PV has a higher risk of vascular event than through ET, so it's important to rule out this entity when you suspect it.
Claire Harrison: Yeah, I totally agree. I think JAK2 positive ET patients who sometimes have a borderline hematocrit, this is quite tricky—and absolutely splanchnic vein thrombosis.
Alessandro, I mean, you are working in Bergamo and Bergamo did a lot of the seminal work and published a lot of really important data in PV. Tell us how you risk-stratify a patient with PV in your practice.
Alessandro Rambaldi: For the time being, we remain on the conventional risk stratification based on age and previous history of thrombosis. I think that this is something that remains a key point. Of course, it's possible that new insights will come from a deeper knowledge from the biology, but the clinical evaluation of the patients and the age and the previous thrombosis remains the mainstay for us.
Claire Harrison: Yeah, absolutely. But I think there's a few tricky areas, aren't there? Like what do you do about a hypertensive patient? We'll come to cardiovascular risk assessment later—but I'm just interested, do you weave in the white cell count at all, or—
Alessandro Rambaldi: Of course. The history of white blood cells has been for a long time a focus of our investigation, but this has not yet been translated into different clinical management, particularly in the setting of clinical trial. Perhaps this will happen in the near future.
Claire Harrison: Yeah, because that's been quite strongly linked to disease evolution as well as also to thrombotic risk. I think it's really important.
Alessandro Rambaldi: Right, right.
Claire Harrison: Jean-Jacques, we've recently been looking across some PV patients and thinking about how do we do cardiovascular risk stratification and assessment. I found out that we do this in a slightly different way, and I think you do it in the best way, so tell us how you do that in Hospital Saint-Louis.
Jean-Jacques Kiladjian: I'm not sure it's better, but, yeah, it's different. Well, we have a quite aggressive and proactive attitude regarding cardiovascular assessment of all patients with PV regardless of age. Obviously the older they are, they're usually already followed by a cardiologist sometimes or they already had some cardiovascular events.
But even in younger patients with absolutely no history of cardiovascular events, we frequently refer them to a cardiologist, not any cardiologist, but a cardiologist that knows what we are looking for, that these patients are at high risk of cardiovascular problems in the future, that they will be followed for decades and we need this proper assessment.
At least an echocardiogram, doppler of arteries, peripheral arteries, is performed. We ask to perform that for almost every patient at baseline and then regularly every 2 to 3 years in patients without any risk factors, more frequently if needed. So yes, we have a quite very proactive attitude against these additional factors because we also noticed that—and maybe this is a field for the future as Alessandro said—that it's not exactly maybe the same risk factors for arterial versus venous thrombotic events.
Maybe some characteristics of the disease, of the patients, may predispose more to arterial events that are more dangerous for the patients like myocardial infarction, stroke, et cetera, and these risk factors may be different. And the cardiovascular, let's say landscape of the patient at baseline is very important to avoid and to prevent these arterial events.
Claire Harrison: That's really helpful. And maybe a word from you, Alessandro, about how is this done in Bergamo?
Alessandro Rambaldi: I think that what Jean-Jacques said, it's very important and is very provocative. Because I believe that we should move ahead from the old patient risk evaluation that was established several years ago. But then comes the problem of performing studies to see whether a different therapeutic approach made an impact on this—particularly on the cardiovascular events—without, and avoiding, any unnecessary side effects related to an early activation of a treatment. So, I think that this is something that should be addressed by prospective trials.
Claire Harrison: I also think there's a lot to be said for patient education with regards to cardiovascular risk assessment, too. Anyway. That was a really very nice discussion, so thank you very much for joining us for that discussion on diagnostics and risk stratification.
Please join us for our next discussion on aims of treatment and choice of first-line therapy.
