Myelofibrosis

Myelofibrosis is a rare type of bone marrow cancer where scar tissue gradually replaces the healthy tissue that makes blood cells, leading to serious complications and changes in daily life that require careful management and support.

Table of contents

• What is myelofibrosis?
• Types of myelofibrosis
• Causes and risk factors
• Signs and symptoms
• How myelofibrosis is diagnosed
• Potential complications
• Treatment approaches
• Living with myelofibrosis
• Risk groups and outlook

What is myelofibrosis?

Myelofibrosis is a rare form of blood cancer that affects the bone marrow, which is the soft, spongy tissue inside bones where blood cells are made^[1]. In this condition, scarring develops in the bone marrow, making it difficult for the body to produce healthy blood cells^[2].

As the disease progresses, scar tissue called fibrosis builds up in the bone marrow, crowding out the normal cells^[3]. This scarring causes inflammation and prevents the bone marrow from functioning properly^[2]. When the bone marrow can no longer make enough blood cells, other organs like the spleen and liver may try to take over this job, which can cause them to become enlarged^[5].

Myelofibrosis belongs to a group of cancers called myeloproliferative neoplasms, which cause the body to make too many blood cells that don’t work properly^[1]. It is a lifelong condition that often progresses slowly, though sometimes it can worsen quickly^[2].

• Bone marrow
• Spleen
• Liver

Types of myelofibrosis

There are two main types of myelofibrosis^[2]:

Primary myelofibrosis occurs on its own without any previous blood disorder. This is the most common type^[2]. Researchers believe it may be caused by abnormal blood stem cells in the bone marrow that produce mature cells which grow quickly and take over the bone marrow^[3].

Secondary myelofibrosis, also called Post-ET/PV MF, develops when other blood conditions called essential thrombocythemia or polycythemia vera progress over time^[2]. These conditions are also myeloproliferative neoplasms where the bone marrow makes too many blood cells^[2].

Causes and risk factors

The exact cause of myelofibrosis is often unclear^[1]. The disease happens when the earliest form of a blood cell, called a stem cell, transforms into a cancer cell^[2]. This abnormal cell makes copies of itself that build up in the bone marrow, crowding out healthy cells and releasing substances that damage the bone marrow and lead to scarring^[2].

Many people with myelofibrosis have common changes in their genes called mutations^[2]. The most common mutations affect genes called JAK2, CALR, and MPL^[2]. About 50 to 60 percent of people with myelofibrosis have the JAK2 mutation^[3]. Between 5 and 10 percent have an MPL mutation^[3], and about 23.5 percent have a CALR mutation^[3].

Several factors may increase the risk of developing myelofibrosis^[2]:

• Being over age 60
• Having another blood disorder such as essential thrombocythemia or polycythemia vera
• Exposure to large doses of radiation (rare)
• Exposure to high levels of industrial chemicals like benzene (rare)

In the majority of cases, myelofibrosis is not inherited from parents and cannot be passed on to children, although some families do show a tendency toward the disease^[3].

Signs and symptoms

Many people with myelofibrosis have no symptoms for years, especially in the early stages of the disease^[3]. The disease often gets worse slowly, and symptoms may develop gradually^[2]. When symptoms do appear, the first ones are usually severe tiredness and an enlarged spleen^[2].

Common symptoms of myelofibrosis include^[1][2]:

• Feeling tired, weak, or short of breath
• Pain or fullness below the ribs on the left side (from an enlarged spleen)
• Feeling full after eating only a small amount of food
• Easy bruising or bleeding
• Night sweats that soak through clothing
• Fever
• Bone or joint pain
• Itching of the skin
• Weight loss without trying
• Problems concentrating
• Getting infections more easily

An enlarged spleen, called splenomegaly, may feel like heaviness in the upper left part of the belly, or the area may hurt^[2]. The liver may also become enlarged^[2].

Many of these symptoms are caused by low numbers of healthy blood cells or by inflammation in the body^[3]. It’s important to see a doctor if you have any symptoms that worry you^[1].

How myelofibrosis is diagnosed

Diagnosing myelofibrosis often begins with a physical exam, where your doctor will ask about your symptoms and check your body, including feeling your belly to see if your spleen or liver is larger than normal^[9]. Since some people with myelofibrosis don’t have symptoms, the disease is sometimes found during routine medical checkups^[3].

Several tests help confirm a diagnosis^[9]:

Blood tests are usually the first step. A complete blood count checks the number of red blood cells, white blood cells, and platelets in your blood^[14]. Most people with myelofibrosis have a low number of red blood cells, which is called anemia^[14]. White blood cell and platelet counts may be higher or lower than normal^[9].

Your doctor may also look at your blood under a microscope in a test called a blood smear^[2]. Additional blood tests can check for gene mutations like JAK2, CALR, or MPL^[14].

Bone marrow tests are required to confirm the diagnosis^[2]. These include bone marrow aspiration and biopsy, where a doctor uses a thin needle to remove a small sample of liquid bone marrow and a small piece of bone tissue, usually from the hip bone^[9]. Looking at this sample helps doctors see if scar tissue has replaced healthy bone marrow^[9].

Imaging tests such as ultrasound, CT scans, or MRI scans may be used to check the size of your spleen and liver and look for signs of scarring in the bone marrow^[9].

Potential complications

As myelofibrosis advances, several serious complications can develop^[2]:

Decreased blood cell production occurs as scar tissue crowds out normal cells in the bone marrow. This can lead to severe anemia or low platelet counts^[2].

