October 27, 2023

Ashley Chan

Patients with myeloproliferative neoplasms (MPNs) may experience a number of symptoms, with fatigue being one of them.

MPNs are types of blood cancer and occur when there is an abnormal change in stem cells within the bone marrow, according to Leukemia and Lymphoma Society. This abnormal change can lead to increased amounts of white blood cells, red blood cells and platelets. The main three types of MPNs are essential thrombocythemia, myelofibrosis and polycythemia vera.

MPN-related fatigue can take a toll on a patient’s quality of life, notably because of the change in the blood’s consistency.

“Fatigue has a profound effect on patients’ quality of life. A lot of people don’t realize that if you have chronic fatigue, especially from MPNs, because your condition is unchecked, then a lot of times it can actually be debilitating,” Patrick Buxton, a clinical nurse coordinator in the hematology department at Fred Hutchinson Cancer Center in Seattle, Washington, said during an interview with CURE®.

“(Patients are) not having the energy to go out and work, participate in family events and just (engage with) life in general. And they just don’t really feel well overall,” Buxton said. “And so, it’s important to monitor these patients’ labs to make sure that they stay within the range for their condition to ensure that they don’t end up developing those symptoms again, because when (a patient’s) blood counts become so high that (their) blood basically becomes a sludge, (they) definitely feel it. And it can cause a whole lot of problems centered around fatigue, but not just fatigue. It can cause a lot of inflammation issues.”

To work through the weight of fatigue, Buxton urged patients to hydrate, eat nutritious food and exercise.

“Especially with MPN, patients maintaining good hydration and adequate nutrition is very important. Because once (patients) kind of get stuck in a downward spiral, it can be very hard to get out,” he noted. “So, making sure that … patients are trying to get a good amount of exercise daily, even if it’s just getting out of bed, pushing (themselves) a little bit each day to try to get that energy going again and making sure that (they) eat and drink enough to keep going.”

Staying hydrated is essential for patients with MPNs, Buxton emphasized.

“Hydration cannot be stressed enough. A lot of people don’t hydrate with water, as I have come to realize, and so there’s been a lot of education patients have like, ‘Oh, I drink all the soda.’

And I’m like, ‘That’s not really helping. You need to drink water, especially when you have this condition, you need to keep on top of things.’”

For patients with MPNs who experience fatigue, Buxton advised them to have open communication with their care teams.

“That line of communication is very important. And even if the patients don’t think it’s important, they know their bodies very well. So, if something is not working right, communicate that to the team,” he said. “And know that it really is a lot of teamwork with the nurses, the patients, the doctors, that the patient is an integral part of the team; without the patient, we wouldn’t be here.

“So, know that (patients are) the center of all of this, and we are here to help, but if (they) don’t report these issues (to us) and just let them be then we won’t know. So, with that information, be a good self-advocate, because that’s how (they’re) going to get better care is being an active participant. Don’t let small things go because sometimes small stuff adds up to something big. And especially with fatigue — patients know their bodies well. So, follow up. Make sure that you are getting the care that you need.”

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October 26, 2023

Darlene Dobkowski, MA

Understanding which of the three types of myeloproliferative neoplasms (MPNs) a patient has can help guide them to receive the appropriate treatment and management of the disease.

Of note, MPNs are a group of rare blood disorders where the bone marrow creates too many blood cells. This can lead a patient to have an imbalance of red blood cells, white blood cells and platelets, all of which can lead to several symptoms. These can include feeling tired, issues with clotting or bleeding and potentially an enlarged spleen.

Unfortunately, the number of patients diagnosed with MDS in the United State each year is not exactly known, according to the American Cancer Society. The organization notes that estimates start at 10,000 and can increase from there. The risk for MDS increases as a patient ages and diagnosis of the disease is uncommon before age 50, according to the American Cancer Society, with most patients diagnosed in their 70s.

Each of the three types of MPNs have their own set of symptoms and management strategies, highlighting the importance of knowing which disease a patient has.

Polycythemia Vera

In patients with polycythemia vera, the bone marrow produces too many red blood cells, which typically carry oxygen throughout the body. This overproduction of red blood cells can thicken a patient’s blood, leading to issues like blood clots and an increased risk for stroke.

The exact cause of polycythemia vera is often not clear, but it is typically related to genetic mutations in the bone marrow cells, particularly in a gene called JAK2. Diagnosis is typically made through blood tests that reveal elevated red blood cell counts, hematocrit levels and the presence of the JAK2 mutation.

