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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October 18, 2023

Alex Biese

Patients with myeloproliferative neoplasms (MPNs) — a group of blood cancers that causes the bone marrow to overproducer red or white blood cells or platelets and which includes polycythemia vera, essential thrombocythemia and myelofibrosis) — are at particular risk for thrombotic and cardiovascular events.

“It’s really a problem for all patients with cancer because it does increase your chances of developing a clot, for example,” said Kim Noonan, nursing and patient care services chief nurse practitioner at the Dana-Farber Cancer Institute in Boston, during a conversation about the risks faced by patients, and the ways in which nurses can help patients prevent cardiovascular and thrombotic events.

However, such risks are of particular concern for patients with MPNs, as literature has shown.

“Clinicians have long recognized an association between MPNs and increased risk for both thrombotic and hemorrhagic complications,” stated the authors of an article published in JACC: CardioOncology. “A recent meta-analysis of 13,436 patients with MPNs showed a pooled prevalence of arterial thrombosis of 16.2% and of hemorrhagic complications of 6.2%. Indeed, cardiovascular events often accompany this cluster of hematologic conditions and contribute significantly to morbidity and mortality.”

Symptoms of a clot or pulmonary embolus include shortness of breath and chest pain, especially following exertion, as well as an elevated or irregular heart rate and an unexplained fever noted Noonan, the co-author of a Journal of Oncology Nursing study on the assessment and prevention of venous thromboembolism and cardiovascular disease among patients with another form of blood cancer, multiple myeloma.

“I’m always thinking about thrombosis first, and then I can relax if I have maybe another explanation for their shortness of breath,” Noonan said. “But we’re always working it up, we really do due diligence to not miss some kind of thrombotic event that’s going on.”

Transcript:
I think when people see me, they just feel like they have to start jogging, because I’m always saying, “You (have) got to move, you have to move, you have to move.” And it’s so, so important. That person that is sedentary is really at a huge risk to the point of where if they have a sedentary lifestyle, we’re thinking maybe that person needs to be on needs to be on anticoagulant therapy right from the beginning, as opposed to just using an aspirin.

We really want people to stay hydrated. We want them to get up and walk around. We want them to be aware of what the symptoms are (and be aware that) they can be doing everything right and still develop a clot because of the medication that they’re on. But I think also, education is essential, (letting a patient know) that you are on a medication that can increase your chances of developing a clot or thrombosis, and (you should) just be aware of what the symptoms are.

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Published on October 9, 2023

By Dr. Suraj D Chiraniya, Clinical Hematologist,  Hemato-oncologist and BMT Physician, HCG Cancer Centre, Borivali

A type of cancer that affects the blood cells. Some common types of blood cancer include leukaemia, lymphoma, and myeloma. Though rare, Myelodysplastic Syndromes (MDS) and Myeloproliferative Neoplasms (MPN) are some other types of blood cancer.

Caused by mutations in DNA within the blood cells, blood cancer results in blood cells behaving abnormally. Treatment, symptoms, and prognosis will vary depending on the type of blood cancer. Further, some types of blood cancer affect children, for which treatment can vary.

Understanding The Various Types Of Blood Cancer

One of the most common types of blood cancer affecting most blood cancer patients is leukaemia, defined as cancer of the blood cells. There are three main categories of blood cells: Red Blood Cells (RBC), White Blood Cells (WBC) and platelets. Leukaemia affects the WBC within the bloodstream and causes them to divide rapidly and eventually crowd out the normal cells. As a result of this, the WBC is unable to perform its function of fighting infections within the human body.

Lymphoma is another type of blood cancer that affects the human immune system. It specifically affects white blood cells called lymphocytes, a vital part of the immune system. Lymphoma can also be called a cancer of the lymphatic system or lymphatic cancer.

In general, there are two main types of lymphoma, namely Hodgkin lymphoma and non-Hodgkin lymphoma, which both affect the blood’s lymphocytes.

The third most common type of blood cancer is myeloma, which affects the blood’s plasma cells. Plasma cells help fight infections in the body, and when a person has myeloma, the body cannot make these antibodies properly. Additionally, abnormal cells multiply in this situation, causing various symptoms.

The majority of the people diagnosed with myeloma are men over the age of 70, although cases of it occurring in young men are also possible.

Who is at risk for blood cancer?

