Facing a Cancer Diagnosis: Advice From An Expert

Facing a Cancer Diagnosis: Advice From An Expert from Patient Empowerment Network on Vimeo.

Brittany DeGreef, a genetic counselor, provides essential advice for when you are facing a cancer diagnosis emphasizing that leaning on supportive friends and family is key.

Brittany Degreef is a Genetic Counselor at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. More about this expert.

See More From the The Pro-Active AML Patient Toolkit


One piece of advice I give patients who are just diagnosed with cancer – and we do frequently see patients at least once a week who were just diagnosed either that week or the week prior – is feel what you need to feel. Not every patient is going to react or cope with their diagnosis in the same way as someone next to them, even within the same family. That also goes for caregivers and relatives.  

 So, just because you feel like helping out a relative in a specific way, it might not be the same for your brother or sister or cousin.  

 So, we always tell patients that there is no wrong or right way to cope with a diagnosis of cancer. The way that you approach it is perfectly fine and there’s no right or wrong way to do that.  

So, another piece of advice we always tell patients is don’t be scared to lean on your support network, whether that be family or friends, your healthcare provider, advocacy groups, never be afraid to ask for help.   

And for some patients who feel like they have limited resources, usually hospitals where you’re receiving your patient care has many resources available to you, whether that be emotional, financial, spiritual, logistical. Don’t be scared to ask about those resources. 

Barby Ingle – What Advice Do You Have For Someone Who Is Newly Diagnosed?

As the president of the International Pain Foundation, a best-selling author, and chronic pain advocate, Barby Ingle shares her advice for the newly diagnosed. For all our A Conversation With… videos please click here.

Barby Ingle – What Advice Do You Have For Someone Who Is Newly Diagnosed? from Patient Empowerment Network on Vimeo.

Ask the MPN Expert – Dr. Joseph Scandura

Ask the MPN Expert – Dr. Joseph Scandura from Patient Empowerment Network on Vimeo.

MPN specialist Dr. Joseph Scandura from Weill Cornell Medicine answers patients’ burning questions.


Greetings from southern California. I’m Andrew Schorr from Patient Power. Welcome to this Patient Empowerment Network program where you can ask an MPN expert your question. I’ve been living with an MPN, a myeloproliferative neoplasm myelofibrosis, since 2011. So, believe me, I have questions and I want answers just like you. I want to thank the Incyte Corporation for its financial support, but tell you, of course, that all the editorial control is our expert and our producers and me. Nobody tells us what to ask or what to say.

Okay, let’s meet today’s MPN expert. Joining us from New York City is Dr. Joseph Scandura. He is with Weill Cornell Medicine in New York City and he is also the scientific director of the Richard T. Silver Myeloproliferative Neoplasm Center at Weill Cornell Medicine. Dr. Scandura, welcome and welcome back to Patient Power. We’ve had you before. Thanks for being with us.

Dr. Scandura:
Thanks for having me, Andrew.

Okay, and I should mention that Dr. Scandura is a physician-scientist, so you can see that whiteboard behind him. He spends time in the lab, as well as seeing patients, in-patients, and in clinic. So, he is meeting us, but also working on a cure and we’re gonna talk more about that and hopefully, we can get there. Okay, are you ready for our first question Dr. Scandura?

Dr. Scandura:
All set.

Okay. So, this one comes from Philip who writes and he says, “I’m a 63-year-old male with PV, polycythemia vera. What does it mean that my blood is too thick?”

Dr. Scandura:
What it’s probably referring to, the term too thick is a little bit – can be generalized in a lot of different directions. It’s a colloquial term, not really a medical term, but what people often are referring to there in the context of polycythemia vera is too many red blood cells. If you think of the blood vessels in your body as being highways, they can only accommodate a certain amount of traffic. And you being in southern California are probably aware of this, that sometimes there’s too many people trying to get on the highway at the same time and that slows everything down. You could consider the highways too thick in that situation and that’s what’s really happening in polycythemia vera.

There’s too many red blood cells. There’s about 1,000 red blood cells for every of the white blood cells there, so the most common blood cell type and they occupy about half of the whole blood volume. And when you have too many being produced, they end up causing traffic jams in the blood vessels and that is what people are trying to describe when they’re saying the blood is too thick.

And you’re at risk for stroke and blood clots?

Dr. Scandura:
Yeah. So, it has a lot of both short-term and long-term consequences. Short-term certainly it provides a risk of having abnormal blood clots. That can be in an artery, so that could be a stroke, an artery in your brain, or an artery in your heart, a myocardial infarction or heart attack. It can also be a clot in a vein and so these, I’m sure you’ve seen them on TV, the advertisements for DVT or deep venous thrombosis or pulmonary embolism which is usually a clot in a vein that then has broken off and traveled through the circulation and landed in the lung where it can cause symptoms there. And so, the short-term risks of a clot are certainly elevated in people with polycythemia vera when the blood counts aren’t controlled.

Okay. Just one follow up question. Philip was wondering about this too. So, we see ads on TV whether it’s the DVT medicine ads or the blood thinner ads. Does that apply to people with PV?

Dr. Scandura:
It can. We treat people with PV to reduce the risk of a clot, but some people are diagnosed with a clot at the same time they’re diagnosed with PV and some people, even with the best of treatment, end up developing a clot. If it’s a clot in the vein, then one of the things that is a standard of care is to administer drugs that colloquially again are referred to as blood thinners. In this context, it has a different meaning and this is a group of drugs that interfere with the blood clotting system. So, these are proteins, not cells, and it’s what – if you ever have cut yourself and you feel just with your fingers, it gets a little sticky between the fingers. That’s actually clotting.

It’s a little bit like Jell-O. It starts out liquid and then it solidifies and that’s what your body does to help prevent bleeding. It forms this sort of polymer fiber that ends up being part of the plug. And what the blood thinning medications, the so-called blood thinning medications, do is they interfere with that process. Either given by injection or given by pill, the ultimate goal is to reduce the formation of that sort of sticky acellular clot. And that’s more of a treatment and can be a preventative for future clots as well, but it’s a little different than what we were talking about before in terms of too thick blood from too many red blood cells.

Too many cells versus the quality of the cells.

Dr. Scandura:
Yeah, but not even the cells. A lot of the blood clotting factors are produced by your liver. They’re not from the cells themselves that are floating around in the blood.

Andrew: I’ve never understood that before. So, thanks for explaining. I should also just say one thing about Philip. He shared with us that he has AFib. So, when somebody, and that’s not uncommon atrial fibrillation, does that complicate all the treatment for somebody with PV?

Dr. Scandura:
Well, one of the risks with AFib, some of them can be just related to the heart, it can disturb a little bit in how the heart functions and if people have some mild symptoms, AFib can make symptoms worse just from a heart function standpoint. But one of the things that’s related to, again some of the commercials you see on TV and the rationale for blood thinners, is the heart – the atrium, the left atrium which is really what fibrillates, which is just – normally the heart is pumping like this, all together coordinated. And what fibrillation means is it’s sort of not doing that. It’s going like this and what happens is the blood and the surface of the heart ends up not being pushed out normally.

And sometimes actually clots can form on the surface of that fibrillating heart and then when they get pushed out, they can travel. And because it’s usually the left atrium where this happens, when they travel they go into the arteries and then they can form clots and that can be stroke is the big thing people worry about. So, you can have atrial fibrillation that puts you at risk for stroke and that’s why people think about anti-coagulation medications to prevent that risk. And so, again, that’s another rationale for blood thinner, although it has nothing to do with the blood being too thick. It has to do with atrial fibrillation itself.

Okay. So, two things going on. Here’s a question we got in from Julie. Julie says, “What is the significance of a very low allele burden in a JAK2 positive patient?” And may you could define allele for us too.

Dr. Scandura:
Sure. So, as you know, we have some of our genes from mom and some of our genes from dad and the genes that we get are always in these two copies. And so, one copy from mom, one copy from dad, and they’re mixed and matched while we’re being sort of grown up from the embryo. But what happens in MPN is sometimes one of those copies, always starts with one of them, becomes mutated and that can be for instance, in the most common mutation, in the JAK2 gene, JAK2 V617F, a particular mutation that’s associated with abnormal function of the JAK2 gene product. And so, if we have just one copy in a cell, then one copy’s normal and one copy is mutant.

So, if we are talking about that one cell, that variant allele frequency, so that’s the abnormal gene. The proportion of all the genes that are abnormal would be 50%. Right? One abnormal, one normal. But now we think about all of the blood cells, trillions upon trillions of blood cells and then we have to take sort of an average of all of those cells. Some of them will be normal, some of them will be MPN cells, some of them will have one copy normal, one abnormal, some two abnormal, and some both normal. And so, when we look in a composite from a blood draw which is generally what people are sending, it’s a representation of how many abnormal alleles are present among all of the alleles of all of the DNA from the blood cells that’s been selected.

So, what a low variant allele frequency means that the proportion of mutant alleles in that sample of your blood is low. So, low would be maybe 10% or 5% or something like that and what is the significance of that? It’s an area a little bit of some debate, but there’s certainly a number of studies that have shown a correlation between the variant allele frequency in blood and the disease type itself. So, for instance, essential thrombocythemia, or ET, generally has a lower bearing allele frequency than myelofibrosis for the same mutation. And polycythemia vera is often in between.

While we’re talking about genes, I just wanted to bring in this question from Jocelyn because we’ve been learning are we JAK2 positive, are we CALR positive, these others that you’ve been discovering. So, Jocelyn said, “In 2006 I tested positive for JAK2 V617F. In 2018 I was told that I’m not JAK2V617F positive, but that I’m CALR positive. So, is it common for mutations to change and what does it mean?”

Dr. Scandura:
So, it’s not common for the mutations to change in terms of going away if they’re present, although there are certainly examples of this happening. It’s not common. What is probably a little bit more common is sometimes people have one mutation or a couple mutations and then sometimes more mutations are found later. And that often, not always, is linked to the disease changing its character itself. So, somebody with polycythemia vera having more of a fibrotic phase of the disease. In this situation, it’s a little hard to know exactly what happened, but there is a fair amount of variability from one laboratory or one test type to another in terms of sensitivity and the specificity of what is being detected.

So, JAK2 may have been at a very, very low level, could have been an erroneous measure, or it could have been at a relatively low level and the calreticulin mutation wasn’t tested for. And then later somebody retested with a different test that wasn’t sensitive enough to pick up the JAK2 mutation and they looked for a CALR and now that’s coming up positive.

So, the testing modality, the type of test that’s being done, and its individual sensitivity is an important part of this story and it’s a little hard, I think even for many physicians, to sort of get their heads around because it’s not like a blood count where you have international standards and basically a half-dozen equipment makers everybody uses across the world. There’s a lot of different technologies, each of which have little wrinkles to them that can limit somewhat exactly what’s being reported.

Okay. Here’s another one we got. This was actually asked by several people. Nick, Maggie, and Philip all want to know related to phlebotomy. What are the goals of phlebotomy as a treatment and how does it work and when do you know when it’s time to switch from phlebotomy to medication?

Dr. Scandura:
Right. So, I just came from a conference the end of the week and this is a topic of debate among physicians. When, whether to do phlebotomy? Whether phlebotomy therapy by itself is sufficient? What are the alternatives and when to make those decisions? I would say, I can tell you what my own feeling is. I feel that there is good support to justify that, but to be totally honest, there are physicians who feel differently than I do and I don’t know if any of us can claim to be absolutely correct. But I think we can all agree that the goal of phlebotomy in the short term is basically to take cars off the highway.

If you go back to the analogy of having too many cars on the highway causing thickened blood or this sludging from the red blood cells, this is a therapy specific to polycythemia vera, is that phlebotomy is just a very simple way of taking blood out of the system, taking cars off the highway. So, if you were to imagine and I frequently imagine this in New York City, is all of the sudden a third of the cars disappeared, it’d be a lot easier to get around. And so, that’s really what the goal of phlebotomy is, is to make it a little easier on your body to pump the blood around because there’s less resistance to having all that traffic in the vessels. How much? Go ahead, you had a question.

I was just gonna say, but debate about when to leave phlebotomy behind and have medication try to do the job when you prove one or others that may be coming.

Dr. Scandura:
So, I think the first goal is to get people under what would be considered control. So, an adequate level of traffic. And the numbers that are generally accepted by people in the field is having a hematocrit, that’s the portion of blood occupied by red blood cells, in males it’s below 45% and in females below 42%. Although we can all argue about that a little bit. I think people settle down around those numbers.

When is too much? My personal feeling and this is where there isn’t great data, so you’re left with opinion, but my personal feeling is it depends a little bit on the patient, the convenience, and I find that people who are getting phlebotomy more than four or five times a year, it ends up being a real burden on them in terms of the amount of time that they’re having, poor control of their polycythemia vera, and the amount of time required for phlebotomy, and the amount of risk of things like iron deficiency which can cause symptoms.

And then there’s some suggestion, I wouldn’t say great data, that maybe iron deficiency or repeated phlebotomy may be a risk in the long term, although I think that data is not very clear. My biggest determinant is patients, in my experience, just get a little fed up with getting phlebotomy when it gets above four, five, six times a year.

Okay. Thank you for that. I should mention to our audience again if you want to send in a question, whether we can use it on this program or a whole bunch we’ll be doing coming up, send it to mpn@patientpower.info. Okay, so here’s a question we got from Nick and all of us wonder about it. How often or do we need bone marrow biopsies so that you, as our doctor, and we are well informed about what’s going on?

Dr. Scandura:
So, another area where there isn’t – you know, in medicine we look for the perfect data. We’ve controlled – we treated one group of very similar patients one way, we’ve treated another group of people another way, and we compare and see who does better. What’s the better approach? This hasn’t been done for how often to check bone marrow. I think bone marrow evaluation is very important. Personally, I generally follow how the patient is doing as the primary determinant and if there are any signs that something is changing. And those signs can be how the patient is feeling, new symptoms that are arising, but oftentimes it can be just in how the blood counts are responding.

You’re on a stable dose of a medication for several years and all of a sudden it stops working or all of sudden it starts working too well. You have very low blood counts whereas before you were okay. That suggests to me something’s changing. The bone marrow is the factory for all the blood cells. So, if you wanna know what’s happening with the production in the factory you really have to look into the factory and see what’s going on. And so, that’s my personal threshold for doing a bone marrow, when I’m seeing something that’s suggesting that the factory is not functioning the way it was the last time I looked.

Okay. And for those of us who’ve had many bone marrow biopsies, and I have, hopefully where it’s done is someone who does it frequently. Usually, the anxiety we have is worse than the exam itself. It takes 15, 20 minutes, whatever and someday I’ll tell you the story of the lady down at MD Anderson who believed in voodoo and talked to the bone marrow as she was pulling it out. And it was so weird, that I was so distracted, I didn’t feel a thing, but anyway I understand it’s important.

Here’s a question that will help our friends with ET. This is from Michelle. She says – well actually now she has post-ET myelofibrosis. She says she has ASXL1 and TP53 gene mutations. Does the mere existence of these predict aggression and poor outcome? That’s what she worries about that those have been found.

Dr. Scandura:
Well, obviously every individual has their own history that they’re developing and so exactly what this means for you, for an individual, is different than what it would mean for a population of people with similar mutations. That’s really what we know in medicine. We look at people in a cross section and we say people who we can put into this bin tend to behave in that way, but within that bin, there are individuals who don’t act that way, the way that the others do. So, I would in myelofibrosis, in MDS, in polycythemia vera, P53 mutations are an area of some concern, as is ASXL1 mutations are also an area of some concern.

In ET it’s less well established and so I think because, if this was just ET and you had those mutations, I think many people, myself included, would say well, maybe we don’t know perfectly, but it is an area of some concern. I’m gonna keep a closer eye on you. Now that it has already evolved into myelofibrosis, I would say this is probably more like myelofibrosis where we know that P53 mutations, TP53 mutations, and ASXL1 mutations, can sometimes be some of the harder ones for us to treat. It’s something that, if an allogenic transplant is something that is possible, should at least be considered and discussed.

It doesn’t – speaking with a transplanter, getting typed doesn’t mean you have to get a transplant, but it gives you information and so I think that that would be a reasonable thing to do. Again, the decision at the end, it may not be the right decision for you, but it is something that is information for you to use in making informed decisions.

Right. I did have a consultation with Dr. Castro, who was at the time here in San Diego, exactly about that. Not to take action, but just to have the relationship and be typed, et cetera. Here’s a question we got from Paul. He says, “I was diagnosed in 2009. I take a weekly dose of 90 mg of interferon. How long can a patient continue to take interferon and what indicates a move to change treatment?”

Dr. Scandura:
So, we have people who have been treated for 20 plus years with interferon. So, I don’t know if there is a known duration which is too much. For many patients it’s a very well tolerated therapy, can be quite effective, and I think that it is one of the few medications that seems to have some disease-modifying activity. However, when to change? If it looks like it’s not working, it’s time to think about changing and that can be adjusting the dose, but I think if somebody has been on it for a long while, that’s when I think thinking about additional therapy, either adding another medication to the interferon or changing completely to a different medication.

Clinical trials, there’s a lot of activity in MPNs in clinical trials. Thankfully, over the past five years or so, it’s really been increasing. There’s a lot of options. There’s some drugs that we’re really pretty excited about right now in terms of thinking they might have some nice activity and talking to somebody about what might be a suitable treatment for you if the interferon was not working anymore.

Okay. Here’s a – again we’re getting similar questions from a number of people. So, Ragita, Nankin, Raven if I’m saying the name right, and Jacquelin sent in basically this question. How common is it in patients with MPNs to have bone pain? What causes it? Is there anything that can help with the pain?

Dr. Scandura:
So, bone pain is always on the list of symptoms reported by patients with myeloproliferative neoplasms. I wouldn’t say, in my experience, it’s one of the more common ones. It might be a little bit more common early in disease. Sometimes things like phlebotomy that you can actually have a rebound where the bone marrow is a little bit revved up to try to replace all those cells that were taken out, that can cause some bone pain. It can be seen in myelofibrosis occasionally and sometimes when the disease is becoming more aggressive or is having a – changing its pace. But the cause of bone pain, we think of as being related to sort of expansile pain.

