Myelofibrosis , also known as agogenic myeloid metaplasia, is a rare condition that causes progressive scarring (fibrosis) of the bone marrow, leading to abnormal blood cell counts and other serious complications. Some people with this condition may have no symptoms or need immediate treatment. Others suffer aggressive disease and develop severe anemia, liver dysfunction, and an enlarged spleen. Myelofibrosis can be diagnosed with blood tests and bone marrow biopsies. The only known cure is stem cell transplantation .
Types of myelofibrosis
Myelofibrosis is classified as a myeloproliferative neoplasm , a group of diseases characterized by the overproduction of at least one type of blood cell. A neoplasm refers to an abnormal overgrowth of tissue that is characteristic of both malignant and benign tumors.
Myelofibrosis is a complex disease that can be classified as a primary or secondary neoplasm.
- Primary myelofibrosis is a form of the disease that develops spontaneously in the bone marrow. It is often called primary idiopathic myelofibrosis (idiopathic means "of unknown origin").
- Secondary myelofibrosis is a type in which changes in the bone marrow are caused by another disease or condition. Therefore, myelofibrosis is considered secondary to the primary cause.
Myelofibrosis causes progressive failure of the bone marrow, impairing its ability to produce red blood cells (responsible for transporting oxygen and removing waste from the body), white blood cells (responsible for immune defenses), and platelets (responsible for blood clotting). blood).
When this happens, the hematopoietic cells of other organs in the body are forced to take over, putting undue pressure on the organs and causing them to swell.
Common symptoms of myelofibrosis include :
- Fatigue and weakness
- Difficulty breathing
- Unhealthy pale look
- Bloating and abdominal pain
- Easy bruising and bleeding
- Loss of appetite and weight.
- Increased risk of infection, including pneumonia.
- Skin nodules (cutaneous myelofibrosis )
As the disease progresses and begins to affect multiple organs, it can lead to serious complications, including:
Myelofibrosis is associated with genetic mutations in the hematopoietic (hematopoietic) cells of the bone marrow. It is not entirely clear why these mutations occur, but when they do occur, they can be transmitted to new blood cells. Over time, the proliferation of mutated cells can overwhelm the bone marrow's ability to produce healthy blood cells.
Mutations most closely associated with myelofibrosis include the JAK2, CALR, or MPL gene. About 90% of cases are associated with at least one of these mutations, while 10% have none of these mutations .
The JAK2 V617F mutation is the most common gene mutation and alone can trigger the development of myelofibrosis .
Known risk factors associated with primary and secondary myelofibrosis include :
- Family history of myeloproliferative disease.
- Jewish origin
- Advanced age
- Certain autoimmune diseases, especially Crohn's disease.
Secondary myelofibrosis is also associated with other diseases or conditions that directly or indirectly affect the bone marrow, including :
If your healthcare provider suspects you may have myelofibrosis, the diagnosis usually begins with your medical history (including risk factors) and a physical exam to check for an enlarged liver or spleen or abnormal nodules on the skin.
The next steps in diagnosing myelofibrosis are likely to be blood tests and imaging tests. Your blood test panel will likely include:
Imaging tests, such as x-rays, computed tomography (CT) , or magnetic resonance imaging (MRI) , can help detect organ enlargement, vascular strain, or abnormal bone hardening ( osteosclerosis ) common with myelofibrosis .
A bone marrow biopsy is usually used to look for characteristic changes in the bone marrow and determine the stage of the disease. It consists of inserting a long needle in the center of the bone to extract a bone marrow sample. A bone marrow biopsy is a moderately invasive procedure that can be performed on an outpatient basis under local anesthesia .
To make a correct diagnosis, your doctor will rule out other possible causes of your symptoms (this is called a differential diagnosis ). Chief among these are other classic chronic myeloproliferative neoplasms, including:
- Chronic myeloid leukemia
- Polycythemia vera
- Essential thrombocythemia
- Chronic neutrophilic leukemia
- Chronic eosinophilic leukemia
The diagnosis of these diseases does not necessarily mean the absence of myelofibrosis. In some cases, myelofibrosis may be secondary to the underlying disease, especially in polycythemia vera and essential thrombocythemia.
This is primarily intended to relieve symptoms, improve blood cell counts, and prevent complications. One potential cure for myelophirosis is bone marrow / stem cell transplantation .
Ultimately, treatment decisions are made based on:
- You have symptoms
- Your age and general health
- Risks associated with your particular case
If you are asymptomatic and at low risk for complications, you may only need regular monitoring to see if the disease progresses. No other treatment is required.
If you have symptoms, your main focus should be treating severe anemia and splenomegaly. If you have severe symptoms, a bone marrow transplant may be recommended.