Although there are no specific conditions for blood cancer, the risk can sometimes increase with age. Further, a family history of this disease can also increase the risk.

In addition to the above, the risk of leukaemia can also increase due to the following factors:

•            exposure to radiation

•            treatment with certain chemotherapy drugs

•            a past diagnosis of blood cancer

•            Down syndrome and other genetic syndromes

•            Smoking

Risk factors for lymphoma, on the other hand, include the following:

•            exposure to radiation

•            Epstein-Barr or human T-cell lymphotropic virus

•            HIV, organ transplant, or genetic immune disorders

Some risk factors for myeloma include exposure to radiation, obesity, and other plasma cell diseases.

What are some common signs and symptoms of blood cancers?

Since blood cancer is a chronic condition that progresses slowly, symptoms may not appear until the end stage. While coughing, chest pain, frequent infections, fever and unexplained weight loss can occur in all the types of blood cancer, other symptoms may be specific to the condition.

Some symptoms of leukaemia include fever and lethargy, paleness and shortness of breath due to anaemia and increased bruising and bleeding. When it comes to lymphoma, symptoms may include swollen lymph nodes, fever, night sweats and fatigue and unexplained weight loss. Finally, in the case of myeloma, specific signs may include bone pain, particularly in the back and ribs, weakness, fatigue, and paleness due to anaemia and frequent bacterial infections, such as pneumonia.

Can blood cancer be prevented?

While there is no way to prevent blood cancer completely, certain lifestyle factors can reduce the risk of developing cancer. These include maintaining a healthy diet, exercising regularly, and not indulging in habits like smoking and excessive alcohol consumption.

Preventive health check-ups are highly recommended, especially if a person has a personal or family history of blood cancer, previous sessions of radiation therapy/chemotherapy or radiation exposure. If a person has experienced any symptoms related to blood cancer, it is best to consult an expert, as early diagnosis can ensure the best possible outcome.

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By Nick Paul Taylor

September 18, 2023

Novartis has enlisted artists to help raise awareness of rare blood cancers, commissioning sculptures that portray the 10 key symptoms of the conditions to create a temporary exhibition that will tour the U.K.

The art exhibition is focused on symptoms of myeloproliferative neoplasms (MPN), a group of rare blood cancers that affect around 4,100 people in the U.K. each year. Novartis sells Jakavi for the treatment of MPNs in the U.K., recently securing coverage for one of the three main types of the blood cancer, and wants to spread knowledge that enables more cases to be identified early.

MPNs cause symptoms, such as fatigue, loss of concentration and night sweats, that overlap with other conditions, leading to delayed diagnoses. Novartis wants to bump MPNs up the list of potential causes that patients and physicians consider when they encounter the symptoms.

“More needs to be done to recognize and identify these symptoms early so that people living with the condition can seek help from medical professionals to better manage their symptoms, and those who are undiagnosed can seek a potential diagnosis sooner,” Alisia O’Sullivan, a MPN patient and MPN Voice volunteer, said in a statement.

To support that goal, the Swiss drugmaker has identified 10 key symptoms and commissioned sculptures to represent each of them. Each sculpture is in the shape of the number assigned to the symptom and features art that portrays the symptom. For example, symptom two, inactivity, displays a painting of someone sleeping under a blue sky and symptom three, weight loss, features a quote about being thin.

Novartis worked with MPN Voice and five mural artists from around the U.K. to create the sculptures and began showing them at Westfield, a shopping center in London, last week. The art exhibition will run for one week at Westfield and then go on a tour of U.K. cities.

Encouraging people to consider MPNs as an explanation for the 10 symptoms could support growth products for the condition. Novartis’ sales of Jakavi increased by 11%, rising to $435 million, in the second quarter on the back of demand in emerging markets, Japan and Europe.

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Penny Min

Published September 15, 2023

In blood stem cells with p53 mutations — the so-called “guardian of the genome” — research has uncovered hitherto unrecognized impacts of persistent inflammation on the emergence of cancer.

The protein p53, generated by the gene TP53, is regarded as “the guardian of the genome,” according to research published in Nature Genetics. Apoptosis, a process by which cells “self-destruct” to stop themselves from procreating additional damaged cells, is triggered when p53 is activated. However, mutations can make p53 ineffective, which allows injured cells to continue dividing unchecked.