So, the bone marrow, the factory for all the blood cells, sometimes is just working so hard that it causes, it irritates the bone fibers that are around the surface of the bone. There’s very little in the way of pain fibers inside the bone, but on the surface of the bone you have a lot and that expansile pain, that gives that sort of vague, achiness people often describe as bone pain. The treatment for bone pain in some ways is determined by what the cause is. If it’s just, for instance, a rebound after phlebotomy, it can last a day or two and then go away. And so, short-term symptomatic treatment with non-steroidal anti-inflammatories, NSAIDs like Motrin, can be helpful or Tylenol even.

But occasionally patients report a real benefit from things like histamine blockers which the mechanism for that is entirely unknown, but there’s certainly a population of patients who feel like the bone pain has gone away with medications like Claritin you can get over the counter. It’s worth a try. They are very well tolerated medications and not all patients have any symptomatic benefit, but a subset of people do. If the bone pain is related to the cells being too active, a very proliferative feature of the disease, sometimes it dictates treatment.

So, if you were on phlebotomy alone, well maybe it’s time to change to a more cytoreductive therapy and see if that can help with the pain. Sometimes it prompts additional evaluation. If you’ve never had bone pain, all of a sudden the blood counts are a little different, you have bone pain, it might be something somebody would think about doing a bone marrow evaluation for. Again, looking in the factory which is probably where the cause is coming from.

I have a couple more topics I want to cover just before we close. We’ll go just a little bit longer if that’s okay. So, Robert wrote in and said, “How does a stem cell transplant cure myelofibrosis?”

Dr. Scandura:
So, I’ll go back to that factory analogy. If you think of the bone marrow as being sort of corrupted by these MPN cells. You have, normally this is a very orderly factory. It’s producing a number of different lines if you think of it as a car factory. You can be producing red blood cells maybe your sports cars, and your white blood cells, your infection-fighting cells, as sedans, and platelets as SUVs, but it’s all very orderly and it should be proceeding in a regular way. And you get MPNs and somebody has just turned up the volume and are just cranking out a lot of cells. And sometimes that production starts becoming abnormal too and that’s more like in a myelofibrotic setting.

And so, what is the point of a stem cell transplant is really to clear out that factory, get rid of all the workers in there, and replace them with completely different workers to come in, set up shop, clean up the factory, and start normal blood cell production. There’s another part of it is, it’s not just the blood cells, it’s actually the immune system. And so, you’re giving the recipient an entirely new immune system. You have to wipe out the old immune system to allow the new donor cells to get a hold in the bone marrow and then they have to be educated to sort of relearn how to fight off infections and to figure out who is who.
So, graft versus host is one of the complications where those cells from another person come into the recipient and say, “Ah, I don’t know you. I’m going to attack.” And so, that can be a problem. It can be a short-term problem. It can be a long-term problem. It can be mild and it can be severe, but there’s another edge of that sword which is what we think of as graft versus leukemia effect, or in this case it would be graft versus MPN effect where some of those donor cells recognize the little differences between them and the MPN cells and wipe them out. And so, that’s really what you’re trying to do is allow that new immune system to find the bad actors and wipe them out.

Okay. You touched on something I think we’ve got to ask about and that is people are hearing in the blood cancers now the experimental and in some cases an approved approach called CAR-T, chimeric antigen receptor T-cell therapy, but again immunotherapy to train the T-cells to fight your ailment. What do you think about that in MPNs? Does it have promise?

Dr. Scandura:
I mean, it definitely has promise. It’s been a challenge in myeloid disease as a whole, so AML, MDS, MPNs have not been the first diseases where this has been shown to be successful, more lymphomas where it has had a lot of traction and some nice responses. What it really is it’s a living drug and this can be done in a couple different ways. They can be cells from yourself that then are treated in the laboratory so that they start recognizing these immune cells. You start tricking them into saying, “I’m going to attack this particular thing.” Even though they weren’t really trained to do that, they are now being tricked into doing that.

And so, in a disease like a B-cell lymphoma, most of them express a particular protein that’s on B-cells, CD19. So, if you take these CAR-T cells and you say, “Well, go out and kill everything you see that has CD19 on it”, it will wipe out a lot of those lymphoma cells. In myeloid diseases like MPNs, it’s a little harder. The targets are not so clear-cut and they’re shared with normal cells. There’s one area where I think it has the most promise is calreticulin because the mutation in calreticulin isn’t a tiny little mutation. It’s a mutation that causes a whole new end of the protein that doesn’t exist in the body otherwise.

And some of the calreticulin actually gets onto the surface of the cells so it’s displayed to the immune system, and so this is an area where I think there’s some promise for CAR-T cells to target those calreticulin mutant cells. There may be other targets as well and I think we’ll learn as time goes along. People are trying to target molecule CD123 which is expressed on certain abnormal stem cells. The problem is it’s expressed at relatively low levels on those cells. It’s also expressed on normal cells and it’s expressed at higher levels on much more common cells. So, it makes it a somewhat imperfect target, and also difficult from a drug standpoint because there’s a lot of people wearing the same mask, only some of them you want to kill. So, it can be a problem.

Okay. You have quite the analogies. But, I’m just gonna ask you about two more questions and then we’re gonna have to go. This came in from Linda who says, “I am CALR positive and I have many symptoms. What causes vision symptoms for me and migraines? Can that be tracked to the CALR somehow?”

Dr. Scandura:
It’s common in a subset of people with MPNs. Sometimes it’s linked to the platelets themselves, to the white blood cell count, so I would certainly unless there’s a reason not to try aspirin, that’s something that can help with patients. It may also be an indication for cytoreductive therapy, so actually trying to lower the blood counts. I don’t know exactly what disease that Linda has, but it’s one that I would think is a symptom that would warrant therapy because it can be quite bothersome.

The vision changes is something that may be related to the migraines, but it’s also something that might prompt a visit to an ophthalmologist so they can actually look at the blood vessels in the back of the eye and sometimes what happens is you can have a little irritation of the blood vessels or even clots in those blood vessels and that’s something that would definitely trigger a change or new therapy.

Dr. Scandura, our audience is saying, “Please, one more question, one more question.” So, if I can a couple more. Philip said, “Is iron deficiency a new normal if you have PV and you’ll, therefore, have weakness, fatigue, maybe even some cognitive issues because of anemia as well?”

Dr. Scandura:
Yeah, so I sort of fall in the camp, as I mentioned before, there’s some debate in the field and I sort of fall in the camp that if you’re getting symptoms from iron deficiency, it might suggest that something other that phlebotomy could be beneficial or could relieve that symptom. Everybody, if you take enough blood out of them, is going to become iron deficient and, in fact, most people diagnosed with polycythemia vera, if tested, actually meet the criteria for iron deficiency, not because they actually don’t have enough iron in their body, but because all of the available iron is soaked up in making red blood cells. Red blood cells are red because of iron.

So, if you think about all of the iron in your body and all of the places it’s used for metabolism and everything else, there’s a lot of enzymes that actually use iron as part of their catalytic site. A large proportion of all of the iron in our body goes to making red blood cells. In polycythemia vera, that regulation is completely abnormal and you end up just making a lot of red blood cells that aren’t needed and it soaks up all the iron. Then when you start doing phlebotomy, you’re taking all of that extra iron and you’re taking it out, but the bone marrow still wants to try to make red blood cells. So, it continues to scavenge as much of the iron as it can.

So, iron deficiency is pretty common and if you need a lot of phlebotomies it’s universal. Some patients, in my experience, meet all the criteria for severe iron deficiency have very little in the way of symptoms. Others meet criteria for mild iron deficiency, but they’re quite symptomatic. And so, in those instances, you need to individualize a little bit. At least give a try to a different therapy and allow the iron stores to normalize and see if that improves the symptoms.

Okay. You used the word individualize and that’s where I wanted to wrap up. So, you alluded to earlier, that you were encouraged by new medicines coming for MPNs and you have your whiteboard behind you where you’re charting things and I hope, Joe, coming up with a cure of tomorrow for all of us. How encouraged are you in the near term and the longer term for beating back or even curing these diseases?

Dr. Scandura:
I think we’re gonna cure these diseases, I do. I don’t know if it’s gonna be this year, but I think that the number of tools we have to understand how these diseases work and the number of new drugs that are being developed that have real promise, like real mechanistic reasons why they should work, I think is going to yield, reap rewards over time. People have heard this for a long time. The war on cancer has been going on for a long time, but I think we didn’t have the tools that we have now for that entire duration. Right now, we can sequence a genome in a week of a person. Now, do you need to do that? No, but it allows you to get a level of information that was in the past, really just fantasy world, science fiction, and now it can be done on a routine basis.
There are, virtually all of our patients, have sequencing for 40 plus genes. It allows us to know a little bit more about what their risks are, and also gives us a spectrum of targets to start hitting. There’s models that are better than what we’ve had in the past for many of the cancers that have been targeted. Breast cancer models, you know, there’s some decent breast cancer models, but they’re very complex tumors. MPNs, for better or for worse, if you look at the spectrum of genetic complexity, they’re really pretty simple meaning that they have one to half a dozen mutations.

Now mutations aren’t the whole story, but it’s a good starting point and if you only have maybe 10, 15 genes that are currently mutated in a disease, it’s trackable. You can figure this out. You can figure out what they’re doing to allow them to win and once you know that, you start figuring out how to beat them back. And so, I think that their time is gonna come. I don’t know if it’s this year as I said, but I think it’s definitely doable.

You know, CML, when I was a kid, when I was in medical school my parents had a good friend with CML who died with CML. Now, it just wouldn’t have happened. He would have been fine, but he was on, for a long time, ineffective therapy, transformed to an acute leukemia as they all did, and then it becomes really untreatable. And now we have these magical drugs, semi-magical drugs, that for the vast majority of people just – it’s a pill a day. It’s amazing.

Well, you’ve got that work on your whiteboard and in the lab and your colleagues around the world and you had told me before the program started that you all are collaborating better now than ever before. So, Dr. Joseph Scandura from Weill Cornell in New York City, thanks for what you do as a physician-scientist and thanks for spending time with us today.

Dr. Scandura:
It was my pleasure and thanks for helping patients through what is a difficult ordeal I think in terms of adjusting to a diagnosis and getting information.

Well, thank you for joining us and Weill Cornell folks have been great and send our best to Dr. Silver too. He’s in his 90s and still going strong.

Dr. Scandura:
Yeah, he’s traveling today.

Thank you so much for being with us for this Patient Empower Network program. Thanks to Incyte for helping fund our series. We appreciate their commitment to the MPN community and as always, I just sign off by saying I’m Andrew Schorr and remember, knowledge can be the best medicine of all.

Ask the MPN Expert – Dr. Naveen Pemmaraju

Ask the MPN Expert – Dr. Pemmaraju

“Ask the Expert” session with MPN specialist Dr. Naveen Pemmaraju from The University of Texas MD Anderson Cancer Center.


Andrew: And greetings from near San Diego, Carlsbad, California. I’m Andrew Schorr from Patient Power. Welcome to this patient empowerment network program, and thanks to Incyte Corporation for helping make it possible. They have no editorial control. I’m a myelofibrosis patient, have been for several years, so I’m vitally interested in this. Welcome to our MPN community, and welcome to one of our favorite experts joining us from MD Anderson Cancer Center in Houston. There’s Dr. Naveen Pemmaraju. You can see behind his desk there all the working on the cures of tomorrow, but Naveen, thank you so much for being with us.

Dr. Pemmaraju: Thanks for having me, Andrew. My pleasure.

Andrew: Okay. Let’s get right started. We’ve gotten all sorts of questions in. If you have a question, send it to MPN@patientpower.info, but we’ve gotten a lot already and I’ll start to buzz through them over the next 30 minutes. This question is from Cynthia and she says, “I was diagnosed with ET (Essential Thrombocythemia). I’m JAK2 positive,” so she has that JAK gene. “When I was 66 years old,” now she’s 68, I’m about to be 68 as well, “What markers on my blood work, asides platelets, are important for my doctor to watch? What indicates a need for another bone marrow biopsy?”

Dr. Pemmaraju: Well, thanks, Andrew. And thanks to the question from Cynthia out there. This is very important. This is what we talk about day-to-day, week-to-week in the clinic. There are a couple of perimeters outside of the platelets. One, I would say the most important for us to watch are the other of the big two. That’s your hemoglobin number, also known as anemia; if it’s too low, or polycythemia, if it’s too high, and then the white blood cell count is also very important. Again, if too high, or too low, it can tell us what’s going on.

With ET, the key thing is it can transform, or change into any of the other MPNs. For example, PV (polycythemia Vera), myelofibrosis, or – and I hate to mention it, but it does happen five, maybe seven percent of our patients, where the disease can go to Acute Myeloid Leukemia, AML. So, distinct blood count changes, either too high, or too low, can give us clues if the MPN is changing, or in fact, going to AML.

And so, the answer for a repeat bone marrow is based on that, which is, let’s look together, patient and provider to see if there are subtle or avert changes in the blood counts that are markedly different from the previous visit, rather than having a pre-prescribed, every three months, or every six months type of a deal.
Andrew: But, Naveen, with all you’re doing now with sophisticated testing, do you still have to poke us in the hip, or couldn’t they just do it from our arm?

Dr. Pemmaraju: I wish, Andrew. I think this is very important. I think with the juxtaposition, you have this sophisticated gene panel testing, JAK2 CALR, MPL, and yet we’re still sticking a needle in people’s backs in a very painful procedure. Nothing still has overmatched as the gold standard, the bone marrow aspiration biopsy. So, for now, we’re – pun intended, I guess – stuck with this procedure. But your point is a good one. For example, with bone marrow transplant, can you believe it nowadays, they’ve moved from not having to exclusively do it from bone marrow source to peripheral blood, so I think you’re on the right track and we need to work on different ways of accessing this important information.

Andrew: Okay. One thing about bone marrow biopsy, it doesn’t have to be painful. It’s uncomfortable, but it doesn’t have to be painful if you have somebody experienced doing it.

Dr. Pemmaraju: I wanna emphasize how right that is because at least here, at our center at MD Anderson, as you know, we have a team that is dedicated to doing it many, many people, many repetitions doing it, so there might be local discomfort, but a lot of our patients do not experience pain. I’m glad you brought that up.

Andrew: Right. And that’s been my experience both there, and at other major centers. Okay. Here’s a question from Denise. Denise says, “I have PV and I’m trying to improve my health by making smoothies containing large amounts of dark green vegetables, such as spinach, kale, and watercress. I’ve been warned by some members of our community that these foods will increase iron and raise the hematocrit, putting me at risk. Is that true? And should people with PV avoid these foods that are high in vitamin K?”

Dr. Pemmaraju: Well, this is an important question and I remember five to 10 years ago we would say things like, “Well, we don’t really know the answer,” or you know, “Diet doesn’t really have anything to do.” But now with more and more understanding of the total therapy for patients and approach to the whole body, I think this is an important question. So, yes, iron levels do matter. Too low, then you’re iron deficient. (That can definitely happen in our patients.) Too high, potentially may fuel the fire, if you will, for polycythemia Vera.

So, I think iron levels are important to watch and certainly can be increased by what our question is being asked about. But there’s another aspect, too, that some of the medications that we prescribe and take. One example is Coumadin, or Warfarin that a lot of our patients know, which is a high-level blood thinner. It’s an anticoagulant. And man, oh, man, that is exquisitely dependent on the vitamin K pathway. So sensitive, that in some patients in some cases even salad consumption, or spinach, so healthy foods because of the vitamin K level in them can alter this level. It’s called the INR. And so, it’s something we have to watch out for.

So, not only in terms of iron metabolites, but also drug-to-drug interactions. So, it is always best to mention these things when we’re going on new medications.

Andrew: Right. Talk to your doctor.

Dr. Pemmaraju: Talk to your doctor.

Andrew: What you’re doing –

Dr. Pemmaraju: Everything.

Andrew: – what you’re eating. Yeah. Okay. Here’s a question from Sally. Sally says, “I have ET with the MPL mutation. So, I have JAK, but there’s also MPL. I believe, not much is know about my mutation. Can you shed light on it, or me and our community here today?”

Dr. Pemmaraju: Yeah, great question. So, when I look at these mutations as the big three, I go back to the time of William Dameshek, who hypothesized in the ‘50s and ‘60s that MPNs would be a unified group of diseases; ET, PV, and MF. And now, 67 years later, we’ve proven that. So, JAK2, we’ve known about since 2005. The most common, most major recurring mutation, fifty to 60 percent of patients of myelofibrosis. Then in 2013, 2014 the CALR mutation was elucidated. Can you believe, that’s only been four, five years. That’s the second most common. But there’s a third of the big three. That’s the least common, the MPL; MPL mutation.

That’s a mutation in something called the thrombopoietin receptor (TPO), which is in charge of helping to stimulate and make platelets. So, in terms of MPN patients, it does make sense and it has something to do with platelets, and that axis. It is the least common; by far the less common of these three, so I would say maybe something to the point of three to seven percent of our patients will have it.
Up until recently, we didn’t know if it had any prognostic significance, but our Italian colleagues published a very nice paper in Blood a few years ago, independent of the IPSS risk, that I’m sure we’ll talk about later. That if you just take patients with myelofibrosis, not ET and PV, you can stratify our patients based on the mutation risk. And not everyone knows about this.

For example, in this scoring, CALR mutation alone is the best prognosis for our patients. JAK2, or MPL is what’s called an intermediate prognosis, and the so-called triple negative, if you don’t have any of these big three, the implication being that you likely have something else, like ASXL1, then those patients tend to have the worst prognosis. So, MPL helps us to diagnose and confirm an MF diagnosis, and it also may have prognostic significance in our modern era.

Andrew: Okay. I don’t want people to freak out because this is a moving target as they learn and say, “Oh, my god. I have triple negative…

Dr. Pemmaraju: That’s right.

Andrew: Right. Okay? Because there’s progress going on all the time.

Dr. Pemmaraju: Well said.

