Why do MPN symptoms sometimes persist despite well-controlled blood counts? Dr. Ghaith Abu-Zeinah discusses how iron deficiency, inflammation, and disease-related symptoms can affect quality of life, and explains how looking beyond blood counts can help patients overcome barriers to effective symptom management and more personalized care.
Dr. Ghaith Abu-Zeinah is a hematologist-oncologist and physician-scientist specializing in myeloproliferative neoplasms at the Richard T. Silver MPN Center at Weill Cornell Medicine and NewYork-Presbyterian Hospital.
[ACT]IVATION Tip
"Look for other causes for symptoms, and if it is not due to another cause, clearly due to the disease, despite well-controlled counts, think of how to address some of these symptoms, either individually, if it's one symptom, or kind of in a big picture way, if it's multiple disease-related symptoms."
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Transcript
Lisa Hatfield:
Dr. Abu-Zeinah, how should symptoms and quality of life factor into evaluating how well an MPN is being managed?
Dr. Ghaith Abu-Zeinah:
Yeah, so this is a very important point. You know, if you have a disease and you attribute the symptoms to the disease, you are treating the disease with the goal of both improving symptoms and blood counts.
Yet in not even some, in many instances, we have control of blood counts, but we still have symptoms. So, I think, again, this is one of those two possibilities in my mind. One being, if your disease is truly adequately controlled, perhaps your symptoms could be due to another process.
So, have we done a thorough enough evaluation for other things that could explain your symptoms? And one thing that tends to actually happen quite commonly, at least in PV, is that patients might have hematocrit control, platelet control, white cell control, but be very iron-deficient, because in the process of getting there, they may have had a lot of phlebotomies that drained them of iron.
And the fact that, you know, the patient’s iron-deficient can induce a lot of symptoms that might even mimic disease-related symptoms, whether it be fatigue, brain fog, just weakness, even neuropathy symptoms sometimes.
So, I think that identifying iron deficiency clearly as a byproduct of having PV, and addressing that, and actually repleting iron when you know it’s safe, right? If your patient is relying on phlebotomy, then repleting iron goes against that strategy, but that’s one of the reasons I don’t like the phlebotomy-only strategy.
Because I would like to control hematocrit counts in a way that doesn’t necessitate being iron-deficient and living iron-deficient for years to decades. So identifying other causes of symptoms, I think, is key here, besides the actual disease. Now, you know, assuming that there is no other driver, and this is clearly disease-related.
Controlling counts typically controls what we refer to as microvascular or vasomotor symptoms, so things that relate to blood vessel flow, you know generally tend to improve with count control.
But there are cytokine-driven symptoms, and so cytokines are these signaling molecules that cause inflammation unnecessarily in different organs.
And that can really induce fatigue, it can induce weight loss, night sweats, and your counts might look perfect, but you still have these cytokines triggering all sorts of symptoms. And a good example there is myelofibrosis, because in myelofibrosis many patients, actually most patients, tend to not have very high counts, meaning, the high platelets or the high hematocrit is really more of an ET and PV and maybe just prefibrotic MF issue, but typically more advanced overt myelofibrosis, we tend to deal more with either normal platelets or low platelets.
And so that’s a good example of where numbers might appear within range or stable, but symptoms are increasing. And that’s, you know, a good example of where cytokine-driven symptoms might be most pronounced.
And we talked there about what are the therapies that truly improve symptoms. We know that we have JAK inhibitors available for the treatment of myelofibrosis, actually four of them that are approved in the U.S.
And we know that in all the clinical trials that symptom management is monitored closely, either as a primary endpoint or a key secondary endpoint.
And so we look for patients to really have symptom improvement in addition to the other primary endpoint of spleen size improvement, and really other parameters improving, whether it be hematologic, bone marrow, or even molecular findings.
So I think I think there is a lot more to symptoms than just blood counts, that’s for sure. And we need to search for other causes. I guess I’m getting into my [ACT]IVATION tip is look for other causes for symptoms, and if it is not due to another cause, clearly due to the disease, despite well-controlled counts, think of how to address some of these symptoms, either individually, if it’s one symptom, or kind of in a big picture way, if it’s multiple disease-related symptoms.