Myelofibrosis

Myelofibrosis is a rare type of bone marrow cancer where the bone marrow, which normally makes blood cells, becomes scarred and cannot produce healthy blood cells. This leads to a shortage of normal blood cells and can cause various symptoms, including fatigue and an enlarged spleen. It is a chronic condition that requires ongoing management.

What is Myelofibrosis?

Myelofibrosis is a rare type of chronic blood cancer that affects the bone marrow, the spongy tissue inside your bones where blood cells are made. In this condition, the bone marrow develops scar tissue (fibrosis), which prevents it from producing enough healthy red blood cells, white blood cells, and platelets.

Normally, your bone marrow contains stem cells that mature into all types of blood cells your body needs. With myelofibrosis, these stem cells become abnormal. They start to produce too many immature blood cells, which then cause scarring in the bone marrow. This scarring makes it difficult for the bone marrow to function properly. As a result, your body may not have enough healthy blood cells, leading to problems like anemia (low red blood cells), infections (low white blood cells), and bleeding issues (low platelets). Sometimes, the body tries to make blood cells in other places, like the spleen or liver. This can cause these organs to become enlarged. Myelofibrosis is considered a type of myeloproliferative neoplasm, meaning it involves the overproduction of certain blood cells.

Symptoms

Myelofibrosis symptoms often develop slowly and can include feeling very tired (fatigue), shortness of breath, and a feeling of fullness under the left ribs due to an enlarged spleen. Other common signs are easy bruising or bleeding, night sweats, fever, and bone pain, which result from the bone marrow's inability to produce healthy blood cells.

Many people with myelofibrosis do not have symptoms in the early stages. When symptoms do appear, they are often related to the lack of healthy blood cells or an enlarged spleen. Anemia, a shortage of red blood cells, is a common problem. It can cause fatigue, weakness, and shortness of breath because your body isn't getting enough oxygen. You might also notice pale skin. An enlarged spleen (splenomegaly) is another frequent symptom. This happens when the spleen tries to take over blood cell production. It can cause pain or a feeling of fullness under your left ribs, which might make you feel full quickly after eating. Other symptoms can include easy bruising or bleeding, frequent infections, bone pain, fever, night sweats, and unexplained weight loss. These symptoms occur because the abnormal blood cell production and scarring affect the body's normal functions.

Causes & risk factors

Myelofibrosis is caused by genetic mutations in blood stem cells, most commonly in the JAK2 gene, but also in CALR or MPL genes. These mutations lead to abnormal blood cell production and scarring in the bone marrow. While the exact reason for these mutations is usually unknown, certain factors like older age, exposure to industrial chemicals, or previous radiation therapy can increase your risk.

The underlying cause of myelofibrosis is a change, or mutation, in the DNA of a single blood stem cell in the bone marrow. These mutations are not usually inherited from parents but happen during a person's lifetime. The most common mutation is in the Janus kinase 2 (JAK2) gene. Other less common mutations include those in the CALR (calreticulin) gene or the MPL (myeloproliferative leukemia virus) gene. These genes play a role in controlling the growth and division of blood cells. When they mutate, they send abnormal signals, leading to the overproduction of immature blood cells and the scarring of the bone marrow. While the exact reason these mutations occur is often unknown, certain factors can increase the risk of developing myelofibrosis. These include being older, typically over age 50, and having a history of exposure to certain industrial chemicals like toluene or benzene. Previous radiation therapy for other cancers can also be a risk factor.

How it's diagnosed

Diagnosing myelofibrosis involves a combination of physical exams, blood tests, and a bone marrow biopsy. A doctor will check for an enlarged spleen and order blood tests to look for abnormal blood cell counts. A bone marrow biopsy, where a small sample of bone marrow is taken, is crucial to confirm the scarring and identify specific genetic mutations that confirm the diagnosis.

If your doctor suspects myelofibrosis based on your symptoms and a physical exam, they will likely order several tests. A physical exam will include checking for an enlarged spleen or liver. Blood tests, such as a complete blood count (CBC) and a peripheral blood smear, are essential. These tests can show if you have anemia, abnormal white blood cell counts, or unusual platelet levels. They might also reveal immature blood cells circulating in your blood, which is a sign of the disease. The most definitive test is a bone marrow biopsy and aspiration. During this procedure, a doctor removes a small sample of liquid bone marrow (aspiration) and solid bone marrow tissue (biopsy), usually from your hip bone. These samples are then examined under a microscope to look for scarring and abnormal cells. Genetic tests on the bone marrow sample will also be performed to check for the common mutations, such as JAK2, CALR, or MPL, which help confirm the diagnosis and guide treatment.

Treatment options

Treatment for myelofibrosis aims to manage symptoms and slow disease progression, as there is currently no cure for most people. Options range from watchful waiting for those with mild symptoms to medications that reduce spleen size and improve blood counts, such as JAK inhibitors. For some, a stem cell transplant offers the only potential cure, though it carries significant risks, while other treatments like spleen removal or radiation may address specific complications.