Andrew: This is what they’re learning now. Okay. Now. Here’s the big one and you mentioned it. You said, a small percentage of us with myelofibrosis have the risk of progressing to AML. I know there been a lot of new drugs now either approved, or in development for AML. And some that help people who have secondary AML.

Dr. Pemmaraju: Oh, yes.

Andrew: Right? But tell us about the risk of progression, and then what do you do about it?

Dr. Pemmaraju: Right. So, that’s a great topic, and as you know, you’ve been doing this for so long now. This has often been a very not great part of the conversation, but it’s an exciting time for our patients based on the research I’m about to share. So, the first part is progression to AML, which we touched on earlier. We do have an objective prognostics scoring system. Actually we have so many scoring systems now that many of our patients are starting to see them.

But the IPSS, or International Prognostics Scoring System, was first developed by our colleague, Cervantes et al, this is right before 2010, so ’07 to ’09. That one is supposed to be applied at diagnosis and based on five of these risk factors, we can prognosticate, or tell which of our patients are at a higher risk for AML. And so, a lot of our viewers ask that. So, it is true. Age – over a certain age, white count of 25,000, circulating blasts, constitutional symptoms, and anemia made up that original five.

Since that time, there are dynamic scoring systems, DIPSS, DIPSS+ and others that include, or modify as some of those risk factors. So, we can tell, at least based on a textbook impression, who has a higher likelihood of going to AML. Once our patients go to AML, there’s a lot of hope now. There have been four – count them – four new FDA approvals for AML in just the last 12-24 months. They apply to different segments of AMLs, two of them are targeted therapy, so one drug called Midostaurin hits the FLT3 inhibitor, one drug hits the IDH1 and 2. Actually those are two separate drugs.

The drug you were referring to had a code name CPX-351, or VYXEOS, and it does have an approved label for so-called secondary, or therapy-related AML. Although I will caution our viewers that – MPN patients, specifically, we’re not included in those early data sets. They were more geared towards patients with MDS leading to AML, but the principle is there for us.

And then finally there’s another drug called Gemtuzumab or Mylotarg. So, you have four FDA approvals, ongoing clinical trials with combination therapy, excitement and ongoing investigation for CAR-T cells, optimizing stem cell transplant, and then combining possibly MPN drugs with AML drugs in a clinical trial setting. So, I think this is actually a very, very important time to talk about AML in all of our MF and MPN sessions.

Andrew: Okay. Just one brief question, and – if someone like me, where I’m on Jakafi myself, but if that sort of poops out, or that, or another medicine is not working for me, and I’m developing AML, do you feel now it’s a more hopeful time than it’d had been previously?

Dr. Pemmaraju: I do, Andrew, and you know me. I used the word ‘hope’ very seriously and very carefully. Before with AML – and I mean, just five to seven years ago, it was not as hopeful of a time for us, as researchers, and for our patients. Not just because of the FDA approvals. That obviously is very encouraging and applies to a lot of our patients, but also because of the funding, the research, and the ideas for combination chemotherapies, and the emergence of these immune therapies. I think it’s a hopeful time for all of us involved with AML.

And specifically as you were mentioning this secondary, or post-MPN, or post-MDS AML, which is largely been an urgent unmet medical need.

Andrew: Okay. And just to everybody understands, AML, Acute Myeloid Leukemia, so it’s acute and as has been in the past a five alarm fire and now they’re developing medicines for that. All right. Let’s go on. Bonnie has a question. “I have myelofibrosis and my only symptom is that my spleen is enlarged. I’m on Hydroxyurea, but hesitant to switch to Jakafi or Ruxolitinib. Assuming no real discomfort and just moderate weight loss and stable blood counts, does an enlarging spleen itself cause problems?” And also, I guess the bigger question, Naveen is, is there a penalty for waiting if there is a treatment that might line up with what you got?

Dr. Pemmaraju: You’re right on. Yeah. This is very, very serious, important topic. So, for the first part of the question, the spleen itself being enlarged can in fact cause some really, really big problems for a lot of our patients. It is true, as the questioner’s asking, that one can have mild splenomegaly. So, a spleen that’s slightly enlarged, not yet causing physical symptoms of early satiety, which means getting full fast, or physical discomfort, but a lot of patients do have that. So, yes, a big spleen alone can cause not only local problems, but also systemic. Because again, it’s a disease of cytokines; messengers and proteins that are being scattered all throughout the body, causing the body to feel flu-like symptoms, or fatigue.

Now, the studies for Ruxolitinib are very specific. These are two Phase 3 studies, they are called Comfort 1 and 2, published in the New England Journal five six years ago now. And they did include patients with intermediate to, or high-risk disease. Or intermediate to high-risk disease, shall we say. And although the spleen itself doesn’t come out in the scoring system, some position is that it should be patients with more advanced, or higher scoring diseases than say someone with lower risk disease.

So, with the trial data that we have we know a couple of things. 1) The drug got approved in those more advanced patients. 2) There was early crossover that was allowed. So, one of the comfort studies, Andrew, was as you know, randomize to placebo. So, no active therapy, and one was best available therapy. Even with the early crossover allowed to the Ruxolitinib, both are not showing overall survival benefit. Translated into more layman’s terms, what that means is, it does appear, maybe, possibly, that if you got the drug at the beginning early on, there looks to have been some long-term benefit.

We won’t know that until further studies are done, and those studies are being planned. Those are called ‘early intervention’ studies, so people at a lower, earlier stage, low risk, Intermediate 1, and I think we’ll all be eager to see how that benefits our patients.

Andrew: Okay. Great. So, the penalty for waiting – right now it appears there could be a penalty. In other words, it could be better to get on it. Don’t wait. If you and your doctor agree, there’s a therapy for you.

Dr. Pemmaraju: I think that’s exactly the resource position to take, which is I think that – I believe that there are a subset of our patients who exactly fit what you said. They are symptomatic, out of proportion to the risk scores that are available. The spleen is highly enlarged, although they have lower intermediate risk by IPSS. And that’s exactly the are of investigation for myself, and our colleagues. And even in the clinic there might be some role to assessing patients as you said like that. So, it shows you the limitation of these text book scoring systems and how much research we have left to do.

Andrew: Okay. Well, you know more than you did before, so, I –

Dr. Pemmaraju: Well said.

Andrew: – I’m happy about that. Okay. So, here’s a question from Jane. She says, “I have myelofibrosis, but it’s not progressing, and I’m CALR negative.” So, that’s one. “I’m JAK negative.” That’s two. “And I’m waiting to hear if I’m actually triple negative, as you said, which would be JAK, CALR, and MPL. Are there medicines to slow progression for me?”

Dr. Pemmaraju: Well, that’s the ultimate question. Isn’t it? So, the first concept is this triple negative. And if our viewers have heard that before you have, that was borrowed from the breast cancer literature, which was a similar sentiment, which is having the top three markers negative. And just in that case, as in RMF, the supposition is the same, that that means that you have a higher risk disease.

But going from negative to positive, what it does mean now with the new sequencing and molecular studies that are coming out, is that it really looks like 90 percent, maybe even close to a 100 percent of patients, have some form of a molecular driver. And those other mutations you’re going to start to hear about are becoming common; ASXL1, TP53, EZH2, IDH, etc. etc. So, triple negative may mean that we don’t have those big three, but there might be something else that’s driving the MF, and it means that it’s a higher risk to progress to AML and for some patients to not do as well.

But this questioner brings up a very good point. What the textbook risk score says does not have to imply to each individual patients. So, just because the finding is that, okay. Triple negative patients as a population may do worse, it may not apply to that individual patient. So, in this person’s case, maybe they’ve been diagnosed very, very early. That’s a good thing. Maybe the driver mutations and the triple negative matter, which is what I think. So, ASXL1 mutation vs. some other ones.

And then finally, each patient is different. Everyone’s case is different. You have other co-morbidities, other underlying drivers of disease. So, I think that’s the good point. But, we do have to say, at least for right now, I like your phrase ‘of a moving target’. The understanding that if you are this triple negative disease in this classical sense, should mean that you are a higher risk at some point to progress, as compared to others in your group, and so, possibly closer monitoring and observation is necessary.

Andrew: Right. And see an MPN specialist. Because what if there’s a drug in development that’s an AS – What is it? AS –

Dr. Pemmaraju: ASXL1.

Andrew: Inhibitor. And that’s driving your bus. Right? Maybe you wanna be in that trial. [

Dr. Pemmaraju: Absolutely right. Clinical trials are important for all of our patients with any rare cancers, or any cancers in general.

Andrew: Right. Okay. Let’s go on. I just wanna take this question from Susan. It really rang true for me. Susan writes, “Is it common for an ET patient to experience numbness in the scalp, ears, and face? I’m currently on 1,500 milligrams of Hydrea daily.” And I wonder if you can broad this out because I was telling you before the program, I’m getting every once in a while – I wake up with a little prickliness. Not itchy, and I go back to sleep, but is that related to my MPN? So, she has scalp questions, is it the MPN, ET whatever? Is it the medicine?

Andrew: This is coming up in my clinic on a weekly basis. The short answer is, yes. It’s always due to the MPN. And I’m here to tell you why. This is an underappreciated part of what we do as healthcare providers in patients. For anyone who’s ever filled out the Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score:, developed by Ruben Mesa, his colleagues, now shortened down to a nice, nifty 10 ques – sheet. You know, actually, peripheral neuropathy is one of those 10 questions. Do you have numbness and tingling? So, even though we don’t talk about it, that’s our fault, peripheral neuropathy is a thing. It’s a common aspect of the MPN.

No. 2 is – and you brought this up to me nicely as well, is some of the mediations that we prescribe at the chemotherapeutic level can also cause nerve damage and neuropathy. JAK inhibitors either as a class, or some of these individual ones, both FDA approved in clinical trials have been associated with either a central, or peripheral neuropathy. So, I think that’s another big aspect.

And then finally, I hate to say it, but these drug-to-drug interactions of all of these medicines can cause that. When you factor that, plus vitamin deficiencies, thyroid deficiencies, iron abnormalities, restless leg syndrome, our patients have a host of reasons to have neuropathy. Usually this is an intermittent phenomenon, a come and go phenomenon. When it starts to become more of a permanent phenomenon and progressive, that’s a big concern, and that would really require a separate neurologic work up.

True, there are some chemotherapy drugs that can cause that, but I would say that would necessitate a multi-disciplinary approach; neurologists and all of this kind of thing.

Andrew: Okay. You used the name of a drug that people take. Is a blood thinner, Coumadin. Somebody may take diabetes medicines, I also have Chronic Lymphocytic Leukemia and take medicines for that. Okay. So, if we’re developing some of this and we have an MPN, which of the many doctors we have doo we go to first – do we go to you as our MPN specialist? Do we start there?

Dr. Pemmaraju: Yes. Absolutely. I think the phrase and the motto of every MPN expert that you’ll meet (and you and I know all of them now) is, ‘Tell us everything.’ Because I will tell you what. Now that we have more understanding – not full understanding yet, but more understanding of the biology of these diseases, it turns out that a lot of things that are happening are due to MPN.

One example I’ll give you, Andrew, our colleague and friend, Claire Harrison has pioneered this phrase called, ‘presenteeism’. Presenteeism. Not absenteeism, as we learned when we were younger. The concept that our patients with MPN are there, they’re here at work, with their loved ones, they’re at dinner, but they’re not really there. That’s also a question on the questionnaire; inability to concentrate. Subtle, subtle, subtle, but this is part of the MPN process. We’re not talking about it enough, but programs like this will get the message out there. So, tell your MPN doctor everything because more than likely they know it’s part of the MPN.

Andrew: I gotta tell my wife. I’ve been married 33 years.

Dr. Pemmaraju: This is all recorded, so you can tell her.

Andrew: All right. Esther, where are you? Okay. No. Let’s go on. So, Heather sent in this question. “My local hematologist, oncologist will only give me a phlebotomy after my hematocrit is over 51. What is the standard marker? I have PV and I’m really struggling with symptoms.”

Dr. Pemmaraju: I actually have data to share with you and your viewers. So, before four years ago, we did use to do it either based on convention, symptom burden, or a pre-designed abstract number. But now we have data. So, our Italian colleagues, Barbui and colleagues published in the New England Journal about four years ago a very nice paper that starts to answer this question. They randomize patients with P. Vera to two groups. They called it a liberal group, where you could get phlebotomies at any number essentially just like what’s being asked here, and then a more stringent group, which they came up with the hematocrit goal of 45 and below. Or below 45.

And the trial was actually stopped early because it showed a four-fold decrease in cardiovascular morbidity and mortality. That means, four times less chance of people having cardiac events or cardiac deaths in the stringent phlebotomy group. That is when you put the goal below 45. Yes, it’s only one study, but it’s with several hundred patients with P. Vera in a nice controlled situation. So, that has become a lot of us – for us, the de facto of standard of care.
So, I would advise, if you’re a higher risk patient with P. Vera, the so-called triple therapy approach, where you’re doing, you know, baby aspirin if you qualify. The phlebotomy goal of 45 and below, and then of course, cytoreductive therapy if you need it in the higher-risk situation. So, 45 and below, it should be validated, we should do more studies here in the States, but that’s something that I think we can use with high-level data.

Andrew: Okay, thanks. Here’s a question we got in from Kimberley. She says, “My daughter is 22, she was diagnosed in 2013 with ET, and she’s been on Hydroxyurea, but is decided she no longer wants to take the med. What should she be aware of, or cautious about, given that she’s no longer taking it?”

Dr. Pemmaraju: Ugh. Well, this is an area that’s very dear to me and very important to my research. With our group here, with Dr. Serge Verstovsek and my colleagues, we just published a paper on our experience with adolescents and young adults with MPN, or AYA. As its own separate field, AYA cancer has become a very important understanding that really didn’t exist, in my opinion, 20 years ago. But our patients are not always older patients. So, young patients can get MPN, too. Yes, patients in their teens and twenties can get them just like this questioner.

So, this is a type of patient that I’m seeing quite commonly in the clinic. Couple of points to say. One is, who can blame her? Who wants to take a life-long, indefinite oral chemotherapy that may or may not have short-term and long-term side effects? In our study what we found is, approximately 10 percent of our patients met this definition. The NCCN gives it, I think, age 16 to 39. So, younger than 40. And out of those patients, I was surprised to see that a good seven percent had a thrombotic event. That means a blood clot, either at the time of diagnosis just prior to, or just after. Well, that’s a pretty good clip, and that would be more than the general population than what you would expect.

The problem with the young patient with MPN has several issues. One is, what about at the time of fertility and pregnancy? Two, what about at the time of surgical procedures? I’m talking about routine things, such as dental and other care. And then three, as they start to transition into their older adult years. So, in this patient’s case, this is a very difficult thing. We don’t have many drugs. We have Hydroxyurea, we have Interferon, which possibly might be better for a younger patient. If someone has myelofibrosis, there’s no age requirements. So, if you qualify, then the JAK inhibitor, as a class.

But this is just one of those in-between, vulnerable populations, and we really don’t have great treatments for in general, an AYA cancer, and specifically here. And so, the main thing that we would say to this person is, really, really close follow-up early on with an MPN expert, as you always advocate. Two, is at the time of fertility planning, pregnancy in our family planning is to have high-risk maternal-fetal experts involved early on. (I think, this is something important.) And three, really cautious planning in and around surgical procedures, looking for bleeding and blood clots. I think those are some basic guidelines for anyone to follow.

Andrew: Well, great advice for mom and daughter. I wanted to post this, just a quick question from Caroline who lives in the United Kingdom is diagnosed with primary myelofibrosis four years ago at age 49. And she said, “I’ve tried to find others with myelofibrosis of a similar age, but so far no luck.” So, is being diagnosed at her age, age 49 with myelofibrosis, unusual?

Dr. Pemmaraju: There you go. That’s perfect. So, that also goes along with our “Young people get MNPs as well.” This was a disease – first of all a disease, now we recognize it as a cancer that was thought to be 60, 70, 80, 90 and older. And now we realize that there’s a significant subset of our populations diagnosed in their teens, twenties, thirties, and forties. So, we definitely want our question – our viewer to know, no, you’re not alone at all. Please, see our paper that we just put out there and several other of my colleagues, including Brady Stein and others.

Two is, my goodness. Not only you’re not alone, but I actually believe – and I know you know this too – that a lot of rare cancers are sometimes are under diagnosed and underappreciated. It does require expert bone marrow, expertise, someone to identify it, someone to do a bone marrow. And lastly, for this patient looking for other patients, I would refer them to sources, such as this one. Patient Power, support groups on Facebook, we have a Twitter feed, as you know, a grassroots Twitter, that’s investigators initiative called #MPNSM (myeloproliferative neoplasm on social media).

So, there are lots of different ways for this person to connect with not only younger patients with the disease, but also as a support group, virtually. And I think platforms, such as Patient Power, have frankly revolutionized the way people have obtained information, have communicated with each other, and specifically for a patient like this in the UK, who is not able to connect with me. And when there are people all over the world waiting to talk to her.

Andrew: Right. I wanna call at our friends in the United Kingdom, MPN Voice.

Dr. Pemmaraju: Oh, yes.

Andrew: It’s Claire Harrison, who you mentioned, wonderful, devoted.

Dr. Pemmaraju: Outstanding.

Andrew: She’s an expert, out of London, helps run it. So, please, connect with them. Okay, here is a question from Erin, as we’re getting near the end of our program. “Can ET ever cause systemic inflammation? And is that what causes symptoms? The inflammation.”

Dr. Pemmaraju: Yes, yes, and yes. So, inflammation, I think, used to be a word that may have been potentially, if I may say, a wastebasket term, but now is a very specific term. So, now we know that a lot of our hematologic disorders and malignancies lead to a high level of inflammation. That means tissue damage. Tissue injury. That’s what inflammation means. There are some conditions that the patient does not even have a blood cancer diagnosis, but has a molecular mutation, that’s called CHIP (clonal hematopoiesis of indeterminate potential), and those patients appear to have a higher likelihood of cardiovascular disease and death. That’s New England Journal of Medicine. The likely pathway is inflammation.

