Because polycythemia vera (PV) is a slow-growing blood cancer without a cure, you may have the condition for many years. Although PV progresses slowly, there is a risk it can transform into higher-risk conditions, including myelofibrosis (MF).

About 1 in 4 people with polycythemia vera develop MF within 20 years of diagnosis. Keep reading to learn more about how PV can transform into MF and what to look out for.

What Is Myelofibrosis?

In myelofibrosis, your bone marrow becomes damaged and is replaced by fibrosis (scar tissue). Your bone marrow is the soft, spongy substance found in the middle of your bones where blood cells are made. When scar tissue takes over, your bone marrow doesn’t function correctly, so your blood cells can’t develop properly.

Like PV, MF is a type of myeloproliferative neoplasm (MPN) — a group of blood cancers that cause your bone marrow to make too many blood cells.

When MF develops without a known cause, it’s known as primary myelofibrosis. If it develops from another type of myeloproliferative disorder, it’s known as secondary myelofibrosis. If MF develops from PV, it’s also known as post-polycythemia vera myelofibrosis (post-PV MF).

What Are the Symptoms of MF?

Similarly to PV, you may not notice any symptoms of MF in the early stages. As the disease progresses, you may start to notice more symptoms.

Although some symptoms of MF may look similar to those of PV, the cause of the symptoms is different. In PV, your symptoms are caused by too many red blood cells (RBCs). However, in MF, the symptoms are usually caused by a lack or deficiency of blood cells.

The most common symptoms for people with MF are extreme tiredness and an enlarged spleen. When you have too few RBCs, it’s called anemia. If you have anemia, your body can’t get enough oxygen-rich blood, which can cause you to feel extremely tired and weak.

People with MF may have an enlarged spleen — also called splenomegaly. This happens for two reasons — your spleen is trying to produce red blood cells to compensate for bone marrow failure or your spleen is removing damaged RBCs that the defective bone marrow produced. A large spleen, due to too many red blood cells, can cause abdominal pain or discomfort and a feeling of fullness.

MF can affect your body in other ways, such as:

• Bleeding and bruising more easily — MF can cause low platelet count. Because your platelets help your blood clot, having low platelets makes it easier for you to bleed.
• Tumors — MF can cause tumors or blood clumps if your body tries to make up for the lack of blood cells by producing blood cells in parts of your body outside of your bone marrow.
• Portal hypertension (high blood pressure) — This condition can occur if tumors damage the vein that carries blood from your spleen to your liver. The damage can cause increased blood pressure in this vein, resulting in bleeding and stomach swelling.

Other possible symptoms of MF include:

• Unintentional weight loss
• Itching
• More frequent illness
• Joint pain
• Night sweats
• Fever

How Does PV Transform Into MF?

As PV progresses, your condition can start to resemble MF. There are three main stages of PV — the early phase, advancing PV, and the spent phase. In the early phase of PV, you may have no symptoms or mild symptoms. As PV advances, you may start to notice more symptoms of PV or see secondary conditions start to develop.

The spent phase of PV is very similar to MF. In fact, many doctors don’t make a distinction between the spent phase of PV and MF. During this phase, there aren’t any normal blood cells left in your bone marrow. The abnormal cells cause inflammation that leaves scar tissue behind, resulting in bone marrow fibrosis. When this happens, the bone marrow can’t produce blood cells.

Your genes may also influence your risk of getting MF. According to Mayo Clinic, between 60 percent and 65 percent of people with MF have a mutation in their cancer cell genes called Janus kinase 2 (JAK2). JAK2 makes JAK proteins that help regulate how many blood cells your bone marrow makes. About 95 percent of people with PV have JAK2 gene mutations that destroy the normal blood cell production and signal the bone marrow to make too many blood cells.

What Are the Risk Factors for MF?

MF is more common in people over the age of 50. Having PV or another blood disorder called primary thrombocytosis increases your risk of developing MF.

You have an increased risk of developing MF the longer you have PV. After being diagnosed with PV, your risk of MF is about 5 percent after 10 years, 10 percent after 15 years, and 25 percent after 20 years, according to the Journal of Clinical Laboratory Analysis.

You can also develop MF if you don’t have PV. Exposure to ionizing radiation or chemicals, such as benzene or toluene, can increase your risk of MF.

If you’re worried you have a high risk for MF, talk to your doctor.

How Can You Tell if PV Has Transformed Into MF?

If you have PV, it’s important to monitor your symptoms for any changes. MF symptoms can come on gradually, and you may not notice them at first. It’s important to talk to your doctor right away if you notice any new or changing symptoms.

Your doctor will monitor the signs and symptoms of PV regularly (often every three to six months). Blood tests can be used to look for signs that PV is progressing or transforming into MF. Changes in your complete blood count that may indicate PV is transforming into MF include:

• Low levels of RBCs
• White blood cell (WBC) counts that are higher than normal (called leukocytosis) or lower than normal
• Platelet counts that are higher than normal (called thrombocytosis) or lower than normal

Other signs of MF include:

• Abnormal-looking blood cells in your peripheral blood smear
• Changes in your blood chemistry tests, including higher-than-normal levels of uric acid, bilirubin, lactic dehydrogenase, and alkaline phosphatase
• Signs of MF in a bone marrow biopsy (a small sample of your bone filled with marrow for study under a microscope)

Treatment for MF

The treatment options for MF may be different from your treatment for PV, but some treatments can be used for both conditions. Treatment depends on your symptoms, your blood counts, and your age. You may not need treatment right away if you don’t have any symptoms or if your symptoms are mild.

If you have MF, you may need treatments to improve the symptoms of anemia, including:

• Blood transfusions — You may receive blood from a donor to increase your RBCs.
• Androgens — Medications such as danazol (Danocrine) can increase RBC production.
• Immunomodulators — Medications including thalidomide (Thalomid), lenalidomide (Revlimid), and interferon may improve blood cell counts, and they may be combined with corticosteroids.
• Chemotherapy — Drugs including hydroxyurea (Droxia) and cladribine (Leustatin) can be used in people with high RBC counts.

There are three targeted drugs approved by the U.S. Food and Drug Administration (FDA) to treat intermediate or high-risk MF. These drugs work by targeting cells with the JAK2 mutation. They include:

• Ruxolitinib (Jakafi)
• Fedratinib (Inrebic)
• Pacritinib (Vonjo)

If you also have splenomegaly that doesn’t improve with any of the above treatments, you may need a splenectomy (surgery to remove your spleen), or you may need radiation therapy to reduce its size.

A bone marrow transplant may be able to cure MF in some people. This procedure involves replacing your bone marrow with a donor's bone marrow. However, this procedure has life-threatening side effects and isn’t safe for everyone.

You may also be eligible to join a clinical trial researching new treatments for MPNs.

What Is the Outlook for People With MF?

Your prognosis (outlook) is influenced by many factors, including your age, overall health, symptoms, and the presence of specific gene mutations in cancer cells.

In general, MF is an aggressive cancer, and the median survival rate is about six years, according to Cleveland Clinic. This means that half of people with MF live less than six years, while the same number of people live longer than six years.

In contrast, the median survival for people diagnosed with PV at a young age is longer than 35 years.

Talk With Others Who Understand

Find others to connect with at myMPNteam, the social network for people living with myeloproliferative neoplasms and their loved ones. On myMPNteam, more than 3,600 members come together to ask questions, give advice, and share their stories with others who understand life with MPNs.

Has your doctor talked to you about the risk of developing myelofibrosis? Share your experience in the comments below, or start a conversation by posting on your Activities page.