The best treatment approach depends on your specific symptoms, age, overall health, and the risk level of your disease. For people with mild symptoms and low-risk disease, a "watchful waiting" approach may be recommended, where your doctor monitors your condition regularly without immediate treatment. Medications are often used to manage symptoms and complications. Janus kinase (JAK) inhibitors, such as ruxolitinib, fedratinib, pacritinib, and momelotinib, are commonly prescribed. These drugs can help reduce spleen size, improve symptoms like fatigue and night sweats, and sometimes improve blood counts. Other medications, like hydroxyurea, may be used to reduce high blood cell counts, and certain drugs (e.g., thalidomide-related drugs) can help with anemia. For younger, healthier individuals, an allogeneic stem cell transplant (also called a bone marrow transplant) is the only treatment that can potentially cure myelofibrosis. This procedure involves replacing your diseased bone marrow with healthy stem cells from a donor. However, it is a high-risk procedure with serious potential side effects and is not suitable for everyone. In some cases, if the spleen becomes too large and causes severe problems, surgical removal (splenectomy) or radiation therapy to the spleen may be considered to relieve discomfort.

Recovery & outlook

Myelofibrosis is a chronic condition, meaning it is long-lasting and requires ongoing management, but treatments can significantly improve quality of life and manage symptoms. The outlook varies greatly among individuals, depending on factors like age, specific genetic mutations, and overall health. While it can lead to serious complications, including progression to acute myeloid leukemia (AML) in some cases, many people live for years with the condition.

Living with myelofibrosis means managing a chronic illness. While there isn't a cure for most people, treatments are effective at controlling symptoms, reducing spleen size, and improving blood counts, which can significantly enhance your quality of life. Regular monitoring by your healthcare team is crucial to adjust treatments as needed and manage any emerging complications. Potential complications can include severe anemia, infections due to low white blood cell counts, and bleeding problems from low platelets. The enlarged spleen can also cause discomfort or lead to other issues. In a small percentage of people, myelofibrosis can transform into a more aggressive form of blood cancer called acute myeloid leukemia (AML). The outlook for individuals with myelofibrosis is highly variable. Factors that influence prognosis include your age at diagnosis, the specific genetic mutations present, your blood counts, and the presence of certain symptoms. Your doctor will use these factors to assess your individual risk and discuss the most appropriate management plan and expected course of the disease.

When to see a doctor

You should see your doctor if you experience persistent symptoms that could indicate myelofibrosis, such as unexplained fatigue, shortness of breath, a feeling of fullness or pain under your left ribs, or easy bruising and bleeding. Seek immediate medical attention if you develop a high fever, signs of severe infection, or uncontrolled bleeding, as these could be serious complications requiring urgent care.

It's important to talk to your doctor if you notice any new or worsening symptoms that are persistent and concerning. These include ongoing fatigue that doesn't improve with rest, unexplained weight loss, night sweats, or fevers. Pay close attention to symptoms related to an enlarged spleen, such as a feeling of fullness, discomfort, or pain in the upper left part of your abdomen. Also, report any unusual bruising, frequent nosebleeds, or bleeding gums, as these could indicate low platelet counts. Seek immediate medical attention if you experience severe symptoms like a sudden high fever with chills, which could signal a serious infection. Also, if you have any signs of significant bleeding, such as passing black or bloody stools, vomiting blood, or experiencing severe headaches with vision changes, contact emergency services right away. These could be signs of serious complications requiring urgent medical care.

Frequently asked questions

Is myelofibrosis a type of cancer?

Yes, myelofibrosis is considered a rare type of chronic blood cancer. It is a myeloproliferative neoplasm, meaning it involves the overproduction of abnormal blood cells in the bone marrow, which then leads to scarring.

What is the life expectancy for someone with myelofibrosis?

The life expectancy for someone with myelofibrosis varies greatly and depends on many factors, including age, specific genetic mutations, and overall health. While it is a chronic condition, treatments can help manage symptoms and improve quality of life, allowing many people to live for years. Your doctor can provide a more personalized assessment.

Can myelofibrosis be cured?

For most people, myelofibrosis is a chronic condition that cannot be cured. However, an allogeneic stem cell transplant (bone marrow transplant) is the only treatment that offers a potential cure. This procedure is high-risk and is typically considered only for younger, healthier individuals who meet specific criteria.

What is the role of the JAK2 gene in myelofibrosis?

The JAK2 gene is involved in controlling the growth and division of blood cells. In myelofibrosis, a mutation in the JAK2 gene is the most common cause. This mutation leads to abnormal signaling, causing the bone marrow to produce too many abnormal blood cells and develop scarring.

Why does myelofibrosis cause an enlarged spleen?

Myelofibrosis causes an enlarged spleen (splenomegaly) because the scarred bone marrow cannot produce enough healthy blood cells. The spleen, which normally filters blood and stores blood cells, tries to take over the job of making blood cells. This extra work causes the spleen to grow larger than its normal size.

Are there any lifestyle changes that can help manage myelofibrosis?

While lifestyle changes cannot cure myelofibrosis, maintaining a healthy lifestyle can help manage symptoms and improve overall well-being. This includes eating a balanced diet, getting regular, moderate exercise as tolerated, avoiding infections, and getting enough rest. Always discuss any lifestyle changes with your doctor to ensure they are appropriate for your specific condition.

Sources

• MedlinePlus — Myelofibrosis
• Mayo Clinic — Myelofibrosis
• Cochrane Library — Myelofibrosis