In our patients with MPN, even the quote on quote, earlier stages, such as ET and PV. This is a disease of cytokines and inflammation. So, high levels of abnormal messengers and signals. So, yes, inflammation is part of the disease, patients have a higher rate of cardiovascular events and death. That’s inflammation. And then of course, the bone marrow milieu itself, as it progresses to myelofibrosis has an up ramp, if you will, of cytokines and inflammation. Last part of it is the therapies that we’re working on are trying to either target inflammation itself, or to bring down that level.

Andrew: Okay. I wanna see if – Here’s a – one that just popped in as we get near the end of our program. Roger says, “Are there any drugs being studied that improve anemia in patients with a low hemoglobin?” What’s the easiest way to find out about clinical trials if you live out of the state, or out of the country where this trial may be –?

Dr. Pemmaraju: Yes. Your best resource to look that up is run by the Federal Government, the NH, it’s called clinicaltrials.gov, that’s dot G-O-V. This is an outstanding website, well curated, updated as quickly as they can, and it has a nice search function. You can search by investigator, disease type, condition, and there’s even a box for ‘other’ where you can type in something like ‘myelofibrosis’.

There are several drugs in development. These drugs are known as Luspatercept and Sotatercept, for example. And they’re a class of drugs that are anemia targeting in myelofibrosis and myelodisplastic syndrome. So, the answer is, yes. And you can find out these types of clinical trials either online at this website, or at other websites. But this is an important, urgent, unmet medical need that we are working on, and there are active clinical trials for patients to enroll on.

Andrew: Well, okay. And the last thing I would ask you about – and this always comes up, Naveen, but I wanna hear what you have to say is somebody we have people with ET, we have people with PD, MF, and we talked at one end about acute myeloid leukemia. What do we know about progression now? So, if I’m sitting there with ET, am I necessarily going to go onto PV, or MF? Or anywhere along the line, and how do we know?

Dr. Pemmaraju: We do know a little bit more. So, the answer is no. So, a lot of our patients do stay in the chronic phase, as you’re asking. So, if you’re ET, or PV – and our European colleagues have really done these nice population studies, where the majority – the vast majority of patients with ET and PV are expected in the modern era to have normal life expectancies as long as you’re mitigating in some bleeds, clots, and these type of events.

But for the minority, who don’t have a normal life expectancy, you’re talking about progression to AML, which is a minority of all these. Right? Maybe 5-7 percent of cases at the most. There are some things we have identified. One is that there are some dynamic acquisition of molecular mutations that are happening at the time of progression. And what I mean by that is, there are new injuries to the DNA that people appear to be picking up. So, two important studies our colleague, Raajit Rampal showed that the acquisition of TP53 mutation, which is the guardian of the genome present in 50 (five, zero) percent of human cancers. That looks like it’s more common when ET and PV are trying to take off to AML.

Another study by our Mayo colleagues just published in Blood Advances showed that other mutations, such as PTPN11, or RUNX1, just to name some particular ones, and then we’ve known about ASXL-1 now for a while. So, rapidly change in blood counts in concert with new molecular mutations, and then a baseline if you have high-risk mutations. That seems to be a way for us to predict who might transform faster than others.

Now, that’s an addition to the traditional risk factors that you and I have already discussed, the IPSS risk, or etc. So, there are some ways that we can monitor. A lot of these may be in the research setting. Some are ready for the clinic, but there are some ways now.

Andrew: Okay. So, ladies and gentlemen, I hope this program is been worthwhile for you. Remember that the big meeting of Dr. Pemmaraju and his colleagues from around the world with thousands of hematologists is this the American Society of Hematology meeting, which once again, will be, yay, near me, in San Diego.

Dr. Pemmaraju: Very good.

Andrew: Esther and I’ll just drive over. And the Patient Power team will be there, the Patient Empowerment Network team will be there. So, we’re there for you. So, look for more programs as we go through the fall, and certainly in December, when this meeting happens. And that’s where a lot of the research that Dr. Pemmaraju talks about is presented.

Dr. Pemmaraju: Right.

Andrew: And then we’ll have more news. So, we’re living with these long-term conditions, thank god for most all of us, and it’s a moving target, as I’ve described. I wanna thank you for joining the Patient Empowerment Network program, for sponsoring this program. We thank Incyte Corporation for its support, and Dr. Naveen Pemmaraju from M.D. Anderson, and the Leukemia Department there, thank you for being a partner in this, and just explaining things, and your passion. And Naveen, again, back to your whiteboard back there. Figure it out.

Dr. Pemmaraju: It’s all there. Yes, sir, Andrew.

Andrew: It’s all there. Figure it out. Okay? All right. Thank you so much for being with us from around the world. We love it. We’ve got a community. This is what it’s all about and we’ll have future ask the expert programs. I’m Andrew Schorr near San Diego. Thanks to the Patient Empowerment Network for making all this happen. Remember, knowledge can be the best medicine of all.

MPN Patient Cafe® October 2017 – Tips for Managing Life After Diagnosis

MPN Patient Cafe® – Taking Back Control – Tips for Managing Life After Diagnosis from Patient Empowerment Network on Vimeo.

A panel of MPN patients and care partners discuss taking back control and share their tips for managing their new normal after diagnosis.

MPN Patient Cafe® July 2017 – Finding Trustworthy Information

Patient Cafe® MPN – July 2017 from Patient Empowerment Network on Vimeo.

Carol Preston is join by MPN patient, Andrea, and her care partner, Denise in this session of the Patient Cafe®. They discuss where MPN patients and their care partners can go to find trustworthy information.

Living Well with MPNs – What You Should Know About Genetic Mutations

What You Should Know About Genetic Mutations

Living Well With MPNs: What You Should Know About Genetic Mutations from Patient Empowerment Network on Vimeo.

Should you get a genetic test? JAK2, MPL, CALR, ASXL1: Mutations associated with myeloproliferative neoplasms (MPNs) can bring up lots of questions. What do they mean, and how do they impact your disease? The goal of this webinar, featuring Dr. Alison Moliterno from Johns Hopkins School of Medicine and Dr. Stephen Oh from Washington University School of Medicine, is to help patients understand genetic mutations.


Andrew Schorr: Hello and welcome to this Patient Empowerment Network program, produced by Patient Power. I’m Andrew Schorr joining you from Carlsbad, California. Over the next hour we’re going to talk about something that’s very personal to me and probably to you, and that is the whole idea of genetics related to living with an MPN. What does it mean? Does it change over time? What is your version of an MPN? What does it mean for prognosis? What does it mean for treatment? What does it mean for clinical trials opportunities? So we’re going to be discussing all of that.

I want to thank our sponsor, Incyte Corporation for supporting this educational activity. We’re going to cover the country and we invite your questions as we go along. Send them to MPN@patientpower.info. Many of you have. And remember if you have to bow out at some point, the replay will be available and we’ll have video clips. So we’ll reach literally a few thousand people living with MPN worldwide, and we’re happy to do that.

Let’s get started. First I want to introduce you to one of our medical experts who’s joining us. He’s been on programs before. He joins us from Washington University and the Siteman Cancer Center in St. Louis; that’s Dr. Stephen Oh, who is an MPN expert there. Dr. Oh, thank you so much for joining us.

Dr. Stephen Oh: Hi, Andrew. Thanks for having me.

Andrew Schorr: Thank you, Stephen. Okay, let’s go from St. Louis to Baltimore, Maryland and the Johns Hopkins University Medical Center and another expert in MPNs who’s been with us before, and that is Dr. Alison Moliterno. Dr. Moliterno, thank you so much for being with us today.

Dr. Alison Moliterno: Thank you, Andrew. Thank you for having me.

Andrew Schorr: Sure, pleasure. We’ve got a lot to cover. And then also I want to welcome back one of the members of our community, someone who was diagnosed many years ago, a couple of decades ago with ET, and then a year ago it became myelofibrosis. She’s a preschool teacher in Peoria, Illinois. She’s been with us on our programs before; Marsha Krone. Marsha, thank you for being with us once again.

Marsha: Thank you. Hi, Andrew.

Andrew Schorr: Marsha, let’s visit for a minute. I was diagnosed in 2011 and then eventually had a genetic test which came up with a bunch of results. One of them for me, if I get it right, JAK2V617F.

I had no idea what that was, and then a couple of other genes that to me seemed kind of like alphabet soup. And I had one of the peers of these experts here, Katrina Jamison. We went over it and she said I think it’s the JAK that’s kind of driving things. We’re going to talk about what are the driver genes, and what may not be, or what do we know at this point. Marsha, you had a genetic test, too. What did it say?

Marsha: My genetic test came out as Calreticulin type 2.

Andrew Schorr: Okay, so we’re going to figure out what that means. Dr. Oh, let’s start this way. People think genetics. I know genetics maybe had something to do with being bald, and I see you have a similar hairline; or dark hair, or brown eyes, or whatever. Hereditary genes; are we talking about that or are we talking about something different?

Dr. Stephen Oh: That’s a basic question that comes up with almost every new patient that I see.

The short answer is that when we’re talking about genetics with relation to the MPNs, we’re not talking about those kind of things that you’re born with that may affect your hairline and whatnot. These are genetic mutations that are acquired over time that you’re not born with; they’re not passed down to your children or your relatives, etc. So that is a very important distinction that I try to make clear with every new patient that I see.

Andrew Schorr: Okay, and one follow up question to you. People say okay, Doc, what gave me this genetic injury, if you will, to lead to these illnesses? Do we know?

Dr. Stephen Oh: That’s another question I cover with almost every new patient; that I think for that one I guess the answer is a little less satisfying. My answer is that for the most part it’s random chance.

What I mean by that is that we know particularly from research that’s come out n the last five or so years that all of us acquire mutations randomly over time as we age. But fortunately for most individuals, those mutations land in spots where they really have little to no consequence. But for those that, for instance, acquire the JAK2V617F mutation or acquire a Calreticulin mutation, that really becomes most likely the main driver for what ultimately becomes an MPN.

Patients of course ask did I do something wrong, was I exposed to something? And while we can’t necessarily exclude that those are factors, I think for the most part it’s that just kind of randomly these mutations landed in the wrong place.

Andrew Schorr: Dr. Moliterno, we’ve mentioned a couple of these onco genes I think you call them – cancer genes, the JAK2 gene and Calreticulin type 2, I didn’t even know about that.

Can you first of all rattle off some of them just so we know the landscape of what are genes that seem to be associated with MPNs today, knowing that this will probably expand?

Dr. Alison Moliterno: I always like to tell patients a little bit about the history when these were first diagnosed because we talk about them now as if they’re common knowledge, but they are really quite recent in our understanding. We’ve known about the myeloproliferative diseases for more than 100 years, but it wasn’t until 2005 until the driver of many of the diseases was understood to be JAK2V617F. So that discovery occurred in 2005. Before the JAK2 discovery, we didn’t understand really if it was acquired mutations and what genes were involved. JAK2 is the most common of these.

If you look at 100 patients with the classical MPN, meaning PD, ET, and myelofibrosis, 75 percent overall of those individuals will have the JAK2V617F mutation. Not long after the JAK2V617F mutation there was a discovery in mutations in M-P-L or MPL. That accounts for about 5 percent of those 100 individuals with either ET or myelofibrosis and then in 2013, that was the discovery of the calreticulin mutations that comprise about 20 percent of individuals who have ET or myelofibrosis. So 2013, that’s fairly recent and those are the three drivers.

I like to say that if you could put the same mutation, the JAK2V617F or Cal or MPL mutations that we see in our patients, if you could put those, say, in a mouse; they would drive a similar disease in the mouse so that you get polycythemia vera in a mouse if you make the mouse have the V617F mutation. That’s how we’ve kind of come to understand that they drive the disease. They may not drive all aspects of it but they drive the basic process.

Andrew Schorr: I know there’s another gene that people have seen too; ASXL1. What is that one?

Dr. Alison Moliterno: In addition to these drivers we’ve also discovered a lot of genes that seem to modify the MPN or associate with certain subtypes of MPN. So for instance I said usually JAK2 MPL or CALR can all drive platelet count high and give a disease like ET. Then what happens when patients develop myelofibrosis? We find that perhaps other lesions are acquired.

Those are genes that don’t drive myeloproliferation so much but they seem to drive the way that the chromatin or the nucleus is managed; they seem to maybe set up the other aspects of MPN that associate with myelofibrosis. And ASXL1 is probably the most common additional genetic lesion or acquired mutation that occurs in individuals with myelofibrosis.

Andrew Schorr: Okay. Dr. Oh, people may be tested and we’re going to talk about who should be tested and when. How do you know what’s the driver gene? And it sounds like this continuation of identifying genes just keeps going, too.

Dr. Stephen Oh:Certainly Dr. Moliterno gave a nice circle overview of when the three primary driver mutations were discovered.

We’re sort of lucky now that in today’s day and age we kind of look at this now as standard testing. So JAK2, MPL and calreticulin so much so that many physicians including myself, we kind of go about this in an algorithmic fashion. So for instance if I have a patient with newly diagnosed myelofibrosis, I’ll start by screening for the JAK2 mutation; if that’s negative, go to Calreticulin and if that’s negative go to MPL.

And so with those three genes, the majority of patients with any of the three main MPN subtypes, whether that’s QV, ET, or myelofibrosis; they’ll be positive for one of those three. There’s a subset that’s at least on the order of 10 to 15 percent of patients with ET and myelofibrosis who will be negative for all three of those mutations, what we’re now calling the triple negative category. But the vast majority of MPN patients will have one of these three mutations which we consider the main driver of mutations.

So, in some sense again we’re sort of fortunate that it’s become almost straightforward in terms of at least the top level genetic testing for these diseases.

Andrew Schorr: So that was my question to you, Dr. Moliterno. Some people have maybe had fights with their insurance company or their doctor as related to testing. How do you view this now and how could it be positioned on how it’s really not elected, if you will, but essential to get a clear picture of an individual patient’s situation?

Dr. Alison Moliterno: This comes up in my practice and I’m sure Dr. Oh’s practice all the time, in that in the olden days before our understanding of what causes these diseases, and again the cause was these acquired mutations and in the olden days we would use histology, looking under the microscope, looking at blood counts and sort of put a name to this polycythemia vera and myelofibrosis.

But within that was such a vast variability of what the disease actually was, that that name really did not tell us too much. Now, we’ve really come to understand that what you have is defined by these molecular lesions. They’re not just of academic interest; they actually really tell us quite a bit about what you’ve got, what your prognosis is, and where it’s going. So physicians, we really can’t function and counsel patients appropriately without this knowledge. So there’s no longer elective or of interest; it’s really critical in defining what you’ve got.

Andrew Schorr: Okay, everybody. You heard it, so this is what you’re advocating for with your MPN specialists, which hopefully you have like the two with us. This is standard operating procedure; there shouldn’t be nay question with an insurance company or anybody to help you and your doctor know what you’re dealing with

But then the next question is, Dr. Oh, where are we now even in research, where things are headed so there will be treatments that line up with the different genetic situation?

Dr. Stephen Oh: I’ll start my answer to that question by going back to when the field began to develop inhibitors of JAK2 for the treatment of patients with MPNs and extrapolating from other diseases, I think there was an assumption that the patients that would respond best or if at all to JAK2 inhibitors would be those that carry the JAK2V617F mutation. What we now know quite clearly is that even those patients that do not carry the JAK2 mutation, they also tend to respond to JAK2 inhibition. So again in the case of myelofibrosis, patients who are calreticulin mutants, they also respond to JAK2 inhibitors as well.

So that’s an example where I think in a good way the use of those kinds of treatments is not limited or defined or restricted mutational profile. But otherwise in terms of the research front, identifying or defining treatments specific to different mutations, we haven’t made a lot of headway there. For instance, you can imagine now we have identified the calreticulin mutation in many patients with MPNs; can we devise a treatment specific for that? So while again on the one hand like I mentioned, it’s a good thing that those patients do respond to JAK 2 inhibitors; can we come up with something very specific to calreticulin with the patients there?

There are certainly a number of research groups that are working on that kind of question, but we currently do not have anything specific in that regard.

Andrew Schorr: Dr. Moliterno, I want to get a question from you about that because I’m sure you’re asked. Somebody says well – Marsha could come to you and say well, I’m CALR so what do you have for me? And/or you also mentioned triple negative, and I think often I’ve heard that term in breast cancer; women who were triple negative there, and say what do you have for me in that situation? So talk to us a little bit about those situations, and does it vary now with treatment approaches yet?

Dr. Alison Moliterno: I think another aspect of this is we may not today have the specifically targeted treatment but as Dr. Oh mentioned, what we’ve learned is that these three main lesions, CALR, MPL, and JAK2 all seem to over signal or work their effects through this JAK pathway.

So even though you may not have the JAK2 mutation but you have the CALR, it seems like the end result of over signaling is in the same pathway and therefore JAK inhibitors would be beneficial in individuals who have that over signaling pathway. So that’s one thing we’ve taken away; that while even though we don’t have – and that’s a good thing because that tells us that inhibiting this pathway overall will benefit the majority of individuals with these lesions, whether they’re JAK2 or CALR or MPL.

The other thing about the profiling is how much of the mutation you have. So another I think we’ve learned is that we can measure the amount of these mutations, and that’s a variable across patients and gives us quite a bit of information about – again – the type of lesion, disease you have and gives us  better information about the prognosis and why you might have a little more fibrosis than someone else.

So again, the type of lesion you have and the amount; we’re now learning to use that information. I think another thing we’ve learned is these terms triple negative, which is a term that we understand okay, that means you don’t have any of the three drivers that we know of.

But as we’re learning more about extended mutation paneling or doing different tests to look at the entire genes, we’re finding that most of those individuals really do have lesions in the JAK2 gene, or the CALR gene or MPL that maybe aren’t in the specific areas that the test was sent for. So that’s another benefit of this revolution in being able to define these lesions personally so that your disease really can be diagnosed.

Andrew Schorr: Okay Marsha, you’ve been sitting there quietly and I wonder, is this making sense to you? You’re my co-host with this; is it making sense?

