Primary myelofibrosis

Primary myelofibrosis is a rare blood cancer where excessive scar tissue builds up in the bone marrow, affecting the body’s ability to produce healthy blood cells and potentially leading to serious complications if left unmanaged.

Table of contents

• What is primary myelofibrosis?
• What causes this condition?
• Signs and symptoms
• How is it diagnosed?
• Treatment options
• Possible complications
• Living with myelofibrosis

What is primary myelofibrosis?

Primary myelofibrosis is a rare type of blood cancer that affects the bone marrow, which is the soft, spongy tissue inside your bones where blood cells are made^[1]. In this condition, excessive scar tissue forms in the bone marrow, impairing its ability to produce normal blood cells^[3].

This disease belongs to a group of cancers called myeloproliferative neoplasms, which means that the body makes too many abnormal blood cells that don’t work properly^[2][4]. When scar tissue builds up in the bone marrow, it becomes harder for the marrow to create healthy red blood cells, white blood cells, and platelets^[4].

As the condition progresses, blood cell production may move to the spleen or other areas of the body, causing the spleen to enlarge^[3]. Primary myelofibrosis is most often diagnosed in people over the age of 60, although there are known cases in younger individuals^[3].

There are two main types of myelofibrosis. Primary myelofibrosis occurs on its own and is the most common type. Secondary myelofibrosis develops when other blood conditions called essential thrombocythemia or polycythemia vera progress^[4].

aleukemic myelosis, bone marrow fibrosis, chronic idiopathic myelofibrosis, megakaryocytic myelosclerosis, myelosclerosis, osteomyelofibrosis

What causes this condition?

No one knows exactly what triggers the start of primary myelofibrosis^[3]. The disease happens when the earliest form of a blood cell, called a stem cell, transforms into a cancer cell that multiplies rapidly^[4]. These cancer cells crowd out healthy blood cells and release substances that damage the bone marrow, leading to scarring inside the bones^[4].

Researchers have discovered that most cases of myelofibrosis are caused by acquired gene mutations, which are changes in DNA that are not inherited from parents^[3]. In the majority of cases, myelofibrosis is not inherited genetically, meaning you cannot pass the disease on to your children or inherit it from your parents, although some families do show a clear predisposition^[3].

Several genetic mutations are commonly found in people with myelofibrosis. Approximately 50% to 60% of people with the condition have a mutation of the JAK2 gene within their blood-forming cells^[3][5]. Mutant JAK2 tells blood cells to grow and divide even when the body is not asking for more blood cells^[3].

About 23.5% of people with myelofibrosis have a mutation called Calreticulin, or CALR^[3]. Between 5 and 10% of patients have a mutation in the MPL gene, which affects the thrombopoietin receptor and the JAK signaling pathway^[3][5]. Some patients have none of these three mutations^[5].

Certain risk factors may increase the likelihood of developing myelofibrosis. Age is a significant factor, as the disease is most often diagnosed in people over 60^[3]. Environmental exposure to petrochemicals such as benzene and toluene, as well as ionizing radiation, may increase the risk of developing the condition^[3][4].

Signs and symptoms

Many people with myelofibrosis have no symptoms at first, and the condition may be discovered during routine medical examinations including complete blood counts^[3][5]. When symptoms do appear, they often develop slowly over time^[4].

The most common early symptoms are severe fatigue and an enlarged spleen^[4]. An enlarged spleen may feel like heaviness or fullness in the upper left area of the abdomen, or the area may hurt^[2][3]. Fatigue is caused by anemia, which means a low red blood cell count^[15].

Common symptoms of myelofibrosis include:

• Tiredness, weakness, or shortness of breath with mild exertion^[2][3]
• Bone pain and joint pain^[2][4]
• Feeling full after eating only a small amount of food^[2]
• Easy bruising or bleeding^[2][3]
• Sweating a lot while sleeping, so that you wake feeling covered in sweat^[2]
• Fever^[2][3]
• Weight loss or malnutrition^[3]
• Itching^[3][4]
• Susceptibility to infection^[3][4]
• Night sweats^[4]
• Problems concentrating^[4]

Other possible symptoms include an enlarged liver, abdominal distension or fluid retention if portal hypertension is present, compromised liver function, and abnormal growth of blood forming cells outside of the bone marrow^[3][5].

• Bone marrow
• Spleen
• Liver
• Blood

How is it diagnosed?

Myelofibrosis diagnosis often starts with a physical exam^[9]. Your healthcare professional may ask about your symptoms and examine your body. The health professional might feel your belly to check for signs of swelling in the spleen and liver^[9].

A healthcare professional might take a sample of blood for testing. One blood test used for myelofibrosis is a complete blood count, which counts the number of cells in a sample of blood^[9]. In people with myelofibrosis, this test often finds low numbers of red blood cells. White blood cell and platelet counts may be higher or lower than expected^[9].

Imaging tests make pictures of the inside of the body. For myelofibrosis, a healthcare professional might use the pictures to see whether the spleen and liver are larger than usual^[9]. They also may look for signs that scar tissue has replaced healthy tissue in the bone marrow. Imaging tests might include computerized tomography scans (CT scans) and magnetic resonance imaging scans (MRI scans)^[9].

