Primary myelofibrosis facts for kids

Primary myelofibrosis (PMF) is a rare type of blood cancer that affects the bone marrow. The bone marrow is like a factory that makes all your blood cells. In PMF, the bone marrow becomes scarred and stiff. This scarring is called fibrosis. Because of this scarring, the bone marrow can't make enough healthy blood cells, like red blood cells, white blood cells, and platelets.

This condition is part of a group of cancers called myeloproliferative neoplasms. These cancers happen when certain cells in the bone marrow grow too much because of changes (called mutations) in their genes. The most common genes involved in PMF are JAK2, CALR, or MPL.

People with PMF might feel tired, have fevers, night sweats, or bone pain. Their spleen might also get bigger, which is called splenomegaly. They can also have a higher risk of infections or bleeding.

What are the signs and symptoms?

The main problem in primary myelofibrosis is the scarring of the bone marrow. But it often comes with other signs and symptoms:

• Feeling full in the belly: This is often because the spleen gets much larger (splenomegaly).
• Bone pain: Aching or discomfort in the bones.
• Easy bruising and bleeding: This happens because there aren't enough platelets, which help blood clot.
• Weight loss and tiredness: People might lose their appetite, lose weight, and feel very tired.
• Enlarged liver and spleen: Both organs can become bigger.
• Fevers and chills: Feeling hot or cold without a clear reason.
• Gout: A type of arthritis caused by high levels of uric acid in the blood.
• More infections: The body might have trouble fighting off sicknesses like pneumonia.
• Pale skin and shortness of breath: These are signs of anemia, which means not enough red blood cells.
• Skin problems: In rare cases, bumps or nodules can appear on the skin.

What causes primary myelofibrosis?

Primary myelofibrosis is almost always caused by a change (a mutation) in certain genes within the blood-forming cells in the bone marrow. About 9 out of 10 people with PMF have a mutation in one of these genes: JAK2, CALR, or MPL. About 10% of people do not have mutations in these three genes.

These gene changes are not only found in PMF. They can also be seen in other similar blood conditions like polycythemia vera and essential thrombocythemia.

The JAK2 gene mutation is found in about half of people with PMF. This mutation makes the JAK2 protein too active. This protein is important for telling blood cells when to grow and multiply. When it's too active, it causes the bone marrow to make too many cells, which can lead to the problems seen in PMF.

The MPL gene also codes for a protein that helps make platelets. A mutation in this gene can make the protein always "on," even when it shouldn't be. This leads to too many megakaryocytes (cells that make platelets) in the bone marrow. These abnormal cells then release substances that cause the bone marrow to scar.

How does primary myelofibrosis affect the body?

Myelofibrosis is a condition where the bone marrow, which normally makes blood cells, gets scarred. This scarring means the bone marrow can't do its job properly. As a result, the body tries to make blood cells in other places, like the liver and spleen. This is called extramedullary hematopoiesis.

When the liver and spleen try to make blood cells, they often get much bigger. An enlarged spleen is called splenomegaly, and an enlarged liver is called hepatomegaly. A very large spleen can also destroy blood cells, leading to low numbers of platelets and red blood cells.

Sometimes, myelofibrosis can develop in people who first had other blood disorders, like polycythemia vera.

Where does blood cell formation happen?

The main place where blood cells are made outside the bone marrow in PMF is the spleen. The spleen can become very large, sometimes weighing as much as 4 kilograms (about 9 pounds)! Inside the spleen, doctors can see immature red blood cells, white blood cells, and cells that make platelets. These platelet-making cells are thought to cause the scarring in the bone marrow. The liver also often gets bigger and tries to make blood cells.

How is primary myelofibrosis diagnosed?

This condition usually develops slowly and is mostly seen in people over 50 years old.

Doctors diagnose PMF by taking a small sample of your bone marrow (a bone marrow biopsy). They look at the sample under a microscope to see how much scarring (fibrosis) there is.

During a physical exam, a doctor might feel if your spleen or liver are enlarged.

Blood tests are also important. At first, the blood might look similar to other blood conditions. Most people with PMF have anemia, meaning they don't have enough red blood cells. Over time, they might also develop thrombocytopenia, which is a low number of platelets.

When a blood sample is viewed under a microscope, it can look very unusual. There might be a reduction in all types of blood cells (red, white, and platelets). Red blood cells might have strange shapes, like teardrop-shaped cells. Immature red blood cells, white cells, and large platelet-making cells might also be seen in the blood.

Sometimes, when doctors try to take a bone marrow sample, they get a "dry tap." This means no liquid bone marrow comes out because it has been replaced by tough, scarred tissue.

How is primary myelofibrosis treated?

The only known treatment that can cure primary myelofibrosis is an allogeneic stem cell transplant. However, this treatment has serious risks.

Other treatments mainly help manage the symptoms and improve quality of life. These can include:

• Taking folic acid or allopurinol.
• Getting regular blood transfusions to help with anemia.
• Medications like dexamethasone, alpha-interferon, or hydroxyurea.
• Some newer drugs like lenalidomide and thalidomide may also be used.

If the spleen becomes very large and causes problems, doctors might consider removing it with surgery (called a splenectomy). However, this is a high-risk surgery.

In recent years, new medications have been approved to treat PMF:

• In 2011, the U.S. Food and Drug Administration (FDA) approved ruxolitinib (Jakafi). This medicine helps reduce the size of the spleen and improves symptoms.
• In 2019, the FDA approved fedratinib (Inrebic) for adults with certain types of myelofibrosis.
• In 2022, the FDA approved pacritinib (Vonjo) for adults with PMF who have very low platelet levels.

History of primary myelofibrosis

The condition now known as myelofibrosis was first described in 1879 by a doctor named Gustav Heuck.

In 1951, William Dameshek described it as a "myeloproliferative" condition, meaning it involves the overgrowth of certain cells in the bone marrow.

Over the years, the name of the disease changed. It was once called myelofibrosis with myeloid metaplasia or agnogenic myeloid metaplasia. The World Health Organization (WHO) used the name chronic idiopathic myelofibrosis until 2008, when it officially became primary myelofibrosis.

In 2016, the WHO further refined its classification, recognizing Prefibrotic primary myelofibrosis as a separate condition that can sometimes progress to overt PMF.

See also

In Spanish: Mielofibrosis con metaplasia mieloide para niños