Marsha: It does make sense. When I first was diagnosed, they just said you simply have ET because you have it. Then they discovered more mutations. I like to know everything about how my body is working, so I wonder how valuable it is to have additional genetic testing to see if you have other mutations that may affect prognosis?

Andrew Schorr: Right. So Stephen, and also like serial testing at some other time? She went from ET to MF over many years, so when do you test again or how does this change?

Dr. Stephen Oh: Speaking sort of broadly at first, the more extensive genetic testing which is available through numerous laboratories now, which can test for any – quite often these panels went through 20 or 40 genes; some of them hundreds or more.

The use of those in the clinic has evolved pretty rapidly over the past three, four, five years. In my own practice five years ago I was certainly not routinely recommending that kind of testing. But today, particularly with patients with myelofibrosis, I am doing it much more frequently and the question of course is as you raised; what utility does it have in terms of prognosis.

And there especially I think in myelofibrosis, is where more and more literature has come out giving us a better handle on what effect these different mutations might have on prognosis. That’s why more and more I’m beginning to recommend this kind of testing for my patients with MF.

In the case of QV and ET, it’s a little bit further behind in terms of data to indicate what these different mutations might mean, but we have also seen more literature come out, not as often but do consider that kind of testing for those patients as well. In every case it’s kind of an individualized discussion with the patient. I always start out with how much do you want to know. Marsha said I want to know everything, so that’s the kind of patient where you say alright, well, maybe let’s do this.

Others say well, I don’t really necessarily know I’m going to interpret this; it’s alphabet soup. Do I necessarily want to know what the statistics say to expect in 20 years, etc.? Again, it’s an individualized decision with every patient.

Andrew Schorr: Dr. Moliterno, there was another patient who was going to join us who couldn’t make it because she’s being scheduled for a transplant. She’s getting her life in order for that; someone with I think myelofibrosis in the Seattle area.

But she did have three mutations identified, so let’s see if this makes sense: ALX1, if I get it right, TP53 and SFB1, if those are other ones? So the fact that she has this sort of alphabet soup, does that mean that that meant you’re headed for transplant because that shows up? You know, one knows is more – more weighty, if you will.

Dr. Alison Moliterno: This is knowledge that we’re kind of pulling in as we speak, and that the meaning of more than one mutation, different types of mutations do seem to have prognostic significance.

So as we’ve learned that generally the more mutations you have, more individuals at a certain point of time generally is concerning. It means that there’s a lot going on in that stem cell and that maybe there’s some instability to allow these mutations to occur. And then it does matter which type. Some mutations seem to have more independent prognostic than others. ASXL1 tends to be one that is seemingly more associated with developing myelofibrosis. SF3B1, one of those she has, may be a less negative prognostic indicator.

But again, these are important and having three at once is a concern, and it sounds like a reasonable plan to move forward with transplant because we understand that we don’t really have a medicine that can address all of those lesions and that this is more high risk disease.

Andrew Schorr: I want to remind our audience a couple of things. One is you’re hearing how sophisticated the testing is, and then you can imagine the interpretation.

We have two noted experts. The typical hematologist is not going to see this very often. So whether you go to Washington University, I go to UC San Diego, Marsha goes to the Lurie Cancer Center, Dr. Moliterno is at Johns Hopkins. You know some of the others where you go; you want to consult with an MPN specialist. As the data comes back, what does it mean for me now or on your journey in the future.

The other point I wanted to make is of course we want to take your questions. So send them to MPN@patientpower.info and our wonderful MPN community manager, Jamie, is standing by and she’ll be forwarding these to me. Obviously, a lot of you ask very personal questions; what should I do, Dr. Moliterno, Dr. Oh; I’ve got XYZ. And that’s not fair to do that here, so that’s our disclaimer. You want to go back to your MPN specialist – it could be one of them – to discuss it.

We did get some questions in earlier. Dr. Oh, Tammy wrote in and she said can you provide more information on being PV JAK2 negative? She says I know we’re limited in number compared to other patients. It would be nice to know the basics. How much more different are we and is our treatment any different? So, JAK negative PV.

Dr. Stephen Oh: That’s a great question and it’s a challenging question. I would say that in part because we know that in the case of PV, at least 95 percent or greater of patients with bonafide PV carry the JAK2V617F mutation and it’s at least 95 percent; it may be higher than that. And even those that are negative to the JAK2V617F mutation, there’s another small group, probably less than 1 percent, who carry an alternative JAK2 mutation, an exon 12.

 So between those two, patients with PV, again the vast majority do have a mutation in JAK2. That does leave a small sliver that you could call JAK2 negative PV, and there – it’s sort of being a skeptic – the first thing I say when I’m asked to evaluate a potential case like that is am I convinced that is the correct diagnosis? Do they truly have PV versus a potentially secondary cause of erythrocytosis?

And so there, sort of again you have to rely on the old school diagnostic criteria; do they otherwise have the features of the disease? Does the bone marrow, is it consistent with the diagnosis? Are they like a classic patient in that they have a low epo level, etc. But to get to more specifically to the question, if you’re convinced that that’s the correct diagnosis, essentially I treat the patient the same way I would treat a JAK2 positive PV patient.

In other words, I would use the same kind of treatment calls in terms of a hematocrit less than 45, treat them with cytoreductive therapy and the appropriate circumstance if they’re considered high risk, if they have had a prior history of thrombosis; aspirin considered standard therapy for these patients. Again, if I do believe that is the correct diagnosis, I essentially treat them similarly to patients with JAK2 positive PV.

Andrew Schorr: Okay, and Alison, do you concur in that?

Dr. Alison Moliterno: I do. I think we have a name for the disease, polycythemia vera, where you make too many cells due to an inherent stimulus of the bone marrow. I think now in this age, we are really coming to redefine PV as the disease that has mutations in the JAK2 gene. I’m always concerned when someone has been diagnosed with JAK2 negative PV because as Dr. Oh says, maybe they have something else.

A couple circumstances that I’ve observed is that sometimes the diagnostic testing, when it was done and it was done with JAK2V617F testing that was not sensitive enough. So again we have this issue of how much of this do you have? And some PV patients can have very low levels of the JAK2 mutation that if you use an assay in a laboratory that wasn’t very sensitive and you only detected levels of 10 or 20 percent, they would be read out as negative. That’s happened in my practice a few times where patients went high and low all over the place trying to get a diagnosis; JAK2 negative. Finally when a more sophisticated or sensitive test was done, they’re positive.

The other issue is that there are other mutations aside from V617F in the JAK2 as Dr. Oh said; there’s exon 12 and then there are some others in various parts.

So when we do some of this more expanded molecular profiling, the laboratories are able to look not just at the V617F site, which is where most tests – they only tell you yes or no at that site; but they’ll look at the entire part of the coding region of the JAK2 gene. You’ll find patients who have an unusual mutation down the way that’s like – And I think it’s important because there are some people who really don’t have a myeloproliferative neoplasm; they have something else and they’ve been told for 25 years that they have PV.

And it is nice to either make that diagnosis or not. And so I think Stephen has been in that situation also, where maybe they were labeled because that was the best information we had at the time, but they really should be reevaluated.

Andrew Schorr: And I think that’s the point for our audiences. You with the best testing, with the best specialists you can get to, you want to know what you’re dealing with; what is your situation.

Here’s a question we got so Marsh, just for you. You mentioned at the beginning, Marsha, that you have CALR type 2. Can you describe that? So let’s make sense of that. There was a support group leader, Kim, who wrote in. Kim wanted to know how do CALR types 1 and 2 manifest and progress? Dr. Oh, what’s the difference between CALR1 and CALR2? What does it mean?

Dr. Stephen Oh: There are a variety of different types of mutations in the calreticulin gene, but the so-called type 1 mutations are the most common and the type 2 are the second most common; slightly different. Functionally they may have slightly different effects, although I think as a class, these calreticulin patients have more similarities than they do differences.

But there has been some literature to suggest that overall, calreticulin mutations are felt to be associated with a more favorable prognosis, at least compared to patients whoa re JAK2 mutant or perhaps triple negative. But specifically those that have the type 1 calreticulin mutation, the data is strongest that they have the most favorable prognosis. So based on that, you could say – the simplest thing is to say if you’re calreticulin mutant, you have a more favorable prognosis.

But perhaps the more nuanced is that that is particularly so for those that have the type 1 calreticulin mutation. In Marsha’s case it’s interesting, and to me a little bit of a paradox in that type 2 calreticulin mutations are, relatively speaking, more common in ET than they are in myelofibrosis.

So in that sense it’s perhaps not surprising that she has the type 2 calreticulin mutation. But overall, of course, ET has a more favorable prognosis than MF so it’s a little, in that way, a bit of a paradox. And the other way to look at this, and this has certainly happened for myself and I’m sure it happens with Dr. Moliterno is these patients with ET or myelofibrosis who were diagnosed many years prior, before calreticulin testing became available, you then tested for the mutation and confirm they were calreticulin once that test became available.

It’s one of those sort of: well, I just confirmed what I already knew which is that they had a more indirect course over these many years.

Andrew Schorr: It’s just amazing. Fortunately we can talk about this, and hopefully the word better prognosis sounds ] great.

So I, with primary myelofibrosis diagnosed with the JAK2V617F gene, Dr. Moliterno. But when you talk about prognosis, now you’re introducing medicines that we haven’t had that long; like for me. I’ve been on ruxolitinib now four and a half years and it’s been working. So how do we – when you talk about prognosis related to genes, though, that relates to what treatments you have, right?

Dr. Alison Moliterno: Right. We have a lot of work because these genes do have meaning; what version you have, and they’re going to have meanings in terms of prognosis but hopefully also we’ll start to gain information about really how you respond to therapy. So far, it seems that it doesn’t matter too much whether you have JAK2 or CALR mutation in response for  ruxolitinib.

But I think as we extend or molecular profiling, maybe we will learn that some lesions are less responsive or less favorably responsive to have some of these agents, and might be more responsive to agents that we have in the future. So I think we have to use this information both diagnostically, prognostically, and also just kind of monitoring our treatment expectations to some of these new agents.

Andrew Schorr: Right, it’s a moving target and I know you have a few things in trials. So just to tie the knot on testing, Dr. Oh; somebody wrote in and said: look, my doctor doesn’t require genetic tests. Where do I start and how do I ask for it? Because we’re hearing the two of you saying it’s pretty standard for you to get a clear picture of what the situation is. So is, how shall I say it, self advocacy related to testing today for an MPN patient important?

Dr. Stephen Oh: I think it definitely is. These diseases, while they’re not super rare, they’re not as common as hypertension or whatnot. When you go to a hematologist or oncologist who does not see very many of these types of patients, they might not be TransDigm on the testing that’s available. And so from that standpoint, I think certainly self advocacy is important. This has been emphasized already but getting to an MPN specialist is important.

If we’re talking about in the workup stage, it’s just sort of imagine different scenarios. There certainly could be a situation where the physician, whether they’re an MPN specialist or a more general hematologist or oncologist; they may not feel there’s a testing and that could certainly be the case.


But if there is a strong suspicion of a possible MPN, then I think there’s no question this kind of testing should be done. Even in the situation I’ve encountered with some patients where the insurance may require preauthorization, if you go through that it’s almost never rejected.

Andrew Schorr: Dr. Moliterno, here’s a question we got in from Jane. Jane writes: my understanding is that JAK2 is an acquired genetic mutation, and you both spoke about that; not inherited so we’re clear on that. Is it known what variables cause this mutation? I got the impression from what Steve said, no. But then she asks; can this gene expression be reversed?

Dr. Alison Moliterno: Right. First, why did this happen. I always joke with my patients; I tend to think MPN patients tend to be the most highly educated, intelligent, beautiful and have healthy lifestyles; why would they get this? MPN or not, disease is a lifestyle or other processes that we can sort of point to. I think in terms of if we just focus on JAK2V617F, that’s an acquired mutation in the bone marrow stem cell, but we’ve come to learn that this is a fairly common mistake, acquiring this mutation.

So if you look at my bone marrow stem cells, you can find evidence that this occurs frequently as a mistake; almost like a typing error that we all make on our keyboards, and that this happens at a fairly high rate. Most of the time as Dr. Oh mentioned, it is deleted or it’s in a cell that doesn’t have a long lived lifespan so it really doesn’t propagate in the bone marrow.

 Some fascinating studies looking at the cause of this; what are the factors? So, this Danish study looked at 43,000 individuals that participated in a healthy Danish lifestyle activity. They said they had stored DNA samples from blood. These were well people; they did not have myleoproliferative disease. But they found that they could detect the JAK2 mutation, V617F in a reasonable percentage of these well individuals, and that this was more prevalent the older they got. So that over 80, I think it was .2 percent of individuals actually tested positive for this. They were able to look back and show that yes, most of these people didn’t have an MPN, although some of them did have higher blood counts.

When they followed them, some of them did go on to develop MPN. But the point of that is wow, this is a common, natural occurrence and it most strongly associated with aging. Most MPN patients are in their mid 50s when they’re diagnosed; some very young and some are much older. So again, while gee, 50 isn’t that old, 50’s not that old. So again, there must be other factors that allow that to occur. And these large population studies, I think smoking has been an association; again maybe helps accelerate that mutation growing.

There’s host factors, and that maybe we have reasons that we will make that mistake more often; s genes that we have perhaps that we’ve inherited that influence how well we have integrity in our DNA. So that just gets a little to why did this occur.

Andrew Schorr: What about turning it back, though?

Dr. Alison Moliterno: Right, turning it back and I think this is another thing that is important. Again, when we think about surveillance, we do know there are some therapies that can specifically turn down or squash that clone and I think many of us have heard or even experienced patients who are on interferon, or pegasys, pegylated interferon. And we can see that if JAK2 disease can go into a hematologic remission and even molecular remission that the JAK2 clonal burden reduces and may even go to zero.

This has also been shown with CALR mutation positive individuals in small studies that perhaps we can suppress that. So we hope someday to – it’s still a little frustrating; not all patients have that benefit. It’s not clear which patients will go into these molecular remissions of turning it down.

But I think we will get there and we hope that JAK2 inhibitors would have that effect. I think the data still there are not pointing in that direction, but I think we will ultimately be able to actually target that clone and control how it expands and turn it back.

Andrew Schorr: So Stephen, take us into your labs and into the research that’s going on around the world. How fast is this changing now? Alison talked about 2005 with JAK2 discovery and you had CALR and some of these others. What’s the rate of change now?

Dr. Stephen Oh: I think there’s different perspectives you can look at this. For those of us that are doing laboratory research, we feel in the field that things have progressed quite rapidly.

To go from 2005 discovery of the JAK2 mutation to small molecule inhibitors going into patients I think within two years or less to this one drug being FDA approved a few days later; that pace of discovery and development has been quite rapid. The identification of the calreticulin mutation in addition to MPL, those are really landmark discoveries in this field.

For patients, I think the perspective might be that wow, I wish it could move faster and we kind of know as a class in general what JAK inhibitors do; can we move onto the next level, or next phase, or next class of treatments? And I think there is where my long term outlook is very optimistic, but in the short term we don’t really have that  kind of next candidate clearly identified as to what to do next after the JAK inhibitors.

Andrew Schorr: Dr. Moliterno, we always talk about clinical trials. This relates to the progress you all are trying to make. We’re your partners in that. As you do the testing and you say oh, now we see this gene, and we see this one and this one and we’re trying to figure out who’s the bad guy, or is this new one a factor that we’ve identified? So what would you say to us as we lived hopefully long term with these conditions about considering being in a clinical trial to help you make these discoveries?

Dr. Alison Moliterno: We have had great support from our patients, not only in participating but also helping design these trials or partnering with us. As Stephen said, these are rare diseases so we don’t have 50,000 individuals to test whether aspirin works or not like you can in a cardiology trial, and get that answer in a year and make a difference for individuals.

I would say that the trials now are going to be a lot more molecularly based. So instead of just disease, MF yes or now; these trials are now going to have the molecular profiling and response to therapy as part of their design. I think that will give us a lot more information overall than we’ve had in the past. So there’s many benefits to this molecular revolution.

One is understanding the cause of the disease, the other is monitoring it over time, and then response to trials which individuals respond to; which therapies. I think we’ve all seen the television ads about Keytruda and patients, as you mentioned early on with different solid tumors and particularly lung cancer, and how really the profile of that tumor needs to specific targeted therapy, and that’s what we want for MPN.

 Then now we’re even learning that it really doesn’t matter where a cancer may have started; if it’s in the kidney or in the lung, that again the molecular – the drivers of that indicate that you may respond regardless of what organ it started in; it’s really the lesion that you’ve got. And I think we will be bringing that to MPN patient trials.

Andrew Schorr: I’m involved in an initiative called Precision Medicine for Me, and it started in lung cancer but it is about this testing to see is there either existing therapies or investigation ones that line up. Or F dot now and as you know one of the major cancer medical societies called ASCO, American Society of Clinical Oncology.

The whole mission of the new president, a guy named Bruce Johnson from Dana Farber in Boston, a lung cancer specialist, is that these precision medicine approaches of each patient and their doctor knowing what are they dealing with at the molecular level to push that out throughout oncology; certainly in the U.S. if not worldwide. So I think we’re all in this together. Marsha, you’ve been listening patiently.

Now you’ve had this transition from ET many years, which Stephen was talking about we know often a very good prognosis. But then it changed, and a little scarier. I’ve already started that point, myelofibrosis. But when you hear this, how do you feel, just listening?

Marsha: I think when I was first diagnosed I was scared to death. But I think through education, I’ve learned to calm down and I just try to tell myself that this isn’t a sprint in my case, hopefully it’s going to be a marathon.

And until then, I’m just going to learn what I can do to help myself. I’m very curious about additional mutations; however my doctor said that really would not affect the treatment I would be currently undergoing. And the big thing, insurance, has come about. He’s very concerned about whether or not insurance would cover the cost and the value of it.

Andrew Schorr: Right. Stephen, is this – it sounds like maybe we’re making progress with insurance companies; that they want us to get a clearer picture with our doctor? What’s your take on that now?

Dr. Stephen Oh: The driver mutations, the JAK2, MPL< calreticulin testing, I think it should be and almost always is covered by insurance.