Bone marrow aspiration and biopsy are procedures that involve collecting cells from the marrow^[9][5]. In a bone marrow aspiration, a healthcare professional uses a thin needle to remove a small amount of liquid bone marrow, usually taken from a spot in the back of the hip bone. A bone marrow biopsy is often done at the same time, removing a small piece of bone tissue and the enclosed marrow^[9].

Testing for gene mutations is an important part of diagnosis. If myelofibrosis is present on a bone marrow biopsy, testing for JAK2, CALR, and MPL mutations should be performed^[5]. Sometimes next generation sequencing with a myeloid-directed panel is used^[5].

Treatment options

Some people with myelofibrosis have no symptoms and might not need treatment right away^[2]. If you aren’t experiencing any symptoms, treatment may not be necessary, though your doctor will want to monitor your health closely and frequently for signs of disease progression through regular checkups and laboratory tests. This is referred to as “watchful waiting”^[15].

Treatment for myelofibrosis typically focuses on relieving symptoms^[2][10]. The main current treatment options can be divided into disease-modifying therapeutics and palliative measures, using an individualized patient-based approach^[10].

Several medications called JAK inhibitors are approved for the treatment of myelofibrosis. Four Janus kinase (JAK) inhibitors are approved by the US Food and Drug Administration for this purpose: ruxolitinib (Jakafi), fedratinib (Inrebic), pacritinib (Vonjo), and momelotinib (Ojjaara)^[13]. These medications work by blocking proteins involved in abnormal blood cell production and can help reduce symptoms and spleen size^[13].

Other treatment options may include blood transfusions to increase red blood cell count and help with weakness and fatigue^[15]. Additional chemotherapeutic agents, such as hydroxyurea, may be used to manage certain symptoms^[13]. Patients with refractory splenomegaly may be candidates for splenectomy, which is surgical removal of the spleen^[13].

Radiation therapy is most useful for patients with certain complications, such as post-splenectomy hepatomegaly, non-hepatosplenic extramedullary hematopoiesis, primary myelofibrosis-associated pulmonary hypertension, or extremity bone pain^[13].

Stem cell transplantation (also called hematopoietic stem cell transplantation or HSCT) remains the only curative option available for primary myelofibrosis^[10]. Patients with high or intermediate-2 risk disease, or those with high-risk mutations, should be considered for this treatment^[13].

Possible complications

As myelofibrosis advances, it can lead to several serious complications^[4]. The scar tissue can crowd out the normal cells in the bone marrow, leading to decreased blood cell production. This can result in anemia or low platelets^[4].

Blood cells unable to form in the bone marrow may develop in the spleen, liver or other organs, a process called extramedullary hematopoiesis^[4][5]. This can cause these organs to enlarge and may disturb their function^[5].

High blood pressure can develop in the portal vein, which carries blood from the spleen to the liver. Tumors from the out-of-place blood cells can put too much pressure on this vein, which can cause serious bleeding^[4].

One of the most serious complications is that myelofibrosis can progress to acute myeloid leukemia (AML), the most aggressive form of leukemia^[4][5]. Rapidly progressive, chemotherapy-incurable acute leukemia develops in approximately 30% of patients^[5].

Living with myelofibrosis

Myelofibrosis is a lifelong condition that often progresses slowly, though sometimes it gets worse fast^[4]. Whether or not you have symptoms, learning to live with myelofibrosis and making certain lifestyle adjustments can significantly improve your quality of life.

A balanced diet provides the nutrients the body needs, gives energy, and helps with weight control^[16]. Your menu should include lots of different fruits and vegetables, whole grains, proteins like chicken, turkey, eggs, beans, low-fat dairy and soy, and healthy fats like olive oil, avocados and nuts^[16]. You should dial way down on red meat, salt, processed meats, saturated fats and trans fats, and sugary drinks and sweets with added sugar^[16].

Being active is good for you in many ways. Exercise can give you more energy, brighten your mood, help control your weight, keep you more mobile over the years, and help keep diseases away^[16]. You can get benefits from activities like walking, swimming, dancing, jogging, stretching, tai chi, yoga, and riding your bicycle^[16]. If you haven’t done much exercise up to now, ease into it, and your medical team can help you decide how to start^[16].

Regular rest can help with the fatigue that can happen with myelofibrosis^[16]. Creating a sleep routine will help. This includes going to sleep and waking up at the same time every day, ensuring the bedroom is quiet, dark and relatively cool, and avoiding caffeine and alcohol close to bedtime^[18].

Fatigue may affect your ability to work. Many people with myelofibrosis decide to reduce their work hours or take an early retirement^[15]. You can ask your boss to work from home, if possible, or take frequent breaks during the workday^[15]. It’s important to ask for help from family or friends with household chores or hire a cleaning person^[15].

Emotional ups and downs are normal, but if you get the blues and can’t shake them off in a couple of weeks, check with your medical team, as counseling might help^[16]. As a member of a support group, you can learn how other people deal with the same issues that affect you^[16]. It’s also important to make time for things you enjoy, which can be anything from reading to taking a walk to relaxing in a warm bath^[16].

You’ll likely need to maintain a schedule of regular checkups and laboratory tests. It may be a good idea to keep a calendar, planner, or mobile app to keep track of your appointments^[15].