Myeloproliferative Neoplasms

What are myeloproliferative neoplasms (MPN)?

Myeloproliferative neoplasms (MPNs) are rare, potentially life-threatening blood cancers that happen when your bone marrow makes too many blood cells. Blood cells include red blood cells, white blood cells and platelets. They’re made in the spongy tissue inside of your bones. With a myeloproliferative neoplasm, something goes wrong in the blood cell production process.

Myeloproliferative (pronounced “MY-eh-loh-proh-LIH-feh-ruh-tiv) neoplasms develop very slowly, so people may have them for years before noticing symptoms. Myeloproliferative neoplasms are also called chronic myeloproliferative neoplasms or myeloproliferative disorders. Chronic means that a condition is long-term. Rarely, a myeloproliferative neoplasm may turn into a more serious disease.

There are treatments that ease symptoms and reduce the risk of a myeloproliferative neoplasm developing into a more serious disease.

What are the types of myeloproliferative neoplasms?

Depending on the type of myeloproliferative neoplasm, your bone marrow may make too many red blood cells, white blood cells, platelets or a combination of cell types. The cells often behave differently from healthy blood cells.

Who do myeloproliferative neoplasms affect?

Your age and sex are the most significant predictors of how likely you are to have a myeloproliferative neoplasm.

• Age: Myeloproliferative neoplasms affect multiple age groups, but they’re most common in people in their 50s, 60s or older.
• Sex: Polycythemia vera is generally more common in men and people assigned male at birth. Essential thrombocythemia is more common in women and people assigned female at birth. The remainder of the myeloproliferative neoplasms occur equally in both sexes.

How do myeloproliferative neoplasms affect my body?

These blood diseases happen when your bone marrow makes more of a certain blood cell type than your body can use. The impact on your body varies based on the blood cell type affected. For example, one type of myeloproliferative neoplasm increases your risk of heart attack or stroke. Another type may cause anemia.

To understand these rare diseases, it may help to have some information about your bone marrow and blood cell production. All blood cells start as stem cells in your bone marrow. Your bone marrow is soft, sponge-like tissue in the center of your bones. It makes cells that may become myeloid stem cells or lymphoid stem cells.

Lymphoid stem cells become white blood cells that help fight infection. Myeloid stem cells can become red blood cells that carry oxygen throughout your body, white blood cells or platelets, which prevent excessive bleeding.

Like all cells, stem cells take instruction from genes that help dictate cells’ form and function. Normally, your bone marrow makes stem cells that divide and multiply as needed. These stem cells follow directions from genes that help regulate cell development.

When these genes mutate, they send new instructions to certain stem cells, telling the cells to keep on dividing and multiplying. Eventually, these stem cells become mature blood cells that pile up in your bone marrow or bloodstream, affecting blood flow. Blocked blood flow can cause serious medical conditions.

What are common myeloproliferative neoplasms?

The three most common types are polycythemia vera, essential thrombocythemia and primary myelofibrosis.

Polycythemia vera

This is the most common myeloproliferative neoplasm. It makes your bone marrow produce too many red blood cells. The excess red blood cells make your blood thick, so blood moves more slowly through your bloodstream. People with polycythemia vera are likely to develop blood clots that may cause heart attack and stroke. Very rarely, polycythemia vera may progress or become serious blood diseases, including acute leukemia.

Myelofibrosis

This is the most aggressive myeloproliferative neoplasm. In myelofibrosis, your bone marrow produces abnormal stem cells that become inflamed and make scar tissue. Over time, your bone marrow fills up with scar tissue. The scar tissue keeps your bone marrow from making enough red blood cells to carry oxygen throughout your body, and you may develop anemia. Your bone marrow also falls behind on platelet production. Platelets help to slow and stop excessive bleeding. Some people with myelofibrosis will develop acute myeloid leukemia.