But when you get into the more extensive genetic testing, that’s where the insurance companies will often balk at covering it. Then it becomes somewhat problematic as to is this really worthwhile. Obviously that the costs for it and for any particular patient can vary in terms of what insurance will cover, what the copay is, and what they can reasonably afford. In general, while I do believe that there’s much utility to this kind of testing these days, if the cost is prohibitive I do not push it and I certainly do not think it’s mandatory.

Andrew Schorr: Dr. Moliterno, and I’ll mention to our audience we have a few more minutes; if you have a question and we haven’t covered it, please send in your question to MPN@patientpower.info, MPN@patientpower.info.

Dr. Moliterno, so we have the JAK inhibitor now, ruxolitinib. There are others that are being tested in various trials. As you look not just at the genes but at the treatments, are you fairly encouraged there that you will have a broader array to line up with people’s different situations, and also what the side effects of treatment, if somebody gets anemic or whatever their profile is?

Dr. Alison Moliterno: Yes, I am very optimistic. I think many of us, again if you look back at where we were five years ago in terms of the options that we have and where we assume we’re going to be in five years, hence I think there’s lots of room for application of these therapies, for combination therapies to use therapies together, even the ones that we have. So I’m very optimistic.

And I think I would say it is very anxiety-provoking to hear you need molecular profiling, and yet your doctor is saying we don’t really need that, or we’re concerned about the cost, which is certainly a concern. One thing I always say is that’s fine; the molecular profiling isn’t going to go away as an option, and the cost will come down in the next few years. We are now able to do things that we couldn’t even imagine we could do clinically in terms of looking at all aspects of genes, and this cost will come down.

So I would say to, for instance Marsha, yes we may not need it today but we can always get it in two years when things are different in terms of the availability of it and the interpretation of it. So again, I think it is reasonable to say your treatment is this, you’re responding well; happily we don’t need this at the moment.

I would agree with that, but I’m also certain that in three or four years, we won’t be having this discussion so much about the cost of this testing.

Andrew Schorr: Dr. Oh, here’s a question we got in. you’ve got to decipher this one for us. We have some really smart people out there, like PhDs. Is a germ line ASXL1 mutation a high risk or detrimental factor in the same way as a somatic mutation? So what’s germ line, what’s somatic, and is this germline ASLX1 mutation bad news, basically?

Dr. Stephen Oh: That’s a great question, and I think it also connects to a broader question. But to first answer you, talking about our acquired mutations which is the same thing as somatics; somatic means acquired.

If you’re talking about a germline mutation, in this case ASX01, it’s not the same thing as an acquired or somatic ASX01 mutation, which is what we’re generally referring to when we talk about that gene and its affect on prognosis. That also connects to the more broader point which is that the devil’s in the details.

Whether it’s ASX01 or another gene, the exact mutation may matter a lot in terms of what the significance you attribute to that. In many of the labs that do this type of testing, they will have a column for each mutation where they’ll make a call as to what they think it’s significance is, and they’ll say yes, pathogenic or it will say no pathogenic, or it will say uncertain. Part of that interpretation depends on whether it’s the germline or somatic AKA acquired mutation.

Oftentimes they can’t say for sure because the only way to determine that conclusively is to test tissue that’s not from the MPN. So, sometimes it’s uncertain as to even whether it is germline or somatic/acquired. So again, just to be clear on this particular question; if it’s thought to be a germline ASX01 mutation, it’s unlikely to be relevant or have a prognostic impact on that particular patient.

Andrew Schorr: So Dr. Moliterno, the other question you must get from people is do I have to worry about a family member? Because when they start talking about genes, you’re talking about what your hair color is, or hairline as I was joking with Stephen, or whatever characteristics herein are hereditary.

But then we’d say gee, is there a hereditary factor to an MPN?

Dr. Alison Moliterno: That is a very important question, and long before the JAK2 discovery, we realized that about 10 percent of individuals with an MPN will have a first or second degree relative with either an MPN or another cancer. So there does seem to be heritable factors at play here. Some of the interesting – and again, it’s not because you inherited – in your individual case you inherited the JAK2 mutation from the germline directly from Mom, but you inherited a risk of acquiring it.

We’re trying to understand that and again, what does it relate to; does it relate to germline variation in genes that allow this to occur, that allow you to get mutations in blood stem cells or in other tissues?

So yes, we are still working on that. It does seem to be a component of that. And that’s not unlike CLL, chronic lymphocytic leukemia also has sort of a familial –

Andrew Schorr: And I have that, too. I’ve got them both. I understand. So I think about that all the time. Marsha, you have children, don’t you?

Marsha: Yes, I have two children. But I think even more importantly, I have a cousin who has CML and another cousin who had stem cell transplant for AML. So I think that’s interesting.

Andrew Schorr: This is all in the hematology world, so Dr. Moliterno, do we have, Marcia or me, with two blood cancers? And I have three kids; what about this and is there a testing they should have, or how do we go forward?

Marsha: We don’t have – I would to recommend that they need a JAK2 test or specific MPN testing. If they have normal blood counts and they’re well, they don’t need to be evaluated for disease at the moment. The question is are there family genes that need to be elucidated, and if you have a lot of cancer in the family, so for instance families that have a lot of breast cancer, we often will send them for genetic counseling to understand what their particular risk is. And in breast cancer and some other cancers, we do understand some genes to test that can give us that information; familial genes. So far in the MPN, we don’t really have the knowledge of which genes are at play. 

Andrew Schorr: Dr. Oh, any comment on that because I’m sure you get the same questions. People say oh, my God, should I worry about family members?

Dr. Stephen Oh: Absolutely. It comes up pretty routinely and just to echo Dr. Moliterno, I generally do not recommend any special screening for family members, of those who have an MPN. I would also point out that even if there is, certainly it’s established that there is a slight increased risk for family members of patients with an MPN. Even if the risk was, let’s say, four fold higher for a first degree relative, the overall risk of developing MPN is so low that that overall risk for a family member is so unlikely that they’re going to develop an MPN.

Andrew Schorr:  Really? That gives some comfort; maybe you too, Marsha.

Marsha: Certainly.

Andrew Schorr: We’ve covered a lot of ground over the last hour, and I think on a very important topic now as mirroring the progress related to some treatments either approved or developing is, understanding our slice of an MPN, and the working with you on monitoring that and how does that relate to care. We have two noted experts with us who are helping propel this forward. So we’re your partners in helping that. Dr. Stephen Oh from Washington University and the Siteman Cancer Center, thanks for being with us once again and giving us of your time; I really appreciate it.

Dr. Stephen Oh: My pleasure.

Andrew Schorr: Okay, and Dr. Alison Moliterno, being back with us again from Johns Hopkins in Baltimore; thank you. Thanks for both of you; your very clear explanations, and Marsha Krone, we learned a lot, didn’t we Marsha?

Marsha: We sure did.

Andrew Schorr: Okay. Marsha’s my partner here; she’s done it twice and we’ll have you back sometime, Marsha.

Also, we should tell you Marsha is a very active preschool teacher so she has these little rug rats running around all the time, and thank God you have the energy to do that and I’m really glad you do, Marsha.

Marsha: Me, too.

Andrew Schorr: All the best to you. Well, this has been a wonderful program. We want to thank the Patient Empowerment Network for leading the way in this series, and Incyte Corporation for its support of this educational activity, and Patient Power our wonderful team Alan and Jamie who make it happen behind the scenes. We’ll be having more throughout the y ear. We welcome your questions; always send them to MPN@PatientPower.info.

And all of us moving forward living with an MPN, we’re going to live well and we have wonderful physician partners to help us do that as they understand the genetics and all those people working with them to develop therapies to help us live a long and strong life. Thanks for being with us in Carlsbad, California near San Diego.

I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.

Living Well with MPNs – Tips and Strategies for Managing Symptoms and Side Effects of MPNs

Tips and Strategies for Managing Symptoms and Side Effects of MPNs

As part of our Living Well with MPNs webinar series a panel of MPN experts and patients discussed managing life with an MPN. The panel shared advice on managing fatigue, itching, night sweats, enlarged spleen and other symptoms. The experts explained why symptoms occur and stressed the importance of communication with your healthcare team. Tune in to learn more.

Living Well with MPNs – Strategies for Getting the Best Care

Managing Life with an MPN: Strategies for Getting the Best Care

In this “Living Well With MPNs” webinar, our expert panel featuring Dr. Laura Michaelis from the Medical College of Wisconsin, nurse Erin Blackwell from Levine Cancer Institute, as well as patient advocate Beth Probert, discussed managing life with a myeloproliferative neoplasm (MPN). The panel shared advice for finding a specialist, making informed decisions about treatment and monitoring progress of the disease through testing and check-ups. Tune-in now to hear tips for living well from the perspective of patients and healthcare providers.



Hello and welcome to this program, “Managing Life with an MPN; Strategies for Getting the Best Care.” I’m Andrew Schorr in Carlsbad, California and living with an MPN, myelofibrosis. The Living Well series is a Patient Empowerment [Network] program produced by Patient Power, and we thank Incyte Corporation for their support for this series. We’ll be doing several programs during the year so be sure to be signed up with our alerts and you’ll always know as we continue.

We have some great people with us today around the country. I’m in Southern California, northern San Diego County. Now let’s go to Milwaukee, and I want to connect with our friend Dr. Laura Michaelis, who is at the Medical College of Wisconsin. Laura, thank you for being with us on Patient Power and our Patient Empowerment program today.

Dr. Michaelis:       

Absolutely, I’m pleased to be here. I wish our weather was as good as yours must be.


Yeah, it is nice. And also I should mention Dr. Michaelis is dealing with a cold, so if she sounds a little stuffy, doctors get sick, too. But thank you for being with us. Now let’s skip down to Charlotte, North Carolina and the Levine Cancer Institute and that is Erin Blackwell. Erin works with Dr. Michael Grunwald who we know well there. Erin, thank you so much for being with us in Charlotte today.


Thank you for having me.


Erin of course deals with Dr. Grunwald with leukemia patients and myeloproliferative condition patients all the time, and won an MPN Heroes Award this past year at the American Society of Hematology meeting for her dedication. Okay, let’s go back to California. Beth Probert is with us from Oxnard, California. Beth is a PV patient and she is just north of LA in Oxnard. Beth, thank you for joining us.


Thank you so much for inviting me to the panel.


Beth, let’s talk about your story just for a minute. And that is you’ve been living with PV for what, about a year or so, now and you’re 55?


That’s right; just about a year.


Okay, how did that diagnosis happen?


Well, it was a little crazy. It was during a very challenging time of my life.

I was dealing with my daughter’s mystery illness and sort of forgot about myself, and finally went to have a CBC with a new primary physician. Somehow, a gynecologist – I was visiting a day before I was to get the results from my physician – had those results, and he saw them and freaked out, and pretty much told me to get my affairs in order.


That is scary for you. So who told you that you had this fairly rare condition, polycythemia vera; where did that come from?


Well, the gynecologist hinted at it and of course I fled his office and got my primary care physician on the phone. She called me down a little bit, told me to come in the next day and she suspected that it was that diagnoses but then arranged for me to meet with a specialist, which happened a few days later. So I had those few days of just pure panic.


Now, you subsequently connected with Dr. Ilene Weitz at University of Southern California, the Norris Cancer Center in LA. That’s worked out for you.


It’s been fabulous. I went there; it was a fairly long drive and I was telling myself I’ll get a second opinion and a third opinion until I find the right doctor, and I was lucky to find the right doctor.


We’re going to come back to how you communicate with your doctor and a little bit about the treatment you receive and how it’s working. But the thing is, you’re doing well now with the right healthcare team. You’re at peace, I guess, with your diagnosis; you’re going on with your life.


That’s absolutely correct, Andrew.


Okay, so Dr. Michaelis, that’s where we want to get everybody to is connect with the right team and doing well with modern medicine. So first of all, she mentioned about connecting with a specialist. You’re a specialist.

There are not that many doctors who see MPNs. Is seeing a specialist, at least having a consultation, knowing what you know about the field today, is that important? You’re muted, Laura. Hit the mute. There you go.

Dr. Michaelis:                      

Sorry about that. I would absolutely say yes, at some point early on seeing a specialist is important. One of the things is Beth’s story isn’t that unusual. The findings in a CBC of something that seems very off, whether or not it’s a very high platelet count, a very high hemoglobin or hematocrit can be pretty unusual for some doctors to see and know how to deal with. Sometimes they respond relatively drastically when that’s not necessary.

I think one of the best parts about a specialist is you’re seeing somebody who’s seen multiple patients with your presentation, with your symptoms, who knows when to be alarmed and when not to be alarmed. So Beth did exactly the right thing, which was make sure she then grounded herself with her primary care doctor, and I’ll say most of the patients that get referred to me are either referred to me by a primary care doctor, or sometimes by a specialist who might be a hematologist/oncologist.

But this is a rare condition even among people who see heme and oncology, so sometimes a hematologist/oncologist will want them to see me because I see this very routinely, and have seen patients at all edges of the spectrum.


Of course then as we talk about MPN, so everybody’s straight on this and some people may be new to it; talking about ET, essential thrombocythemia, polycythemia vera, which is Beth’s situation; and myelofibrosis, which has been my diagnosis since 2011.

In this program, we’re not going to really get into treatments and genomics and all of that. We’re really going to talk about how do you live well and get the best care. And it’s not just your relationship with the doctor. So, Erin, let’s talk about that. You work hand in hand with Dr. Grunwald. You’re part of the leukemia doctors there and the doctors dealing with blood cancer. The nurse plays a key role, and that’s part of the dialogue, right? And you’re specialized.


I think so. I think it’s a very different role than the provider, but we are healthcare providers also so we get to nurture the patients in a little bit different way. We’re not diagnosing but I think we’ve spoken about this before; patients usually have a very good relationship with their provider but they tend to open up to the nurse or the person that they get close to, which oftentimes will be in the office setting, the nurse.

So I think I’m able to glean information that the provider didn’t about symptoms that they’re having, that maybe they didn’t share with the provider; medication issues that didn’t come up.

So I think our relationship – and I’m the bridge, is sort of how I phrase it to patients. They can always go through me to get to the provider. If they’re not sure they need to contact the provider; I’m sort of the middle man.


Let’s start at the beginning. Beth, when you’re OB/GYN was freaking out if you will; did you see those blood test results and see how abnormal they were?


I absolutely did, and I was joking with you earlier that not only did I see some highs on there; I saw “critical” written next to several of those results. So that was extremely alarming.


Dr. Michaelis, most of us with any of these conditions see Hs and Ls and critical that she saw; notations from the lab. What does that mean to you?

Because we start freaking out until we learn more.

Dr. Michaelis:                      

Of course it’s important to remember that when somebody comes up with what is normal, it’s done by having let’s say 1,000 people go to the hospital, have their blood drawn, and then a bell curve is written as this is what the normal hemoglobin is. What’s important is not so much if somebody is one or two points outside of the edges of that; it’s important; what it is relative to Beth. So for example, if Beth starts at a given level and then over time, her disease gets under control, she may still be slightly high or slightly low in some zones.

But relative to her, the disease is getting better. So we don’t really pay attention to the highs or lows very much; that’s against a huge, general population. What I’m really interested in is what do Beth’s labs look like compared to where they should be, or what it would mean if her disease was well controlled.


So you deal with that, too, Erin, is people have a test and they’re alarmed. You often have to, as I say, bring people back down to earth, right?


Yes, and unfortunately when we print labs for patients, it actually will print out “high, low, critical” so patients do become frightened. We have a really neat tool on our computer system where we can graph counts over time. So I can show you from last year where you’ve started and where you’ve come to, so you can see the improvement, hopefully, and at times not improvement. That seems to calm nerves.


That does it for me. So okay, Beth, you started seeing a specialist and then you had a certain rhythm of visits now that you’ve had over the last year. How often do you go see Dr. Weitz?


I see Dr. Weitz now about every six weeks. At the [00:20:00] onset it was every two weeks and four weeks. But because I am doing much better, it’s now six weeks.


Right, and we should mention in your case, your one of the folks with PV who is on an interferon. The dose has been adjusted but it’s working well for you.


It’s working very well.


Okay, so Dr. Michaelis, let’s talk about how you establish a treatment plan. So we come in, you confirm the diagnosis, we have some tests. So, how does that dialogue go about not specific treatments but how do you establish a plan?

Dr. Michaelis:                      

That’s something I’ve learned as I’ve matured as a doctor, and I feel it’s something I’m getting – I hope to get better at. I start everybody by talking about what is the cause or what do we think the causes of the disease are. I think it’s helpful for people to understand the way the disease develops, what are the underlying levers and changes in the bone marrow.

And then we talk about 1) have we truly confirmed the diagnosis? Do we have all the tests we need? Once we get through step one, which is confirming the diagnosis, we then go through something called risk stratification. Risk stratification means that we look at what does the disease look like, what are the characteristics of the disease. Are there high risk characteristics or low risk characteristics?

We then look at the patient’s own medical history; their age, their other health issues, their what we call comorbidities; the other things they may be struggling with. And the combination of those two help me determine what’s the likelihood of something bad happening because of the disease, or how the disease interacts with the patient. Once we have that risk stratification, then I like to talk about goals. What are this patient’s goals? Some people want to do everything they can to eradicate a disease.

Some people, their important values are their quality of life or being at home with their families. I try and listen to their values and what’s important to them, and then with that, we think about this is the risk the disease poses. These are the goals that you have; what is our panel of options out here? What kind of arrows do we have in our quiver, and how should we choose that treatment based on what we can accomplish, what you want to accomplish, and what we ought to accomplish.

That ‘s the kind of dialogue, and I find that that conversation, not the one where you’re first diagnosed, but that conversation of the first discussion of should we start treatment, that’s one of my longest conversations. So I prep patients; this might be a conversation where you want to bring family members. This might be an appointment we’re going to make as a double length because it’s going to be a little bit longer. Sometimes we’ll have patients bring their iPhone or something so they can have other family members conference in.

But that decision about starting treatment and which treatment to go for and why is an important one. And finally, we end it all by what should we see if it’s working. So how are we going to measure that this treatment is working for you? What are the types of things we’re going to see, and when? And when will we know when it’s not working?