Blood cell production outside the bone marrow happens when the spleen, liver, or other organs try to make blood cells that the bone marrow can no longer produce. This causes these organs to swell^[2].

High blood pressure in the portal vein, which carries blood from the spleen to the liver, can develop. Tumors from out-of-place blood cells can put too much pressure on this vein, potentially causing serious bleeding^[2].

Transformation to acute myeloid leukemia is the most aggressive complication. Myelofibrosis can progress to this severe form of leukemia^[2]. Bone marrow failure, blood clots, and transformation to leukemia are the main causes of illness and death in people with myelofibrosis^[3].

Treatment approaches

Treatment for myelofibrosis focuses on relieving symptoms and managing complications, as the disease is often not curable with medication alone^[1]. The best treatment depends on your symptoms, risk group, blood cell levels, and overall health^[14].

Some people don’t need treatment right away if they have no symptoms or only mild disease^[1]. Instead, they have regular checkups and blood tests to monitor the disease, an approach called watchful waiting^[13].

JAK inhibitor medications are important treatments for myelofibrosis. Several drugs in this class have been approved, including ruxolitinib, fedratinib, pacritinib, and momelotinib^[13]. These medications work by blocking proteins called Janus kinases that tell blood cells to grow and divide^[5]. They can help reduce spleen size and improve symptoms like itching, night sweats, and bone pain^[13].

Supportive care helps manage specific problems^[13]:

• Blood transfusions increase red blood cell counts to help with tiredness and weakness
• Growth factors stimulate blood cell production
• Androgens (male hormones) can boost blood counts
• Antibiotics prevent or treat infections
• Low-dose aspirin may reduce the risk of blood clots

Chemotherapy medications like hydroxyurea may be used to control high blood cell counts^[13].

Surgery to remove the spleen may be considered for people whose spleens remain very large despite other treatments^[13].

Radiation therapy can be helpful for specific problems like pain in bones or enlarged organs outside the spleen and liver^[13].

Stem cell transplant is the only treatment that can potentially cure myelofibrosis^[7]. In this procedure, called allogeneic hematopoietic stem cell transplantation, diseased bone marrow is replaced with healthy stem cells from a donor^[12]. This treatment is usually considered for people with high-risk disease or those with specific gene mutations that make the disease more dangerous^[13].

Living with myelofibrosis

Adjusting to life with myelofibrosis involves managing both physical symptoms and emotional challenges. Simple lifestyle changes can significantly improve your quality of life.

Managing fatigue is one of the biggest challenges. Plan important activities during times when you have the most energy, take rest breaks between tasks, and consider light exercise like walking or stretching to improve blood flow^[20]. Don’t hesitate to ask family or friends for help with household chores^[15].

Nutrition matters even though no diet can cure myelofibrosis. Eating iron-rich foods like spinach, lean red meat, legumes, and fortified cereals can help with anemia^[20]. Include high-fiber foods to prevent constipation from medications. Foods that fight inflammation, such as fatty fish, berries, nuts, and leafy greens, may support immune health^[20]. If you feel full quickly because of an enlarged spleen, try eating smaller meals throughout the day^[20].

Stay hydrated by drinking 6 to 8 glasses of water or other low-fat, low-sugar drinks each day, especially if you have night sweats^[19].

Keep active as much as you can. Regular physical activity can boost energy, improve mood, and help control weight^[19]. Work with your healthcare team to find the right exercises for you, aiming for about 150 minutes per week of moderate activity like walking or swimming^[16].

Manage other symptoms with practical steps. Use warm compresses or baths for bone and joint pain. Wear loose clothing if your spleen is enlarged. Practice good sleep habits by creating a peaceful bedtime routine^[20].

Stop smoking if you smoke, as it can worsen the effects of myelofibrosis and cause other health problems. The healthcare system offers support services to help you quit^[19].

Communicate with your healthcare team regularly. Keep a list of questions to bring to appointments, track your symptoms, and report any new problems right away^[21].

Find emotional support. Living with a chronic illness can bring feelings of frustration, sadness, and anxiety. Connect with family and friends, join support groups with others who have myelofibrosis, or talk with a counselor^[17]. Prayer, meditation, or deep breathing can help manage stress^[16].

Many people with myelofibrosis adjust their work schedules, reduce hours, or take early retirement^[15]. Be open with your employer about what accommodations might help, such as working from home or taking frequent breaks.

Risk groups and outlook

Doctors use scoring systems to determine how serious your myelofibrosis is and predict your outlook. The International Prognostic Scoring System (IPSS) at diagnosis and the Dynamic International Prognostic Scoring System (DIPSS) during treatment help classify patients into risk groups: low risk, intermediate-1, intermediate-2, and high risk^[14].

These risk groups depend on several factors^[14]:

• Your age (over 65 is higher risk)
• White blood cell levels (high counts mean higher risk)
• Hemoglobin levels (less than 100 grams per liter is higher risk)
• The number of immature blood cells called blasts in your blood
• Symptoms like weight loss or night sweats

Newer scoring systems also consider specific DNA changes in the myelofibrosis cells^[14].

Myelofibrosis affects each person differently. Low-risk disease can be kept under control for several years in some people, while high-risk disease can be more difficult to treat^[14]. The predicted outlook depends on many factors, and it’s best to discuss your specific situation with your specialist, who has access to all your test results and how they have changed over time^[14].

People are usually around 65 years old when they learn they have myelofibrosis^[5]. About 16,000 to 18,500 people in the United States have this condition^[5].