Patients with polycythemia vera may experience symptoms like fatigue, headaches and redness or itching of the skin. Treatment for this type of MPN often involves medications and occasionally procedures to reduce the number of red blood cells a patient’s body makes. In particular, treatment for polycythemia vera may include phlebotomy (removing excess blood), medications to reduce blood cell production and management of symptoms and complications.

Essential Thrombocythemia

With essential thrombocythemia, the bone marrow creates too many platelets, which are the cells that help blood clot. Too many platelets can lead patients to experience clotting and bleeding issues. In particular, blood may clot too easily, which can block blood vessels and cause issues like strokes or heart attacks. Paradoxically, patients may also experience bleeding problems because the blood doesn’t clot properly in some cases.

The exact cause of essential thrombocythemia is not well understood, but it is often associated with genetic mutations, particularly in genes like CALR, JAK2 or MPL.

Some patients with essential thrombocythemia may not have any symptoms or they may experience things like headache, dizziness or red spots on their skin.

Patients are recommended to work with their care team to manage the disease and potentially reduce the risk for complications, both of which may be achieved with medications or procedures like plateletpheresis (when platelets are filtered from a patient’s blood through a machine) to control the number of platelets in the blood.

Myelofibrosis

In patients with myelofibrosis, the bone marrow becomes scarred and experiences difficulty in creating enough healthy blood cells, which may lead to fatigue, anemia, an enlarged spleen and an increased risk for infections. Symptoms may also include pain and early satiety, or feeling full even when the patient has not eaten much.

Similar to essential thrombocythemia, myelofibrosis may also be linked to specific genetic mutations like CALR, JAK2 or MPL.

A patient’s care team may manage myelofibrosis with blood transfusions to manage anemia, supportive care to address symptoms, medications to reduce the size of the spleen or, if necessary, a bone marrow transplant.

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October 26, 2023

Alex Biese

Early satiety is one of the symptoms faced by patients with myeloproliferative neoplasms (MPNs) — a set of blood cancers that cause the bone marrow to overproduce red or white blood cells or platelets. Polycythemia vera, essential thrombocythemia and myelofibrosis are all MPNs.

“Early satiety means that you feel full really soon after you start eating,” explained Amanda Smith, a registered nurse at the Huntsman Cancer Institute at the University of Utah. “There are a lot of implications for this. Nutrition is a really big deal, especially when you have a blood disorder or a cancer, so it’s definitely something to be aware of.”

In an interview with Oncology Nursing News, Smith discussed the impact that early satiety can have on patients with MPNs and the role nurses playing in helping patients manage this symptom.

Oncology Nursing News: What kind of impact on quality of life and nutritional intake can this have on patients? And then how can both of those things affect patient outcomes overall?

Smith: If you are not able to eat, it can be really frustrating. Anyone who has ever had a short period of time where they have been unable to eat, knows how run down you can feel, and the lack of energy. You are not getting energy from food as you normally would. And so, it can compound with other things to make you feel just really extra run down. Nutrition is important for our immune systems and it can really have a spiraling effect if we cannot get it under control.

Part of the reason it happens in MPNs is because of splenomegaly, [which] is when your spleen is enlarged. That can happen for a few different reasons, but one of the jobs of the spleen is to filter the blood. When you have an MPN and you have too many platelets or other types of blood cells, then your spleen is — in the simplest terms— working so hard to try and filter all those cells, and it gets too big. Then there is just not room in your abdomen. There’s not enough room in there. That is why it happens.

Patients with MPNs can go through long asymptomatic periods, which is one of the things that makes MPNs really tricky to diagnose and manage. Can this early fullness be a warning sign for patients?

Yes. I know that our providers ask about it every time, so if it’s important enough that they are wanting to know if there have been any changes in that in that area, then yes. Some people can be very stable with this symptom for a long time. As with a lot of things in medicine, the important thing to watch out for is change. You can have a symptom, and it can be stable and may or may not be something to worry about. But if you’ve had an acute change—if something gets a lot worse—it’s definitely something that we would want to know about.

How can nurses help patients manage this issue with things like maximizing their nutritional intake?

The higher calorie foods that you can get down, we would encourage that. We’re also looking at electrolytes a lot, so we’re wanting to make sure those are balanced. High-protein, high-fat types of things, but also just things that you are able to eat. So, it can be really tricky.

A lot of our medications can help shrink the spleen, so medication adherence is huge. Often people feel so much better that they don’t need to be reminded, [but] it’s so critical to stay on the regimen that the doctor prescribes.

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October 26, 2023

By Patrick Daly

According to a single-center, retrospective analysis in Hämostaseologie, myeloproliferative neoplasm (MPN)-associated arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) are frequent, and “while [polycythemia vera (PV)] patients or generally JAK2-mutated MPN patients had a significantly increased risk of such vascular events, this risk was reduced in CALR-mutated MPN patients.”