As many as 50% to 60% of human malignancies have a TP53 mutation, which can result in cancer development. Hematopoietic stem cells (HSCs) with TP53 mutations have been associated with acute myeloid leukemia (AML), an aggressive kind of blood cancer.

By creating all different types of blood cells, they are in charge of preserving a healthy blood system. The processes behind how these mutant HSCs multiply to produce cancer were largely unknown. In the current study, researchers from the University of Oxford examined how chronic inflammation affects TP53-mutant HSCs in cancer development.

The study team used TARGET-seq, a single-cell method, to examine the impact of the mutation. This enabled them to use cells provided by individuals with myeloproliferative neoplasms, a condition that predisposes them to leukemia, to explore how TP53 mutations in HSCs impact cancer progression.

What did the results entail?

Researchers discovered that cells from individuals with TP53 mutations exhibited higher levels of inflammation-related gene activation. They established, using laboratory mice, that these mutant cells multiplied when the animals were exposed to inflammatory stimuli.

Additionally, compared to healthy HSCs, the mutant HSCs generated fewer white blood cells and were more resistant to cell death, which is normally brought on by inflammation. This indicates that compared to non-mutant HSCs, the mutated HSCs were better able to grow when exposed to inflammation and were more “fit” to survive.

The inability of TP53-mutated cells to effectively repair mistakes in their genetic coding when subjected to inflammation may exacerbate this impact and aid in cancer growth.

“Overall, these findings offer valuable insights into how genetic defects and inflammation interact in the development of blood cancer.”

– Co-first author Alba Rodriguez-Meira

Additionally, she continues that this research may lead to novel approaches for TP53-mutant leukemia therapy and other cancer types, improving results for cancer patients.

The connection between inflammation and genetic evolution in cancer has broad implications, says senior author Adam Mead. The challenge is to figure out how scientists might intervene in this process to treat or prevent the inflammation linked to cancer progression more effectively.

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Sep 8, 2023

September 6, 2023

Vicki Moore, PhD

A review article published in the Journal of Cellular and Molecular Medicine details recent progress in the development of antibodies targeting mutated calreticulin, aimed at providing a novel therapy option for myeloproliferative neoplasms (MPN). The review was authored by Frederike Kramer, PhD, and Ann Mullally, MD, of Harvard Medical School in Boston, Massachusetts.

Calreticulin is encoded by the CALR gene and alterations in this gene are common drivers of the development of MPN. In most cases, these occur as 1 of 2 mutations in exon 9 of this gene, as Kramer and Mullally explained in their review. Approximately half of the patients with a CALR mutation have a 52-bp deletion, whereas approximately 30% of patients with a CALR mutation have an insertion of 5 bp in the sequence of this gene.

These types of mutations in CALR lead to a frameshift that causes formation of an altered C-terminus in calreticulin, resulting in the absence of an endoplasmic reticulum retention signal. The altered calreticulin is thus directed toward the cell’s surface, where it shows aberrant binding to the thrombopoietin receptor protein (MPL), with the interaction ultimately contributing to activation of the JAK-STAT signaling pathway and cell transformation.

Currently, patients with MPN are often treated with cytoreductive therapies. Allogeneic stem cell transplantation can be curative for patients with CALR-mutated MPN, but this approach carries risks of morbidity and mortality.

However, the interaction of altered calreticulin and MPL provides a possible substrate for a potential targeted treatment approach. Monoclonal antibodies (mAbs) directed at altered calreticulin have been the subject of research, and a range of studies have generated results indicating this may be a possible approach to treatment of CALR-mutated MPN.

Additional immunological approaches to treating MPN that have been under investigation involve peptide vaccination directed at altered calreticulin and T cell-directed targeting agents. Antibody-drug conjugates could also present a possible avenue of treatment, with these agents potentially binding to both mutated calreticulin and MPL within a complex, rather than binding to mutated calreticulin that has simply been secreted.

“Recent advances in identifying the mechanisms by which mutant calreticulin causes MPN paved the path for immunological targeting of CALR-mutant MPN cells, and specific mutant calreticulin targeting mAbs have been developed and found to be efficacious in preclinical mouse models,” the authors wrote in their report, also noting safety and efficacy with these agents have not yet been evaluated in this patient population.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

Reference

Kramer F, Mullally A. Antibody targeting of mutant calreticulin in myeloproliferative neoplasms. J Cell Mol Med. Published online August 7, 2023. doi:10.1111/jcmm.17896

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