So I like to lay it out with saying have we gotten the diagnosis, do we have appropriate risk stratification, have we identified your goals, and what kind of treatments are out there that could accomplish your goals.


I was living in Charlotte for awhile so I went to Erin’s clinic and to see Erin and Dr. Grunwald. We would talk at each visit based on what Dr. Michaelis was just saying: how am I doing, how’s it going; bout a frequency visit. Sometimes I’ve had doctors say to me, when do you want to come back? Then I’d say doctor, when do you think?

Well, I think you should come back in three months. Sounds good to me, or should I come back sooner? Erin, you’ve been part of those conversations about frequency of visits. How do you as a team determine that with the patient?


I think it’s really; again as Dr. Michaelis was referring to, it’s a conversation had by the physician, the provider; what they’re comfortable with versus what the patient is comfortable with. At times, it’s that the patient would like to be seen more frequently than they really need to be for their comfort and their peace of mind. And the physicians usually are okay with that.

Then there are times when they want to go six months without follow up, and obviously with a lot of our patients, unless they’re just doing very, very well, that’s not feasible or responsible. So it’s always a conversation and I’m the one to make their follow up appointments and to give that to them when they’ll leave. So I’ll be the last line if they have an issue with it; they let me know.


Beth, how often do you go? How often do you see Dr. Weitz?


Now I’m seeing Dr. Weitz every six weeks, and I really took to heart what Dr. Michaelis and Erin just spoke about because it’s the process I went through. What makes it very comfortable for me now to go every six weeks, I know whenever I have a question I can reach out to Dr. Weitz through the portal email. And it’s amazing; she gets right back to me. So it helps bridge that time going from two weeks, then to four weeks, and now it’s six weeks. I don’t feel alone. I don’t feel like it’s too long because I know I could reach out to her and her support team, as well.


Okay, let’s talk about phone calls and emails. Dr. Michaelis, are patients able to call you? Do you communicate either directly via email sometimes or through the portal that maybe your institution has – many have it; I have it at UCSD here – about visits or connection, if you will, or questions with you or your team when you’re not physically there; when the patient is not physically there?

Dr. Michaelis:                      

Absolutely. One of the technologies that is possible now because of these electronic medical records allows what we call asynchronous communication. So you wake up in the morning and you’re much itchier than you’re used to, or you have a rash, you email me. You don’t have to reach me at that exact moment in time, but I will see it. My nurse sometimes screens it, and if it’s something she thinks is more urgent she’ll walk it over to my office or she’ll page me.

If it’s something that can wait, there’s a given period in the day when I take a look at the messages that have come in, that I’ve set aside and I’ll respond to them. Sometimes a patient wants to talk by phone, which is great. And that, I always ask them leave me a time that’s a good time to talk to you; best for me after 4, before 6. And that’s a time when I tend to be able to communicate with patients. I think one of the key elements is to remember, these are not for something urgent.

If you have chest pain, if you have severe shortness of breath, if your leg gets suddenly swollen; don’t expect these emails through the electronic medical record to be that timely because it’s often something that’s done as a routine part of the day but not urgently. Those should be done by a page, and everybody should have a way to page your doctor or their nurse through a triage system. Or, if it’s a real emergency, of course go to the ER or call 9-1-1.

One of the other things I do is I give my patients a stack of cards. Because if they’re being seen in an emergency room or somewhere, I want them to give my card to that doctor and ay: this is my hematologist, I have a rare blood condition; please page her. That’s because sometimes folks live far away from me, and so if they’re up in the upper peninsula of Michigan or skiing somewhere and they have an emergency; their bleeding risks, their clotting risks are unique.

I want people who aren’t familiar with this kind of blood condition to be able to call me any time and I can say this person has PV, they’re on a low dose of hydroxyurea; these are the things you need to watch out for. If the person needs to go to surgery emergently, this is what needs to happen afterwards. So I always have my patients carry a stack of cards to distribute. And I say don’t assume any physician knows about this condition; please have them contact me.


That’s a very cool idea. I hadn’t thought about that and they hadn’t told me that at UC San Diego where I go. So, now we’re going into travel season, Erin. So people may go far afield. Esther and I are actually going on a business trip to Europe; hopefully everything will be just peachy fine. So talk to me about travel.

People have anxiety with illness when we travel, and if we have a wonderful relationship with you or Dr. Michaelis, or Beth has with Dr Weitz in Los Angeles, when we get away from that tether it can be a little anxiety-producing. What do you say to people about travel, particularly as we’re looking at the travel summer season?


It’s usually a conversation at the appointment. If our patients are going to go out of town for any reason, there’s a risk of interrupting treatment or they need labs while they’re away; that’s something we can help them set up. We have a patient currently that travels to Florida every other week and is on treatment. So we worked with an institute in Florida to sort of split care. So it’s a conversation that needs to be have. And I think fortunately, our patients have direct access to us almost 24/7.

We have an Access Center that takes calls 24/7, and during the day will reach a nurse; at night a physician covers. They always have my email address, my direct phone number at my desk. So, we try to make ourselves very reachable, so if something does come up –

But as Dr. Michaelis was saying, if anything urgent and life threatening comes up; call us later and go to the ER first, that sort of thing. We reiterate those messages.


I’m going to come back to you in a second, Beth. Well, Beth, let me ask you this while I’m thinking about it. From the patient point of view, like I don’t know what your travel plans are. You’re giving yourself interferon shots. Do you worry about travel at all because of PV? How do you plan your life? Because you have your doctor visits, you’re giving yourself shots. How do you plan your life, and do you worry about disrupting that plan at all?


You know, on the onset I absolutely did. When everything is running your mind, and at the time I was traveling more. So my doctor actually talked to me about if I do need to take it with me, that the airlines, you know, what they require. And she urged me to check the airlines that I typically travel to get the instructions; does it need to be refrigerated, what are the security risks?

So, I sorted that out when I first went on the medication. I was doing a little traveling for business. And of course now that I’m on an every other week dose, it does make it quite easier. But I do urge PV patients to figure that out in advance, even if it’s just a slight – Maybe it might happen, maybe it might not but to be prepared in advance is something so important. So I did check that all out.


Laura, you were talking about eventualities that come up for patients and the communication among doctors. For instance, I have minor surgery that I’m trying to have happen. And so in my case as a myelofibrosis patient, I have lower platelets. And so I’ve got the surgeons talking to my hematologist/oncologist and they’re going to be prepared with platelets for the surgery so I can have the surgery; they feel it’s safe.

But they planned for it and they’re all talking, and that’s the kind of thing we need to ensure is happening, right?

Dr. Michaelis:

Oh my gosh, yes. I think communication between physicians is absolutely essential in this, especially when a procedure is elective. That means there’s time. Elective is a term we use when something can be done and planned in advance instead of emergently. We do know that when patients with PV, for example, go to surgery and their hemoglobin is very high, their risk of clots after the surgery or even problems within the surgery with the anesthesia can be higher.

So you want to make sure you’re going in – to the best of your ability, you’re going in with your blood counts well controlled and under optimal management. Same with platelet counts, which elevated platelet counts after surgery, can sometimes be a problem.

The other thing is that when your doctors communicate, it means that there’s a transfer of information, there’s a transfer of knowledge. And so that surgeon, when they go to see you and does his post-operation visit, it’s going to remind him: oh yeah, this patient has that rare condition; maybe I should call that doctor and just update them, for example.

So starting that communication early and that transfer o f knowledge is not only good for you, but makes sure that there’s a sort of routine – there’s a routine collaboration on a complicated patient.


So Erin, what do you tell your patients so that they get everybody working together? You try to do it within the hematology area, but somebody might have diabetes, somebody might have heart issues, somebody might have whatever surgery, procedures coming up. So how do you counsel people so that you know what this condition is, that we’re living with this hematologic condition is understood and proper communication happens?


Similarly to Dr. Michaelis, Dr. Grunwald and Dr. Gerber both give out their cards to every patient that comes to the door. They hold onto it and they know if they see another provider and there are ever questions, that they can give them the card or give them their information. Something we don’t think about all the time when we’re treating these patients with either acute leukemia or myeloproliferative neoplasms in this case, they oftentimes have comorbidities or other things going on that we have to also address and make sure they’re staying – if they do have databases, we’re monitoring their A1C and their sugars are controlled.

And just because they have this diagnosis in myelofibrosis, that they’re not forgetting to take care of the other parts of their bodies. We need all parts to work, so I think it’s really important when I see patients – I look over their labs and their vital signs and make sure we’re addressing the things that sometimes we accidentally tuck away, like if a patient’s blood pressure has been continually high and we’re not addressing, or if their sugars have been high and we haven’t checked an A1C.

I think the best thing we can do is educate patients to know those sorts of things and to know what to look for so they can be advocates for themselves. But I think it’s also important that we all are mindful of the different parts of the patient because most of our patients are pretty complicated. There’s not just one thing going on.


Right. I have a question for you, Dr. Michaelis. So frequency visits, just to go back to that, if you want to see me more often does that mean things are not going well and I should start – my blood pressure should go up and – you know?

Dr. Michaelis:

Not always. Certainly if I get worried about a patient, my solution to that is to pay more attention. So sometimes if I’m worried that somebody’s disease is progressing, I will see them more frequently. But more often, when I see somebody more frequently it’s because we’ve had a turn in the road.

It might be a change from hydrea to interferon. We might have changed the dose of interferon a little bit. I might be worried about –. Maybe it’s the time of year, for example flu season. A lot of patients in the fall, we have a lot more hospitalizations with all leukemia patients and also some MPN patients. So sometimes it’s just that – I usually, like Beth’s experience and Erin’s experience, the frequency of visits is often a conversation. I’m not somebody who can go to long without seeing my patients. I want to keep them close so that I monitor them.

But if somebody is getting labs, they live in the upper peninsula of Michigan, they’re getting labs every six weeks and seeing me every 12; that’s fine and just keep up with that.


Right. I want to mention to our audience, so we have time for your questions so send them to MPN@PatientPower.info. We’ll get to the ones we can today, and we’ll be doing a whole series of these programs and so we’ll just keep making sure that we cover what’s important to you. I want to mention in my case as a myelofibrosis patient, that Dr. Jamieson down here in San Diego, she has me go to one of their clinics within the UCSD system and get monthly labs. And then if there’s something she’s concerned about, they let me know. But otherwise, I’m on a three- or four-month schedule, whatever it may be.

Okay, let’s move on to some other things. We talked about the treatment plan, Dr. Michaelis; you talked about that. One of the things that can come up in treatment planning now today is hopefully we have a situation that continues to involve in MPNs, is clinical trials.

So you’re a researcher as well as an in the clinic clinician. So where does that fit in in the discussion, in your opinion, related to what clinical trials are happening, what might be coming, what should we put on the table for our ongoing discussion?

Dr. Michaelis:

Great question. I think there’s this false idea that clinical trials are something that are used as a last resort, and it turns out that that’s really not the case, not in MPNs and not in other conditions as well. So, clinical trials are where there’s a hope to either improve or change the standard of care. When a patient is newly diagnosed, there is oftentimes opportunities to be in a trial that might be providing the standard of care with something else, or might be testing some new agent against the standard of care.

In myeloprolifative neoplasms are one of the most novel agents; there’s a medicine called ruxolitinib which is the brand name Jakafi, and that was only approved because people participated in clinical trials and found that it was effective at the goals that were set out in the treatment of high risk or intermediate to risk myelofibrosis.

So when I talk to patients about clinical trials, I frame it again in terms of the risk stratification, what are our goals, what can we reasonably hope to change, and when should we try and do that; and I put that in the panel of options. So option No. 1 might be standard of care, option No. 2 might be a wait/watching approach; let’s just observe for awhile.

Option No. 3 might be participating in a clinical trial. Clinical trials become more important, I think, when the standard of care options haven’t worked, So in a patient that may have progressed through several lines of therapy. so in a patient that may have progressed through several lines of therapy.

Then looking even farther afield for clinical trials, newer agents, agents that are brand-new out of the lab are often tested only in a handful of spots around the country. And for people with the desire and the wherewithal to look for those novel agents, again far afield; if that’s something logistically possible. And if it’s part of your value system to be involved in something very experimental where there’s no guarantee of success, then looking into clinical trials might be helpful.

Some people don’t want to be in an experimental situation, but some people find value in being part of the process to discover new drugs. And that’s something that’s an important thing to explore with your doctor.


I’m just going to make my pitch. I also have another blood-related condition, chronic lymphocytic leukemia. I was in a phase II trial for that.

I got the combination therapy ten years before it was approved by the FDA as a combination. So I think that helped with my longevity. I’m on ruxolitinib, the drug you mentioned. I was not in the trial but I got it early after it was approved, and I’m very grateful, very grateful. I met even who I think was patient No. 1, Mike down at MD Anderson, and I’m very grateful; I’ve given him a big hug, you know? And so I think it’s something to consider.

Your interferon is working for you, Beth, but there are other interferons in trials and other medicines in trials should you need it. What’s your take on trials? Because I know you’ve been going, looking at all our programs and learning about it. What’s your thought about it now?


Let me preface this by saying when I was first diagnosed, I knew I had to remain open-minded. There’s no black or white; there’s a lot of grey.

So I gave myself the commitment that I would listen to everything that’s out there that’s pertinent to me. And somewhat what Dr. Michaelis had said a few moments ago is let me identify your value system. So taking all that information in, I would absolutely consider being part of a clinical trial if it was going to benefit me or have the opportunity. And I agree again with Dr. Michaelis that it probably would depend upon where am I at. It might be working well for me today, but maybe six months, a year, two years –

The other thing I realized right away is that in as much as we all do have very rare diseases we’re speaking about today, things change. The ongoing research, what might be happening today, six months from now might be very, very different.

So taking all of that into consideration, and I do have a very strong goal for patient advocacy and hoping that my journey through this medical challenge is meaningful and could provide hope and care for others in the future.

Having said all of that, I would definitely remain open and just take the situation as it comes along.


Right. What a great attitude. So Erin, that comes up in your discussion. You have Drs. Grunwald and Gerber who specialize in this. I would just make a comment, so your doctors there, Dr. Michaelis in Wisconsin, other doctors we’ve mentioned along the way; these are specialists in these conditions. If you think about companies that are sponsoring trials, they’re going to go to these doctors and say would you be interested in doing this trial. So if you want to particularly have access to trials in MPNs, you want to be connected with the specialists in our conditions, right, Erin?

Because you have research going on there, right?


We do. We have several clinical trials open at the moment that are pertinent to this particular set of patients. We don’t have every trial that’s open, but they’re also familiar with what institutions do. So, if we have to make a referral outside because of patients interested in a trial that we don’t offer, and that’s something that we routinely do.

And I just want to point out; you mentioned travel and being prepared. Because of an experience that happened recently, make sure if you travel that you take your Jakafi with you if you happen to be on it, because suddenly stopping Jakafi is not a good thing, as we educate our patients.


And don’t put it in your checked luggage


Right, right.


Keep it right with you. I keep it so close to my heart, Erin, I understand. Jakafi, I know, it’s not something you want to stop.


Yes, especially suddenly. It should be tapered if it’s going to be stopped or else there are withdrawals.


No, I’m very careful about that. Okay. So Beth, you’re living with this diagnoses that you’ve had for a year or so. So, how have you gotten your head on straight about it to go on with your life?


Well, I knew right away that if I looked at my diagnosis as somewhat of a gift, and I mean that by I was running around, I had so many other priorities, I had no clue that anything was really wrong with me. And I shudder to think what might have happened had I not gone for that CBC. You know, I really had a very serious medical condition at the time.

And so I took the attitude that I need to be gracious I was diagnosed, because looking at the alternative, it could have had terrible consequences. And I realized – you know, it took me a couple of months to get my feet back on the ground, so to speak, to just be calmer.

And I really had to start doing some things that people had always said. Oh, you have to have balance in your life. Or you should exercise more; you need to take time out for yourself, or you need to meditate. And I just realized that I need to really be more balanced, mind, body and soul if I was going to go through this medical journey.

So I started doing some different things that worked for me. I wasn’t so good sitting there meditating, but I learned to meditate and walk. I started embarking on yoga. I really embraced myself in a plant-based diet for various reasons. It was working well for my daughter for her autoimmune and I thought there was a lot of merit for helping me. And with that came learning how to cook again; with cooking came more peace and time to think.

I know that’s sort of a long-winded answer but I had to do things differently to be able to understand that I want to live life to the fullest. And if I’m running around always worried, freaking out about this new diagnosis and my medical challenge, I wasn’t going to make it. I really had to be balanced mind, body and soul.


Well said; I think that’s true. So Dr. Michaelis, you have people come in. Whether you make the diagnosis or confirm a diagnosis, they’ve come from somewhere else and they’re pretty alarmed. The family members are alarmed as well. Yet, all of us want to take back control. We feel out of control; this disease we have never heard of. How do you help people? How do you counsel them so they can go on with their lives?

Dr. Michaelis:

One of the things I do is tell people that I’m paid to worry; you’re not.

My job is the worrying job; your job is the living job and so let me do the worrying. You know, I’m used to worrying about these things; I know what to worry about and that’s my job. So my job isn’t cure; I try and heal but I’m not a curer. I try to heal the best I can. If something is curable, I’ll do that. But I am good at worrying. So, that’s what I tell people to leave in the office.

The second thing is that most people have gone through episodes of their lives before where they’ve felt out of control, and things get you through that. Either your family, or the people you love that are around you, sometimes exercise or meditation. Sometimes it’s venturing back into positive habits like good eating like Beth was talking about, or being outside in nature. Some people are grounded in faith. Something that makes you feel bigger than yourself; those same strategies are helpful when you face the grief of a diagnosis like this.

And it is a grief. You’re leaving behind a perception of your body that’s not true anymore because you’ve been diagnosed with some crazy disease that you’ve never heard of. So it is a process. I would say Beth, three months is a great time to be able to have gotten grounded again, and I think the strategies that you used in sort of learning from your daughter is incredibly positive.