Essential thrombocythemia

Essential thrombocythemia happens when your bone marrow makes too many platelets. If a blood vessel ruptures, platelets make blood clots that slow or stop bleeding. In essential thrombocythemia, your bone marrow makes platelets even when there’s no need for them. These excess platelets become blood clots that increase your risk of having a heart attack or a stroke. Like other myeloproliferative neoplasms, essential thrombocythemia symptoms develop very slowly. Most people learn they have this disease when routine blood tests show high platelet levels. Some people with essential thrombocythemia may develop leukemia.

What are other types of myeloproliferative neoplasms?

Other MPN types include:

• Chronic eosinophilic leukemia (CEL) involves the overproduction of white blood cells called eosinophils. Usually, it progresses slowly. In rare cases, CEL can become a serious form of cancer called acute myeloid leukemia (AML). CEL is also called hypereosinophilic syndrome.
• Chronic myelogenous leukemia (CML) involves an overproduction of white blood cells called granulocytes. These cells accumulate, making it harder for your bone marrow to make other blood cells your body needs.
• Chronic neutrophilic leukemia (CNL) involves an overproduction of white blood cells called neutrophils.
• Myeloproliferative neoplasm, unclassifiable (MPN-U), is a type of myeloproliferative neoplasm that doesn’t fit into the other categories. It may involve an overproduction of various blood cell types, including white blood cells, red blood cells or platelets.

What are myeloproliferative neoplasm symptoms?

You likely won’t notice symptoms in the early stages. As your condition progresses, you may notice signs of an enlarged spleen (splenomegaly). Splenomegaly feels like fullness, pressure or discomfort below your ribs on your left side, where your spleen is located. While splenomegaly is a common symptom of most myeloproliferative neoplasms, it’s a less common symptom of essential thrombocytopenia.

Other symptoms depend on the specific myeloproliferative neoplasm.

Chronic eosinophilic leukemia

The most common symptom is a rash. You may also feel tired and feverish. Other symptoms depend on what body parts are affected by your high eosinophil levels.

Chronic myelogenous leukemia and chronic neutrophilic leukemia

Symptoms may include:

• Bone pain.
• Night sweats.
• Fever and fatigue.
• Bruising easily.
• Loss of appetite and weight loss.

Essential thrombocythemia

Symptoms may include:

• Bruising easily.
• Unexplained bruising or bleeding from your nose, mouth and gums.
• Bleeding from your stomach or intestines.
• Blood in your pee.

Polycythemia vera

Symptoms may include:

• Headaches.
• Dizziness.
• Fatigue.
• Blurred or double vision.

Primary myelofibrosis

You may experience symptoms of anemia (fatigue, weakness, shortness of breath). Other signs and symptoms may include:

• Pale skin.
• Night sweats.
• Fevers.
• Itchy skin.
• Abdominal fullness or filling up right away when you eat (early satiety).
• Weight loss.
• Bone pain.

What causes myeloproliferative neoplasms?

All myeloproliferative neoplasms are acquired genetic disorders. This means you can’t inherit these diseases from your biological parents. These diseases happen when genes that regulate cell growth mutate or change and your blood cell development goes wrong.

Medical researchers have made the following discoveries about the genetic mutations that cause myeloproliferative neoplasms:

• Mutations associated with Janus kinases (JAK): Polycythemia vera, primary myelofibrosis and essential thrombocythemia often involve genetic mutations associated with a protein called Janus kinase 2 (JAK2). The mutation may cause cells to multiply out of control.
• Mutations associated with the MPL gene or CALR gene: People with essential thrombocythemia and primary myelofibrosis often have mutations in their MPL gene or CALR gene.
• Chromosome errors: People with chronic myelogenous leukemia (CML) have a specific error involving their chromosomes. A chromosome is a structure that contains genes. With CML, a piece of one chromosome swaps places with another chromosome, forming the “Philadelphia chromosome.”

These discoveries don’t clarify what causes genetic changes to take place. Still, they help healthcare providers make a diagnosis and develop treatments targeting genetic mutations.

