Myelofibrosis Diagnosis & Treatment

The process of a myelofibrosis diagnosis and treatment involves input from an experienced care team and the patient. A diagnosis is typically achieved through various blood, bone marrow, and molecular testing. Treatment plans for patients with MF will vary based on the severity of the disease, risk factors, and the symptoms the patient is experiencing. 

What is myelofibrosis?

Myelofibrosis is a condition that affects the bone marrow, which is the spongy tissue inside your bones responsible for producing blood cells. In human terms, it’s like the control center for making blood cells in your body. Myelofibrosis disrupts this process.

To offer more insight, Dr. Tania Jain, an assistant professor of oncology a Johns Hopkins Medicine and director of the Adult CAR-T Cell Therapy Program at the Sidney Kimmel Comprehensive Cancer Center explains exactly what myelofibrosis is. D

“The premise of myelofibrosis starts with the overactivation of the JAK/STAT pathway, which is supposed to be a normal functional pathway that’s supposed to do regular stuff and make blood cells,” says Dr. Jain.

She adds, “When it’s over-activated or activated without any restrictions, that’s when undesirable things happen, which can include affecting the bone marrow function in a negative way.

You could be making too many cells or you could alter the bone marrow function in the way that there is more scarring in the bone marrow, which is the fibrosis in the term myelofibrosis, which again affects the ability of the bone marrow to function normally whose job is to make a normal quantity and quality of blood cells.

As a result, patients can get anemic or have low hemoglobin, which can cause tiredness, fatigue, difficulty breathing, and related symptoms.

By virtue of the JAK/STAT pathway activation, this systemic or generalized inflammation that we often notice or patients leads them to a workup. What that results in is what we in our clinic call constitutional symptoms or symptoms that could be nonspecific or vague as sometimes labeled.

Those can include things like night sweats, low appetite, or other symptoms resulting from an enlarged spleen like abdominal discomfort, which are other symptoms that can sometimes lead to further investigations clinically.”

How is myelofibrosis diagnosed?

Myelofibrosis can be a complex disease to diagnose because physical symptoms don’t often present themselves until the later stages. However, several diagnostic tests are in place to help detect and track myelofibrosis at all stages of the disease.

Physical exam

It’s essential to get a yearly physical exam even if you feel 100% healthy. Regular check-ups are how cancers like myelofibrosis are detected at an early stage. During your exam, you should mention if you are experiencing any myelofibrosis symptoms to the doctor. 

If you have myelofibrosis, some signs that may come up during a routine physical exam include:

• Elevated or low blood pressure or pulse
• Swollen lymph nodes
• Enlarged spleen
• Unusual lumps in your abdomen

While the above signs may mean that a patient has myelofibrosis, they could also indicate any number of diseases. Therefore, the doctor will need to perform further tests in order to provide any type of diagnosis. 

Blood tests

Blood tests are typically part of any regular physical exam. However, your doctor may order additional blood work if there is a suspicion of myelofibrosis. Blood tests used to diagnose myelofibrosis include:

• Complete Blood Count (CBC) with Differential – Measures the number of blood cells in addition to hemoglobin and hematocrit (% of blood made up of red blood cells). Individuals with MF typically have a low level of red blood cells and abnormal levels of white blood cells and platelet counts. 
• Peripheral Blood Smear – Where pathologists examine the size, shape and appearance of blood cells under a microscope. Additionally, the test checks for the presence of immature blood cells in the blood. Individuals with MF often have malformed red blood cells in the shape of a teardrop and immature blood cells in the blood.
• Blood Chemistry Profile – Measures the levels of certain substances in the blood released by organs and tissues to measure how well a person’s kidneys are functioning. High levels of uric acid, lactic dehydrogenase (LDH), alkaline phosphatase and bilirubin may indicate a potential diagnosis of myelofibrosis. Additionally, measurements of levels of erythropoietin, ferritin and iron can inform doctors about the possible progression of the disease.

A complete blood count is typical when getting routine blood work done, while a peripheral blood smear and blood chemistry test may indicate that your doctor is looking into a potential diagnosis. 

Bone marrow tests

A doctor typically orders a bone marrow test to confirm a myelofibrosis diagnosis. Bone marrow tests are performed in two parts, typically performed at the same time:

• Bone marrow aspiration – A thin needle removes a small amount of liquid bone marrow.
• Bone marrow biopsy – A small amount of bone marrow is removed from the inside of a bone. 

Testing the bone marrow is typically how a doctor can differentiate myelofibrosis from other myeloproliferative neoplasms (MPNs). If a patient has MF, the samples will show elevated numbers of megakaryocytes of unusual size and shape. Additionally, in more advanced cases of MF, the bone marrow will show signs of scarring. 

Molecular testing

Since myelofibrosis is commonly linked to the mutation of a gene, another tool that doctors use to diagnose and form a treatment plan for MF is molecular testing. These tests look at potential abnormal changes in the body’s genes, proteins or chromosomes. Types of molecular testing used for a myelofibrosis diagnosis include:

• Polymerase Chain Reaction (PCR) – Detects gene mutations that are too small to be seen with a microscope. 
• Cytogenetic Analysis (Karyotyping) – Examines the chromosomes for any abnormal changes. For example, patients with MF sometimes have missing, broken or rearranged chromosomes. 
• DNA Sequencing – There are several different types of laboratory tests that look at the order (sequence) of DNA. About 90% of patients with MF have a mutation of one of three following genes:
  • JAK2 – 60%
  • CALR – 25% to 30%
  • MPL – 5% to 8%

Source: leukemia & lymphoma society

About 10% of myelofibrosis patients do not have one of the above mutations. Further research is being done to identify other mutations contributing to the onset of myelofibrosis. 