Lead author Kai Wille, MD, of the Johannes Wesling Medical Center Minden at the University of Bochum in Germany, wrote that patients with BCR–ABL-negative MPN frequently experience morbidity and mortality due to these events; however, few studies have reviewed both MPN-associated ATEs and VTEs across all MPN subtypes.

Uncontrolled MPN at Higher Risk of VTE, ATE

Among 892 patients with MPNs with a median follow-up of 6.6 years (range, 0.0-37.6 years), researchers identified 180 first TEs comprising 105 VTEs and 75 ATEs. The probability of an event by the end of the follow-up period was 36.2%, and the incidence rate for any first TE was 2.43% patient/year.

The most frequent VTE type was deep vein thrombosis with or without pulmonary embolism at a rate of 0.59% patient/year, and the most frequent ATE was stroke at a rate of 0.32% patient/year.

Between the 180 patients with a TE and the 652 without, patients with PV had a significantly increased risk of a TE (hazard ratio [HR], 1.660; 95% CI, 1.206-2.286) compared with other MPN subtypes. Conversely, CALR-mutated MPN had a significantly reduced risk of thromboembolism compared with JAK2-mutated MPN (HR, 0.346; 95% CI, 0.172-0.699).

“In summary, our study shows a significantly increased risk of VTE and ATE (often at “unusual” sites) in MPN patients compared with the healthy population, and this risk seems to be particularly increased in newly diagnosed and/or uncontrolled MPN.” Dr. Wille concluded.

Reference

Wille K, Deventer E, Sadjadian P, et al. Arterial and venous thromboembolic complications in 832 patients with BCR-ABL-negative myeloproliferative neoplasms. Hamostaseologie. 2023. doi:10.1055/a-2159-8767

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October 24, 2023

Pearl Steinzor

Epigenetic changes in myeloproliferative neoplasms (MPNs) have been identified and characterized regarding the effects of aging and therapeutic pathways, according to a recent review. These changes help researchers understand how epigenetic changes affect patients with MPNs and the progression of this rare disease.

In the current study, researchers aimed to review the current knowledge and understanding of epigenetics in patients with MPNs to evaluate and improve management of the disease.

“Reversible epigenetic changes and epigenetic regulation are part of the pathogenesis of MPNs both in the disease development and in progression,” the researchers wrote. “Epigenetic changes in MPN have been investigated with a variety of results.”

Epigenetic changes are reversible modifications to chromatin structure, histone modifications, and DNA methylation, and they are responsible for how genes are either expressed or silenced. Alterations in these structures may result in downstream gene expression changes that may influence the initiation, maintenance, or progression of a malignant cell.

In MPNs, the 3 most common pathogenetic mutations identified were epigenetic regulators: TET2, ASXL1, and DNMT3A, which were present at frequencies above 5% in an unselected MPN patient population. Additionally, EZH2 occurred in approximately 2% of patients with MPN overall and appear particularly important in determining disease progression. The mutations affect the regulation of DNA histone methylation in the hemopoietic stem cell (HSC) compartment. Furthermore, ASXL1, EZH2, IDH1/2, and TET2 were implicated in the progression to fibrotic leukemic transformations and reduced survival.

Additionally, the researchers identified nuclear factor erythroid 2 (NFE2) as a transcription factor that was overexpressed in most patients with MPN. One study found insertions and deletions of NFE2 were described in approximately 2% of patients with MPN. Furthermore, NFE2 mutations were found to be a predictive variable in determining the risk of fibrotic transformation among a large cohort of patients with MPNs with chronic stage disease.

Most studies on DNA methylation have been conducted on a gene-by-gene basis, as well as in comprehensive methylation profiling studies. In a global DNA methylation study of patients with polycythemia vera, essential thrombocythemia, myelofibrosis, including some patients who had transformed to acute myeloid leukemia (AML), MPN samples showed an aberrant methylation pattern compared with control samples. However, samples were similar across the 3 disease types. Furthermore, patients with transformed AML had an increased number of differently methylated regions compared with chronic cases. Therefore, the researchers believe that altered DNA mutations may be associated with the pathogenesis of leukemic transformations in MPNs.

DNA methylation was found to be affected by aging, lifestyle, diet, and disease, so methylation age may be a more accurate describer of disease than chronological age. Studies have found an older methylation age in patients with a higher JAK2V617F allelic burden and in those with a longer disease duration. Patients with polycythemia vera had an older methylation age than predicted, but methylation age was younger than predicted in patients with essential thrombocythemia, which may be attributed to the mutant allele burden.