What are the risk factors associated with myeloproliferative neoplasms?

Family history, age and sex may increase the risk of developing MPN.

Researchers have also found links between myeloproliferative neoplasms and certain toxins and radiation exposure. Some studies show people exposed to high levels of radiation and certain toxins like benzene have an increased risk of developing myeloproliferative neoplasms, like polycythemia vera, primary myelofibrosis and chronic myelogenous leukemia.

How are myeloproliferative neoplasms diagnosed?

A healthcare provider will collect a detailed medical history and perform a physical exam to check for signs and symptoms of a myeloproliferative neoplasm. They’ll run tests on your blood and bone marrow to make a diagnosis.

• Complete blood count (CBC): This test measures all blood cell levels. In essential thrombocythemia, providers evaluate platelet levels. In polycythemia vera, they look for increased hemoglobin — the protein in red blood cells — as well as white blood cells and platelets.
• Peripheral blood smear (PBS): This test can show abnormal cell shapes that may indicate a condition. Blood chemistry tests can detail how much of a specific type of chemical is in your blood (proteins, enzymes, glucose, etc.). These numbers provide clues about how your organs are functioning, which may suggest a myeloproliferative neoplasm.
• Bone marrow biopsy: Your provider may do bone marrow aspiration or bone marrow biopsy. In this test, they remove a sample of bone marrow to check your blood cells. Then, medical pathologists examine blood cells and tissue under a microscope, looking for differences between normal and abnormal cells. They’ll see if you have an unusual number of stem cells. They’ll also look for changes in chromosomes and other signs of genetic mutations that may indicate you have a specific type of myeloproliferative neoplasm.
• Genetic testing:Providers may analyze your blood cells, looking for changes in the genes that may affect blood cell production.

Can healthcare providers cure myeloproliferative neoplasms?

Allogeneic stem cell transplantation is the only known cure for these diseases. Unfortunately, many people can’t have stem cell transplantations because they may not be able to go through the strenuous stem cell transplant process.

Your healthcare provider will provide treatments that manage your condition by reducing the number of blood cells, providing symptom relief and preventing complications. There are some treatments that can lead to remissions. MPN treatments vary by type:

• Chronic eosinophilic leukemia: Your provider will work to reduce your eosinophil levels with chemotherapy, corticosteroids or immunotherapy.
• Chronic myelogenous leukemia: The most common treatment is targeted therapy that prevents cells from multiplying out of control. Other treatments include chemotherapy, immunotherapy, radiation therapy and stem cell transplants.
• Chronic neutrophilic leukemia: Treatments may include chemotherapy, immunotherapy and stem cell transplants.
• Essential thrombocythemia: If you don’t have symptoms, your provider may choose to monitor your condition closely instead of prescribing treatments. If you have symptoms, you may need to take a treatment that prevents cells from multiplying out of control. You may need to take medicine to reduce your risk of blood clots or to prevent your bone marrow from making too many platelets.
• Polycythemia vera: Phlebotomy is the most common procedure to treat polycythemia vera. Your healthcare provider will regularly remove blood (like a blood draw) to reduce your blood volume and remove excess red blood cells. If you have symptoms, you may have targeted therapy that prevents cells from multiplying out of control. You may also take medicine to reduce your risk of blood clots (like aspirin) or to reduce your number of red blood cells.
• Primary myelofibrosis: Your provider may decide to monitor your condition closely if you aren’t experiencing symptoms. Treatments may include procedures or drugs to treat anemia. For example, you may need a blood transfusion if your bone marrow isn’t making enough red blood cells. You may take medicines that stimulate your bone marrow to produce more blood cells. Other treatments may include targeted therapy, chemotherapy, immunotherapy, radiation therapy and stem cell transplant.

How long can I expect to live if I have a myeloproliferative neoplasm?

