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What Is Cytoreductive Therapy in MPNs?

Posted on December 29, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Jessica Wolpert

Myeloproliferative neoplasms (MPNs) are bone marrow and blood cancers in which genetic mutations cause abnormal blood cell production. There are three classic MPNs: With polycythemia vera (PV), you produce too many red blood cells. With essential thrombocythemia (ET), you produce too many platelets. If you have primary myelofibrosis (MF), scarring in your bone marrow causes the production of red and white blood cells with abnormalities. These excess and deformed blood cells can create serious complications, such as blood clots. Other MPNs include chronic myeloid leukemia and mastocytosis.

Some people with MPNs don’t experience symptoms and aren’t at high risk of experiencing complications. For these people, watchful waiting may be enough. This means not starting any treatment, but carefully monitoring the disease over time for any changes or worsening.

However, for people with certain risk factors, medical treatment for MPNs might be necessary. These risk factors include:

  • Being over 60 years old
  • Symptoms caused by an MPN (like weight loss or bone pain)
  • Large spleen
  • High blood count
  • Other health conditions, such as diabetes or hypertension (high blood pressure)

There are several treatment options available for MPNs. One of these treatments is cytoreductive therapy.

What Is Cytoreductive Therapy?

According to Dr. Andrew Kukyendall, assistant professor of oncologic sciences at the University of South Florida, physicians usually use the term “cytoreductive therapy” to refer to certain medications that are used to treat MPNs. These medications work by reducing levels of blood cells. Other treatments technically remove blood cells, such as phlebotomy — in which blood is removed from the body, similar to blood donation — and apheresis, in which blood is filtered for excess cells and returned to the body. These treatments are usually not called cytoreductive therapy.

What Are Reasons To Start Cytoreductive Therapy?

Not everyone with an MPN will need to undergo cytoreductive therapy. In PV and ET, people who are considered low-risk (younger people who have never had a blood clot) may be treated with aspirin and monitoring only. People with MF who are low-risk and symptom-free also may not need cytoreductive therapy.

Reasons to start taking cytoreductive medications include:

  • Experiencing worsening symptoms (bone pain, fever, weight loss, etc)
  • Having too many platelets or white blood cells
  • Having an enlarged spleen (splenomegaly)
  • Needing frequent phlebotomy (blood draws) or ongoing phlebotomy
  • Having too many blood clots
  • Being unable to form blood clots (easy bleeding)

Your health care team will help you decide when and if cytoreductive therapies are right for your condition.

Medications for Cytoreductive Therapy

According to Dr. Kukyendall, the most common medications used in cytoreductive therapy are:

  • Interferon therapies
  • Hydroxyurea (or hydroxycarbamide), sold as Droxia, Hydrea, and Siklos
  • Ruxolitinib, sold as Jakafi
  • Anagrelide, sold as Agrylin

Interferons

Interferons are proteins that naturally occur in the body, but they can also be lab-made. There are many different formulations of interferons, made by several different companies, used for immunotherapy. They work by triggering the immune system to break down unwanted cells.

Interferons are used to treat viruses and cancers, including MPNs (especially ET and PV). Older versions of interferons had many undesirable side effects, including severe flu-like symptoms and too-low blood cell counts. However, newer formulations are proving safer and more effective.

Research and clinical trials are still ongoing to find the best formulations of these drugs. They are currently recommended as first-line treatments in young people and those who are pregnant. Interferon is given as an injection.

Hydroxyurea

Hydroxyurea decreases the number of blood cells that your bone marrow produces. Because it affects all types of blood cells, it is generally useful for all types of MPNs. Available in capsule form, hydroxyurea is a chemotherapy medication, but it is usually taken at low doses to treat MPNs. Its side effects are generally mild.

Because hydroxyurea reduces the production of all blood cells, it can cause too-low levels of some blood cell types. You can develop anemia (low levels of red blood cells). They also can increase your risk of infection, due to low levels of white blood cells. Your platelet levels can drop too far, causing nosebleeds, bleeding gums, and easy bruising. The medication is not recommended for people who are pregnant.

Other side effects of hydroxyurea include diarrhea, constipation, and darkened skin. Hydroxyurea can increase your risk of developing skin cancer, so avoid sun exposure whenever possible and wear a strong sunscreen when you do go out.

Ruxolitinib

Ruxolitinib is a type of drug called a Janus kinase (JAK) inhibitor. It blocks a protein that the body uses to signal cells to grow. Ruxolitinib is approved by the U.S. Food and Drug Administration (FDA) to treat certain types of myelofibrosis, as well as PV that hasn’t responded to hydroxyurea. It’s also approved for people who can’t tolerate hydroxyurea use. Ruxolitinib is taken in tablet form.

As with hydroxyurea, ruxolitinib can cause too-low levels of red and white blood cells, as well as platelets. Ruxolitinib is associated with a higher risk of infections in general. Taking ruxolitinib can cause symptoms of certain dormant diseases — such as herpes zoster infection, hepatitis, and tuberculosis — to reappear. For example, people taking ruxolitinib may experience a painful rash and blisters as part of shingles, a condition that occurs when the herpes zoster virus (more commonly known as the chickenpox virus) is reactivated. If you have had or think you have had one of these conditions, talk to your doctor before starting ruxolitinib .

Other side effects of ruxolitinib include high cholesterol levels, dizziness, headache, and weight gain. It can also cause extra stomach gas and flatulence.

Fedratinib, sold as Inrebic, is the most recent JAK inhibitor drug approved by the FDA for treating myelofibrosis.

Anagrelide

Taken in capsule form, anagrelide is the most specific form of cytoreductive treatment. It lowers platelet counts by reducing the production of megakaryocytes, the cells that go on to produce platelets. It does not affect red and white blood cell numbers. “Anagrelide is pretty much a platelets-specific drug, so it doesn’t do what we’d like it to do in polycythemia vera, but it does lower the platelet counts in ET,” said Dr. Kukyendall.

Common side effects of anagrelide include headaches, fluid retention (edema), and diarrhea.

Monitoring Cytoreductive Therapy

It is important to stay in touch with your treatment team regularly during cytoreductive therapy. Depending on your condition, you may need to follow up for regular tests and blood work every three to four months — or more frequently if you are having problems, like worsening symptoms, blood clots, bleeding, or infections.

If you are having side effects from the medication or it does not seem to be working, your specialist may decide to try another medication or treatment. It is important to remember that everyone with an MPN will experience unique symptoms and responses to therapy.

Connect With Others Who Understand

On myMPNteam, more than 1,900 people living with MPNs come together to ask questions, give advice, and share their stories with others who understand life with the condition.

Share your MPN journey in the comments below, or start a conversation by posting on your Activities page.

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Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Jessica Wolpert works to empower patients through the creation of content that illuminates treatments' effects on the everyday lives of people with chronic conditions. Learn more about her here.

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