But you’re right; this is a new chapter for people. Like, you thought you were traveling along in one country and then the road took a turn and you’re in a different country. So you just have to sort of say well, I want to drive safely but I also have to enjoy the landscape here. So, that just means you have to adjust.


I’m just going to make a comment as someone now living with myelofibrosis four and a half years. So, it was terrifying and my spleen is somewhat enlarged so it’s a reminder that it’s there.

I have my medicine right next to my toothbrush morning and night so I’m reminded then. But the rest of the time, I just go about my business. And I think, and Beth you can probably relate to this, and I’ve said this a number of time. In our lives we have people say can you go on a hike with us, or can you come over for dinner, or can you take ten minutes and let’s get coffee? And often the answer is no because you’re so busy.

I’ve routinely tried to make my answer yes. And Beth, I don’t know if you, too, maybe you could say stop and smell the roses but it’s take time out to enjoy.


I could not agree with you more, Andrew. I realized that I was just going a mile a minute all the time, and putting things off and people off.

And you do, you really do reflect on who that inner circle is that you want around you, and making time for them and enjoying that time. So yes, I absolutely agree with what you just said.


Erin, I’m sure you’ve had patients who’ve seen Dr. Grunwald or Dr. Gerber maybe for the initial diagnosis. They’re really troubled. And then over time, how have you counseled people to help them really just go about their lives, enjoy their families, enjoy their work, travel, whatever is important to them?


I think that’s the key is finding out what is important to them, and then you can really help them understand that although this is a diagnosis that affects how they live the rest of their lives, and in no way should we minimize that. But we also want them to be able to do what you do, where you take your medication and you go about your day the way that you would like to. I think a large part of the reason our patients don’t always do that is how they feel.

A lot of times they suffer from fatigue, either from anemia or secondarily or just from the disease itself.

It’s hard for them to feel up to doing those sorts of things so I think it’s really important to find to what kind of lifestyle they lead, how we could maybe improve upon that, and then involve any members of the interdisciplinary team that we need to. Sometimes patients need social support, sometimes they need – we have a social worker on campus that’s able to help patients especially with that first visit it they’re having trouble coping.

We have resources available that can help these patients. But I think the key to it is understanding what life looks like to them, what they enjoy about it, what’s important to them, and how we can get them back to doing those things.


Amen. So Dr. Michaelis, let’s talk about communication, not just the emails and the web portals and phone calls, but sort of transparency in communication, if you will. So, that’s on a number of levels. You mentioned fatigue, Erin, and fatigue, I’m fortunate I think I really haven’t been affected by it in any big way.

Beth, I’m not sure about you but there are things sometimes that we don’t confront, or don’t make positive adjustments to. How do you help people first of all communicate about what’s really going on? You mentioned a phone call about itching awhile ago. But whatever the symptom may be and where you all put your heads together to say how can we help you live well, deal with this, improve it if we can, and if we can, what adjustments can we make? Let’s talk about that open communication.


Absolutely. One of the things is Erin is absolutely right; this cluster of diseases has a lot of symptoms. And it used to be that policies looked at the blood numbers and said ah, they’re not that bad; you’re fine.

It’s the work of Dr. Mesa who really brought this idea of symptom management and identifying and quantifying the symptoms that patients have, that has led us to be able to say the people with myelofibrosis and myeloproliferative neoplasms are more tired, they have more difficulty; we’ve heard about the itching and the bone pain. There’s also more difficulty sleeping, more chances to depressions, sometimes difficulty fulfilling work obligations. So, truly there are some symptoms.

Now, some of those get much better. They get better sometimes with medications, for example. They can get better if the anemia is well controlled. We do think that probably exercise is helpful, although there are still clinical trials going on with that. But your doctor is never going to know if you don’t tell them. And if the doctor doesn’t ask on a routine basis, and have you really used some metrics to quantify it?

So some of us use surveys. Every time a patient comes in, they might do a certain survey that says: in the last week, how often have you been in pain? For the last week, have you noticed depression? Or for the last month, have you found more difficulty sleeping?

Those kind of things, and we can compare just like you charted your CBC over time; you can also look at your symptoms over time and it’s something quantifiable. It also gives you a hard number to measure; is my treatment working? Look, you say you don’t feel differently but look what you were saying your pain was before, and look what it is over the last three visits. So that helps to really bring people back to the fact that while things aren’t perfect, maybe we’ve made some improvements.

But I absolutely think that not only keeping a diary of your symptoms at home, so if you just keep a little three-ring binder or something that says I notice that my migraines are happening at once a week versus twice a week as before; making sure you arrive at that doctor’s office with data in hand can be really helpful at grounding them back to the fact that this is a symptom-based disease, a lot. And if you don’t treat the symptoms, you’re missing a key part of helping that patient thrive.


Erin, you’re nodding your head. And I know when you walk into the Levine Cancer Institute, you give us a clipboard.

There’s stuff to answer, and they do that in San Diego. Maybe you have that, Beth, at USC in Los Angeles, as well. So that, really being honest, the patient, and maybe the family member saying – if they’re with you – hey, you really haven’t been sleeping well. You really have been avoiding taking a shower because you said you’re having itching. That’s important, right?


Yes, sir. And it’s sort of funny. These are constitutional symptoms that the patients feel. We give them an assessment every time they come to see us; one on their initial consultation that’s slightly different, and then subsequent follow up they’ll fill one out that is the square of 100, based on their symptoms. The max score, if they had every symptom at its worst would be 100; and if they had no symptoms, it would be a zero.

So we are able to track the progress. But it always tickles me that a lot of times the caregiver will fill it out on the patient’s behalf. Sometimes we might get more accurate information that way because the patients don’t want to complain, per se.

So the caregiver knows they’ve complained to them, whereas they don’t want to complain to us so it is interesting to see.


Okay, let’s go on and take some questions. And if you have a question, send it to MPN@PatientPower.info. Laura, this one’s for you. This is from Sandra. Sandra writes in: 2012 through a number of blood tests, I was diagnosed with an unclassified MPN. I see a hematologist once per year for blood work. My chart currently says MPN disease stable, and I’ve never been on any medication. Is it possible to be unclassified or are my doctors just waiting for the disease to progress?

Dr. Michaelis:

There is definitely a condition called MPN-NOS. That tends to be something called – it often is an MDS/MPN overlap.

I will tell you the World Health Organization recently redid their numeric – the way they sub-classify these. So one thing you might want to ask the next time you see your physician is, is my disease still classified as MPN-NOS? Or does the new WHO diagnosis, the new WHO classification give me a more precise definition? I will tell you also that sometimes repeated bone marrow biopsies, or at least a second bone marrow biopsy might be necessary to see what’s happening at this time.

Diseases evolve over time, so if it’s been five years since your last bone marrow biopsy, and if somebody is considering treating you, then I would certainly get a repeat bone marrow biopsy to get an accurate picture of your diagnosis.


Okay, here’s another question probably for you as the provider, here. I believe the name is Maria; could be Maria but I think it’s Maria. Or, we’ll call her Mari.

Does a B2 vitamin supplement, 1 milligram tablet a day orally, do any harm for a patient with PV? And then she also asks about other supplements such as valerian root or melatonin.

Dr. Michaelis:

About the B vitamins, I don’t know that it would do any harm. We do tend to avoid too many vitamin supplements in the early phases of these diseases because these diseases are where the bone marrow is growing on its own. It’s kind of like it stopped listening to the body’s controlling signals and the stem cells, which are the interior parts of the bone marrow, are growing without control and that’s why people’s hemoglobin or platelets are high.

So you don’t want to feed that. I don’t think it’s dangerous to take the B2 vitamin, but I also don’t know what help it would have.

With regard to a supplement like valerian root, that’s not really – I don’t know anything about that. What we have here, for example, is a specialist – is somebody who deals with alternative – she’s a pharmacist. She knows a lot about alternative medicines. And what I ask people who are interested in taking a lot of supplements is to have an appointment with her and verify that nothing is going to get in the way of the therapies that I provide. Because I’m responsible for the toxicities of any therapy that I administer. And so what I really want to make sure is that no supplements are going to hurt in that way.

Melatonin is a relatively common supplement. It’s excellent for sleeplessness that happens to be about circadian rhythm so your light exposure. I think it’s especially helpful in the northern part of U.S. I’m here in Wisconsin, and I’ll tell you it’s hard to readjust your sleep when you’re going from a 14-hour night to a 4-hour night based on where you live. It can be helpful and I don’t think that there’s much danger that’s been reported to melatonin when used as directed.


Erin, I know you have a pharmacist – I’ve met him – there at the Levine Cancer Institute. So checking in with the pharmacist about prescription medicines and supplements; that’s not a bad idea, is it?


We actually have four dedicated pharmacists to our clinic, but it’s not just us; it’s lymphoma, myeloma and leukemia clinic. But yes, we use them frequently. They’ll consult with patients and at routine visits, they’ll check in. they actually have the ability to make patients – they’re essentially really nice medication lists that tell them when to take their medications at the scheduled time. It’s a printout for them that helps them organize when to take their medications.

So the pharmacists are very involved, and if I ever have a question about a cold medication; will it interfere with the medication they’re on, or supplements, then I will start with the pharmacist and go from there.


Okay, let’s go on.

Here’s a question we got from Judy. Judy asks: I’m finding it difficult to coordinate care among my doctors. Do you have tips on accomplishing that? She say: not all of my doctors are interested in being part of these communications. So Dr. Michaelis, you passed out the cards but how do we make it happen when we, the patient, and maybe you helping us with a serious condition, know it’s really important?

Dr. Michaelis:

It’s hard to change other people’s behavior. I think you offer. I think another thing to do is when you go to your hematologist, ask if a copy of the note, the consultation note, can be also sent to you so you can keep at least copies of some of the written communication that’s happening.

You can’t fix bedside manner. You can find doctors who have good bedside manner, and don’t be afraid to shop around. Nobody gets offended; you’re not offending anybody.

If you find a doctor that doesn’t want to listen to the other people taking care of you, then that’s a concern. People should be collegial. You’re the only person in the room that matters so treat it like that.


Amen. Actually, we have an email from Charlyn that’s related to that. She has this question: What if your hem/onc doctor does not want to give you a referral, such as to a subspecialist like you? She’s saying we’re close enough to be seen by a specialist at Stanford, so in northern California, but need the referral to have it covered by our insurance. So the more general oncology maybe doesn’t want to let go, and you have to go based on insurance. Any thoughts about that?

Dr. Michaelis:

It’s not something that I encounter that much because I’m on the receiving end of that. I guess I would, like every human interaction, I would explore about why.

Why do you not think I should go up and see? If it’s about – I just want at least one consultation to make sure I’m keeping up with things – I’m not sure. It may be that the physician doesn’t think that your disease is serious enough to be seen by – that you need to be seen at an advanced or a tertiary care center. And then maybe there’s a limitation in the number of referrals you get and they want to wait until you actually need to be seen for something where things are going in the wrong direction.

But I would just treat your doctor like a human and ask them why not; let me know. And sometimes you even have to set up an appointment just for a conversation. Just say I’d like to set up an appointment to come in, have a 20 minute conversation where you just say this is what I want to explore with you; that kind of thing. When in doubt, just ask why.


Right. I think be a consumer, Beth, right? You’ve got to advocate for yourself.


That’s absolutely true. And you know, it’s important to educate yourself and as Dr. Michaelis said earlier, we’ve lost control when we are affected by these types of diseases. Sometimes that might be within the conversation, too, with your oncology/hematologist to say I believe I would have more control if I also explored having a consultation or working with an additional specialist. And it’s reminding your physician that it is about you gaining control and empowering yourself to be educated. And part of that educating might be expanding your team of care.


Okay, I’m going to do one more question and then remember, we have a whole series of these programs.

This came in from Ina: Dr. Michaelis, my mom was recently diagnosed with ET this week; she had a bone marrow biopsy. Maybe you’ve had one, Beth; I’ve had a bunch of them. And please advise why the bone marrow biopsy is needed and what we should expect to take place when we meet with the hem/onc next week to review the results.

Dr. Michaelis:

That’s an excellent question. Essential thrombocythemia can often be – you can suspect it on the basis of the peripheral blood, but you cannot confirm it and clearly know whether or not the condition is essential thrombocythemia or myelofibrosis without examining the bone marrow. So the recommendations, and your doctors followed the standard of care in diagnosis, is to perform a bone marrow biopsy at diagnosis for everyone suspected of having a myeloproliferative neoplasm. It used to be you didn’t need it for PV, but now that’s a part of the recommendations as well.

So, I think they did the right thing by doing the bone marrow biopsy. When you get together with your doctor, you should expect first off for them to clarify exactly what the diagnosis is, and what data has led them to that. The second thing you should ask them is what risks does this pose to my mom; what are the things we need to worry about? Does this make it more likely for her to have bleeding or blood clotting? Is there anything we need to do about that? Is there a reason why she needs to start treatment? And that treatment should be chosen or based on that risk stratification.

So I would say that your conversation should be about what data led to the diagnosis, how sure we are of that diagnosis, and whether or not her risk status require that she be considered for treatment.


Wow, great answer. That really gave me a lot of information. You mentioned Dr. Ruben Mesa, who we all know along the way. He’s going to be with us on a program we’re going to do in August.

So for all of our viewers today, be sure to be signed up with Patient Power so you get our email alerts, and you’ll be kept informed. There are a lot of programs coming up. There’s even an event that’s going to happen I think June 24th in Chicago. So we’re all plugged in. Dr. Michaelis has been with us a number of times; Erin has been with us before.

So we have this sort of community in the MPNs now. I think virtually now, more than ever before; you are not alone. Beth, you saw Esther and I on Facebook Live, you were telling me. We’re all connected, now and Beth is on a program. Beth, I want to wish you well with your PV, and we’ll have you on another program sometime. Thank you for joining us from Oxnard, north of LA today.

Dr. Michaelis:

Good luck, Beth. Thank you.


Thank you both. Thank you.


And Erin, thank you for joining us from Levine Cancer Institute. Please tell Dr. Grunwald hi; give him a hug from me.


I will be happy to.


Thank you for being with us once again, the MPN Hero.


I was in good company.


Oh, thanks. Laura Michaelis from the Medical College of Wisconsin up there where you have either a lot of daylight or not much daylight in Wisconsin, thanks for being with us. And I know you have a cold; feel better, okay?

Dr. Michaelis:

Thank you very much. Thank you.


Okay. Well, we’ve had a great program. Remember, keep informed about our series. The Living Well series is really designed to keep plugging away at the different issues that we face as MPN patients and family members. I want to thank the Patient Empowerment network; this is really their program, produced by Patient Power. We also want to thank the Insight Corporation for their ongoing support.

In Carlsbad California where it’s sunny today, I hope it’s nice weather where you are. I’m Andrew Schorr, and as I like to say: remember, knowledge can be the best medicine of all.

Getting A MPN Specialist’s Opinion

Interview with Olatoyosi Odenike, MD, Associate Professor of Medicine University of Chicago Medical Center and Srdan Verstovsek, MD, PhD, Professor, Department of Leukemia, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center

From the recent MPN Town Meeting, Dr. Verstovsek and Dr. Odenike are asked about why MPN patients should get second, specialist opinions and how it can benefits patients. Check out the full video below to hear from these two MPN experts.

Getting A MPN Specialist’s Opinion? from Patient Empowerment Network on Vimeo.

Cancer Diagnosis – How and Who Do You Tell?

Interview with MPN patients and patient advocates, Lorraine and Karen

At the recent MPN Town Meeting, Andrew Schorr interviews patient advocate, Lorraine about how to explain and communicate with loved ones after a cancer diagnosis. He asks, What do you say? How do you handle it? Who do you tell? What do you tell your kids? Watch the full video below to hear Lorraine and Karen’s answers.

Cancer Diagnosis – How and Who Do You Tell? from Patient Empowerment Network on Vimeo.

What Records Should You Bring For A Second Opinion Appointment?

From the Lung Cancer Town Meeting in September 2016, Janet Freeman-Daily interviews a panel of lung cancer experts about what are the essential records patients should bring to their appointment when getting a second opinion. The panel includes the following experts:

  • Nisha Monhindra, MD Assistant Professor of Medicine, Hematology/Oncology Division, Feinberg School of Medicine Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • D. Ross Camidge, MD, PhD, Director Thoracic Oncology Clinical and Clinical Research Programs University of Colorado Denver
  • David D. Odell, MD, MMSc, Assistant Professor, Thoracic Surgery Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Timothy J. Kruser, MD, Assistant Professor, Radiation Oncology Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Check out the full video below to hear all of the experts advice.

What Records Should Your Bring For A Second Opinion Appointment? from Patient Empowerment Network on Vimeo.

Getting A Second Opinion From A Rural Location?

From a Town Meeting in September 2016, Janet Freeman-Daily interviews a panel of cancer experts about how patients in rural or remote locations can get second or multidisciplinary opinions from larger facilities or academic institutes. The panel includes the following experts:

  • Nisha Monhindra, MD Assistant Professor of Medicine, Hematology/Oncology Division, Feinberg School of Medicine Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • D. Ross Camidge, MD, PhD, Director Thoracic Oncology Clinical and Clinical Research Programs University of Colorado Denver
  • David D. Odell, MD, MMSc, Assistant Professor, Thoracic Surgery Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Timothy J. Kruser, MD, Assistant Professor, Radiation Oncology Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Check out the full video below to hear all the experts advice.


Getting A Second Opinion From A Rural Location? from Patient Empowerment Network on Vimeo.

What is Polycythemia Vera?

Join us in “The Conversation: Polycythemia Vera (PV)” as Dr. Mark Heaney, Dr. Srdan Verstovsek and PV patient, Bob Rosen, discuss the symptoms and treatment options for Polycythemia Vera.

In this first video, participants discuss the biology of PV and the symptoms. Please see other videos from this program here.

What is Polycythemia Vera? from Patient Empowerment Network on Vimeo.

The Need for Doctor/Patient Communication

The Need for Doctor/Patient Communication from Patient Empowerment Network on Vimeo.

Dr. Verstovsek and Dr. Heaney explain that patient education and doctor/patient communication is crucial for good patient outcomes.