Experiences vary based on many factors, including the type of myeloproliferative neoplasm, how early your condition was diagnosed and how you respond to treatment. With careful monitoring and treatment, many people live for several years. There’s no single prognosis or expected outcome for these conditions. In general, people diagnosed with MPN are alive five years later. Survival rates for specific MPNs are:

• Chronic myelogenous leukemia: The effectiveness of new targeted therapies has significantly increased the survival rate associated with CML. The five-year survival rate for CML is 90%.
• Chronic neutrophilic leukemia and polycythemia vera: With careful management, many people live 20 years, on average, following their diagnosis.
• Essential thrombocythemia: Many people live many years with essential thrombocythemia when they take medications that prevent life-threatening complications, like blood clots.
• Primary myelofibrosis: Most people with primary myelofibrosis are still alive five to 10 years after a diagnosis.

If you have this condition, ask your healthcare provider to explain your prognosis. They know all the factors that affect prognosis. Just as important, they know you, including risk factors like your age and overall health that affect your prognosis.

Are these diseases fatal?

On their own, these aren’t fatal diseases, but some may cause life-threatening conditions such as heart attack or stroke.

What questions should I ask my doctor?

Myeloproliferative neoplasms are a complex group of diseases with multiple treatment options that sometimes cause side effects. Similarly, various complications can arise depending on your condition. It’s important to know what signs or symptoms you should be aware of. Talk to your provider so you understand your diagnosis and can make care decisions.

Questions may include:

• What’s the goal of treatment (remission, improving symptoms, preventing complications, etc.)?
• What are my treatment options?
• What are the potential side effects of treatment?
• How often will I need treatment for my condition?
• How often will I need imaging or blood work to monitor my condition?
• What signs or symptoms will let me know that my condition is improving or worsening?
• What signs or symptoms will alert me of a complication?
• Which complications require emergency medical attention?
• What’s my likely prognosis?
• What lifestyle changes would you recommend so that I’m managing my condition and treatment side effects?

How do I take care of myself?

It can be confusing living with a myeloproliferative neoplasm. You may feel fine and wonder if there’s anything you can do to prevent symptoms. If you’re receiving treatment, you may need help managing treatment side effects and symptoms. Either way, you’ll likely be living with your disease for years to come. Here are some suggestions that may help:

• Understand your health situation:Many myeloproliferative neoplasm symptoms resemble less serious conditions. Some symptoms may be signs of serious medical complications. It may be hard to tell the difference and you may worry you’re missing important clues about your health. Ask your healthcare provider to explain how the disease may affect you. Knowing what to expect may help you feel more confident about your situation.
• Manage your stress:It can be stressful living with a long-term illness. If you’re feeling anxious about your situation, talk to your provider about your concerns. They’ll explain what they’re doing to help you now and what they’ll do to help you in the future.
• Eat balanced healthy meals:Eating well will give you the energy to manage your condition. If you need help developing healthy eating habits, ask to speak with a nutritionist.
• Get some exercise:Exercise is a great way to manage stress.
• Find some support: Myeloproliferative neoplasms are rare diseases. Support groups may be a way to connect with and talk to people who know what you’re going through.

When should I see my healthcare provider?

If you have a myeloproliferative neoplasm but don’t have symptoms, contact your healthcare provider if you notice changes in your body that may indicate you’re developing symptoms.

A note from Cleveland Clinic

Myeloproliferative neoplasms (MPNs) are rare, potentially life-threatening blood cancers that happen when your bone marrow makes too many blood cells. In some ways, myeloproliferative neoplasms are mysterious diseases. Researchers know myeloproliferative neoplasms involve abnormal blood cell growth. They know these are genetic disorders, but they don’t know what triggers the genetic mutations that cause MPNs. They’re rare diseases so many people don’t know what it’s like to live with a myeloproliferative neoplasm. But healthcare providers and researchers are learning more about myeloproliferative neoplasms, particularly more effective ways to manage symptoms and reduce the risk of serious medical complications.