Anemia is a condition in which you do not have enough healthy red blood cells to supply enough oxygen to the body's tissues. This is one of the most common features of myelofibrosis and can be treated or prevented with the following interventions :
- Blood transfusion is used to treat severe anemia and is often given intermittently in people with severe myelofibrosis. Medications for anemia such as Epogen (epoetin alfa) may be prescribed if the kidney is affected. An iron-rich diet, along with iron, folate, and vitamin B12 supplements, can also help.
- Androgen therapy involves injections of synthetic male hormones such as danocrine (danazol) to stimulate the production of red blood cells. Androgen therapy can cause masculinizing effects in women and increase the risk of liver damage with long-term use.
- Glucocorticoids are types of steroid medications that reduce systemic inflammation and can improve red blood cell counts. Prednisone is the most commonly prescribed steroid, but it should be noted that long-term use can cause cataracts and increase the risk of infection.
- Immunomodulatory medications such as thalomide (thalidomide), revlimid (lenalidomide), and pomalist (pomalidomide) can help increase the number of red blood cells while decreasing the enlargement of the spleen.
Women of reproductive age should never take this drug as it is known to cause serious birth defects.
Treatment of splenomegaly
In myelofibrosis, the spleen is the organ most susceptible to bone marrow failure, as it has a high concentration of hematopoietic cells. There are several treatment options for splenomegaly associated with myelofibrosis :
- Chemotherapy drugs such as hydroxyurea and cladribine are often used as the first line of treatment for splenomegaly to reduce swelling and pain.
- Jakafi (ruxolitinib) is a chemotherapy drug that targets the JAKS mutations most commonly associated with myelofibrosis. Jakafi can cause nausea, diarrhea, liver inflammation, low platelets, and high cholesterol in some cases.
- Splenectomy , the surgical removal of the spleen, may be recommended if the spleen becomes so large that it causes pain and increases the risk of complications. Although there are risks associated with any surgery, splenectomy generally does not affect life expectancy or quality of life.
- Radiation therapy may be considered if splenectomy is not an option. Side effects can include nausea, diarrhea, fatigue, loss of appetite, skin rashes, and hair loss (usually temporary).
Stem cell transplantation
Bone marrow transplantation, also known as a stem cell transplant , is a procedure used to replace diseased bone marrow with stem cells from healthy bones. For myelofibrosis, the procedure is called an allogeneic stem cell transplant (which means that a donor is required) .
A bone marrow transplant can cure myelofibrosis, but it is also associated with a high risk of life-threatening side effects. This includes graft-versus-host disease , in which cells from the graft attack healthy tissue .
Before your transplant, you will undergo a course of treatment (including chemotherapy or radiation therapy) to destroy any diseased bone marrow. You will then receive an intravenous (IV) infusion of stem cells from a compatible donor. Conditioning helps reduce the risk of rejection by suppressing the immune system, but it also puts you at high risk for infection.
Because of these risks, a thorough examination is necessary to determine if you are eligible for a stem cell transplant.
Based on current data, the median survival time for people with myelofibrosis is 3.5 to 5.5 years from diagnosis. However, this does not mean that you only have three to five years to live. if myelofibrosis is diagnosed.
Many factors affect the estimated life expectancy of people with myelofibrosis. For example, receiving a diagnosis before age 55 increases your average survival rate to 11. Some people live even longer.
Other factors that can increase survival time include:
- Be under 65 years of age at the time of diagnosis.
- Hemoglobin exceeds 10 grams per deciliter (g / dL)
- White blood cell count less than 30,000 per microliter (ml)
The severity of symptoms (including an enlarged spleen, fever, night sweats, and weight loss) also influences life expectancy.
Living with any life-threatening medical condition can be stressful. If you or your loved one is diagnosed with myelofibrosis, the best way to manage and support the recommended treatment is to stay healthy.
The MPN Coalition, a non-profit organization that supports people with myeloproliferative neoplasms, recommends eating a healthy Mediterranean diet . This includes replacing butter with healthy oils and limiting red meat to once or twice a month.
Because myelofibrosis can weaken the immune system, it is important to avoid getting:
- Wash your hands regularly.
- Avoid people with colds, flu, or other infectious diseases.
- Wash fruits and vegetables
- Avoid raw meat, fish, eggs, or unpasteurized milk.
It is also important to have the support of family, friends, and your health care team, and to seek the help of a therapist or psychiatrist if you experience major depression or anxiety. Regular exercise can also help improve mood and sleep, in addition to its physical benefits.
It also helps connect with support groups to connect with other people living with myelofibrosis who can offer professional support, advice, and guidance. Online support groups can be found on Facebook and through the MPN Research Foundation, a nonprofit organization.
Get the word of drug information
So far, the survival time of people with primary myelofibrosis appears to be more closely related to their symptoms and blood abnormalities than to any treatment or treatment modality.
Therefore, the disease must be treated on an individual basis, weighing the potential benefits and risks at each stage of the disease. If you are unsure of the recommended treatment or think you are not being aggressive enough, do not hesitate to seek the advice of a qualified hematologist or oncologist specializing in myeloproliferative neoplasms.