What are the criteria for diagnosing myelofibrosis?

In 2016, the World Health Organization (WHO) set diagnostic criteria for primary myelofibrosis. To be diagnosed with MF, a patient must meet all three of the major criteria below and at least one of the minor criteria in two consecutive tests.

Major Criteria

1. Proliferation of abnormal megakaryocytes accompanied by fibrosis in the bone marrow.
2. Exclusion of other diseases defined by World Health Organization criteria, such as essential thrombocythemia, polycythemia vera, BCR-ABL1+ chronic myeloid leukemia, myelodysplastic syndromes or other myeloid neoplasms.
3. Presence of JAK2, CALR, or MPL mutation or another clonal marker (gene mutation) such as genes ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1 or the absence of reactive myelofibrosis.

Minor Criteria

1. Another condition does not cause anemia
2. White blood cell count greater than or equal to 11 × 109/L
3. Palpable enlarged spleen
4. Lactate dehydrogenase (LDH) level above normal upper limits, or
5. Presence of immature blood cells in the peripheral blood (called “leukoerythroblastosis”)

It’s helpful to know the diagnostic criteria for MF if you are being assessed for the disease, as it allows you to understand the results of your tests and advocate for the proper testing for a potential diagnosis.

Myelofibrosis risk groups

Patients diagnosed with myelofibrosis are typically placed into a risk group based on the threat the disease poses to their health using the International Prognostic Scoring System (IPSS). However, if the disease progresses or becomes more hazardous during treatment, a doctor can reclassify a patient’s risk group per the Dynamic International Prognostic Scoring System (DIPSS).

The four risk groups into which a patient can fall include:

• Low-risk – no risk factors
• Intermediate 1 – one risk factor
• Intermediate 2 – two or three risk factors
• High-risk – four or more risk factors

The risk factors that determine your risk group include:

• Being 65 or older
• Symptoms that impact the entire body (constitutional symptoms)
• Hemoglobin lower than 10 g/dL
• Platelet count less than 100 x109 /L
• White blood cell count greater than 25 x109 /L
• Peripheral blood blasts greater than 1 percent
• If there is a need for a transfusion
• Presence of a complex karyotype (three or more unrelated abnormalities in a chromosome)

Patients who are in the low-risk group and are not experiencing any symptoms may not need any treatment at all. In these instances, it’s essential to routinely check on the progress of the disease to determine if any action is required.

Myelofibrosis treatments

Treatment for myelofibrosis varies based on the risk group a patient falls in and the symptoms the individual is experiencing. For example, those with few symptoms may only require a low dose of aspirin and bi-annual check-ins. In contrast, those with several risk factors may require more aggressive treatment and frequent check-ins. 

MORE>>> Discover the latest in Myelofibrosis Treatments

Treatments for anemia

A common complication of MF is anemia. This is because the scarring of the bone marrow prevents your body from making enough blood cells. Some common treatments for patients with MF that have anemia include:

• Blood Transfusions – occasional transfusions can help increase the supply of red blood cells in your body and improve symptoms commonly associated with anemia like fatigue. 
• Medications – thalidomide and lenalidomide are two prescription medications that can help improve red blood cell count and therefore treat the symptoms of anemia in patients with MF. Occasionally these medications will be combined with steroids to maximize the impact. 
• Androgen therapy – androgen, a male hormone, can improve your bone marrow’s ability to produce red blood cells. A synthetic version of the hormone is sometimes given to patients with anemia. 

Treatments for an enlarged spleen

An enlarged spleen is another common complication of myelofibrosis. The enlargement of the spleen is taken very seriously as it can impact other organs in the body. Some common treatments for those with MF who have an enlarged spleen include:

• Targeted drug therapy – medications including Jakafi and Interferon target abnormalities within the cancer cells specific to those with myelofibrosis. 
• Chemotherapy –  Hydroxyurea is an oral chemotherapy drug used to kill cancer cells.
• Splenectomy – If medical prescriptions and other treatment options don’t reduce the size of your spleen, then your doctor may suggest that the spleen be surgically removed to help prevent further complications. 
• Radiation therapy – target exposed to x-rays and protons can be applied to the spleen. This is typically used as an option when completing a splenectomy is too risky.

Bone marrow (stem cell) transplant

Occasionally a doctor will recommend a bone marrow transplant for patients who are younger and in relatively good health. This involves implanting the stem cells of a compatible donor into the person with myelofibrosis in hopes that the body will produce healthy blood cells. 

Bone marrow transplants are only done following an intensive course of chemotherapy. There are several complications associated with bone marrow transplants, but ultimately it could be a potential cure for MF. 

Clinical trials for myelofibrosis

If the potential treatment options aren’t feasible or are too high risk, your doctor may recommend you consider joining a clinical trial. This affords patients the opportunity to have access to an experimental treatment that otherwise would not be available to them. Check out the Mayo Clinic’s website for a complete list of myelofibrosis clinical trials.

Mental Health and Coping with Myelofibrosis

Taking care of your mental health and finding the right support resources are essential when dealing with a cancer diagnosis and going through the treatment process. Learning more about the disease and finding a really strong support system are just two of the ways you can start to process your diagnosis.

To learn more about the mental aspects of myelofibrosis, visit our mental health and cancer support pages.