Additionally, treatment with vorinostat (Zolinza) resulted in younger methylation age in patients with polycythemia vera and an older methylation age in patients with essential thrombocythemia, contributing to an overall trend to normal chronological age. Furthermore, nonresponse to treatment was associated with a younger than predicted methylation age in patients with essential thrombocythemia and an older predicted age in patients with polycythemia vera.

Overall, the researchers believe that these studies show the effect of aging and treatment on the epigenetic changes in MPNs.

“However, there is room for much greater investigation and understanding of epigenetic changes and events involved in progression,” wrote the researchers. “Investigation of the epigenome shows that there are a variety of therapeutic pathways available and that can be explored further leading to targeted therapy.”

Reference

Greenfield G, McMullin MF. Epigenetics in myeloproliferative neoplasms. Front Oncol. 2023;13:1206965. doi:10.3389/fonc.2023.1206965

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October 19, 2023

Patrick Buxton, RN, BSN

Patients with myeloproliferative neoplasms (MPNs) experience a number of symptoms—and fatigue is one of them, explains Patrick Buxton, RN, BSN.

MPNs are types of blood cancer and occurs when there is an abnormal change in stem cells within the bone marrow, according to the Leukemia and Lymphoma Society. This abnormal change can lead to increased amounts of white cells, red cells and platelets. The main three types of MPNs include essential thrombocythemia, myelofibrosis and polycythemia vera.

In an interview, Buxton, who is a clinical nurse coordinator with the hematology department at Fred Hutchinson Cancer Center, spoke with Oncology Nursing News about the symptom of fatigue that patients with MPNs often experience.

Oncology Nursing News: How does fatigue affect a patient’s quality of life?

Buxton: Fatigue has a profound effect on patients’ quality of life. A lot of people don’t realize that if you have chronic fatigue, especially from MPNs, it can actually be debilitating. They [may] not have the energy to go out and work, participate in family events and life in general. And they just don’t really feel well. Just overall.

It is important to monitor these patients’ labs to make sure that they stay within the range for their condition to ensure that they don’t end up developing those symptoms again, because when your blood counts become so high that your blood basically becomes a sludge, you definitely feel it.

Fatigue is a very subjective side effect. How do you try and understand the severity of an individual’s fatigue?

We ask questions of how it is interfering with their day-to-day life. Do they have the energy to go about their day? Do they need to take breaks and several naps? There was once a patient that had fatigue so bad, she could barely get out of bed in the day. We were able to help get her condition under control, and then she was able to get back to her life. It was very hard for her to be in bed because she had 2 small kids.

We were able to kind of dial in her disease and get her started on a medication regimen. She was able to tell with actually her levels of fatigue how her blood counts were doing. She could tell when they were starting to creep up a bit. And we would address her adjust her medication based on labs. But sometimes she would call and say ‘Hey, could I get my labs a couple weeks early? Because I’m noticing my symptoms are starting to come back up a little bit.’ She would be very proactive about trying to keep that under control.

What are some ways a nurse can help patients work through and control fatigue?

A lot of it is to assess how it is affecting their daily life. Sometimes fatigue can also bleed into other things; it is hard to differentiate. Especially with MPNs, [ensuring that] patients maintain good hydration and adequate nutrition is very important. Because once you kind of get stuck in a downward spiral, it can be very hard to get out. Making sure that you educate patients and making sure that they are trying to get a good amount of exercise daily—even if it’s just getting out of bed, pushing yourself a little bit each day to try to get that energy going again, and making sure that you eat and drink enough to keep going [is important].

Hydration cannot be stressed enough, a lot of people don’t hydrate with water, as I have come to realize, and so there’s been a lot of education of patients have like, ‘Oh, I drink all the soda.’ And I’m like, ‘That’s not really helping. You need to drink water, especially when you have this condition, you need to keep on top of things.’

What advice would you offer other nurses who work with patients with MPNs?

Build up that trust with those patients. Have the patient trust that you will take their symptoms seriously when they report them to you.

A lot of patients don’t necessarily like to open up — to say, just the nurse — about their fatigue. But if they are not necessarily within a short distance of your clinic—we have a lot of patients that are in eastern Washington—establishing that line of connection, can be key. Just being like, ‘Hey, let us know, even if you don’t think it’s important,’ ‘Let us know because you don’t know if it’s a sign of something greater, you know your own body.’ And ‘You can tell us when something’s not right, we can always do labs and see. And based on those results, maybe we might do a medication change.’ We might tell you to follow up with your primary care, but we’ll always do something with those lab results.

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