Diagnosing Myeloproliferative Neoplasms (MPNs)

• Polycythemia vera (PV)
• Essential thrombocythemia (ET)
• Primary myelofibrosis (PMF)
• Chronic myeloid leukemia (CML)
• Chronic eosinophilic leukemia (CEL)
• Chronic neutrophilic leukemia (CNL)

How are Myeloproliferative Neoplasms Diagnosed?

• Clinical evaluation
• Complete blood count with differential
• Molecular testing
• Bone marrow biopsy

Clinical Evaluation

One of the first steps in diagnosis is undergoing a clinical evaluation.  During this, your healthcare team will collect past medical history and ask about any previous diseases, hospitalizations, or other events of significance. 

Because MPNs cause an increase in the number of blood cells in your body, you may be at a higher risk of forming blood clots or having health emergencies, such as blood clots, heart attack, or stroke. In fact, 20% of MPN diagnoses are made after a patient had a thrombotic event. Your provider will ask if you have ever had any of these events in the past and assess your risk for future occurrences. 

A clinical evaluation usually involves a spleen examination. Your spleen is an organ that works to filter debris out of blood and creates white blood cells. Because myeloproliferative neoplasms result in too many blood cells, the spleen can have too many cells to clean. As a result, it can become enlarged and inflamed.  

Complete Blood Count with Differential

One of the key lab tests your provider will order if they suspect a myeloproliferative neoplasm is a test called a complete blood count (CBC) with differential. 

A CBC is a common blood test that is often used in routine wellness exams and annual visits. A CBC is used to measure how many of each type of cell is circulating within your blood. In general, a CBC measures the following:

• Red blood cells (RBC): high RBC counts are often observed in patients with PV
• Hemoglobin: High hemoglobin levels are seen in PV whereas low hemoglobin levels are often observed in PMF
• Hematocrit: High hematocrit levels may be seen in PV
• Platelets: High platelet levels are seen in patients with ET and low platelets can be seen in PMF
• White blood cell counts: Higher than normal WBC counts can be observed in CML and PMF

Abnormal results from a routine CBC are often one of the first signs that you may have a myeloproliferative neoplasm. To better pinpoint what blood cells are being produced in excess, a CBC with differential is ordered. As the name implies, this test will measure the 'different' white blood cells that are circulating in your body. 

The differential test looks at the five following types of white blood cells:

• Neutrophils
• Lymphocytes
• Monocytes
• Eosinophils
• Basophils

Examining the different types of white blood cells helps determine a differential diagnosis. High neutrophil counts may suggest CNL, whereas high eosinophil levels may suggest a patient has CEL. 

Molecular Testing

To determine if you may have an MPN, your provider will perform biomarker testing to better characterize your subtype of neoplasm. One of the initial molecular tests that will be performed will look to see if your DNA has the BCR-ABL1 gene. The BCR-ABL1 gene is found on the 'Philadelphia' chromosome. As a result, people who test positive for the gene are sometimes also referred to as Philadelphia chromosome-positive (or Ph+). This gene is present in patients diagnosed with Chronic Myeloid Leukemia (CML).  

If you are considered Philadelphia chromosome-negative (Ph-) and a diagnosis of CML is ruled out, your healthcare team will look to see if you carry another mutation known as JAK2 V617F. JAK2 is one of the most common mutations seen in patients with non-CML-associated MPNs. This mutation is seen in over 90% of patients with PV, as well as 60% of patients with ET or PMF.

If a patient is negative for both the BCR-ABL1 gene and JAK 2 V617F, NCCN guidelines recommend testing for other mutations including the following: 

• CALR mutation: About 20-25% of patients with ET or PMF that are not positive for the JAK2 V617F mutation will carry a CALR mutation.
• MPL mutation: Although uncommon, up to 4% of patients with ET and up to 8% with MPF may carry this mutation. 
• JAK 2 Exon 12 mutation: 2-3% of patients with PV may carry this mutation.

Bone Marrow Biopsy

Another test your healthcare team may perform is called a bone marrow biopsy. During a bone marrow biopsy, your doctor will take a sample of bone marrow, generally from the hip. Your healthcare team is looking to see if there is any scarring in the bone marrow and if there are any other genetic abnormalities.  

Based on the type of MPN that is suspected, your provider may order other tests specific to a certain neoplasm subtype. 

What Happens After I am Diagnosed with an MPN?

After a diagnosis is made, your healthcare team will evaluate your risk of disease. Most diseases are broken into low risk vs. high risk, although some may stratify the risk scoring out further. Your risk level will help aid in determining what treatments options are most appropriate for your individualized disease. 

Dr. Adrienne Phillips, a Hematologist and Medical Oncologist at Weill-Cornell/New York Presbyterian Hospital explains "Myleoproliferative Neoplasms (MPNs) is kind of a overreaching title of these diseases and the thereapy really depends on what the condition specifically is".. Examples of treatments options include, but are not limited to, the following:

• Preventative Medications: Low dose aspirin may be used in certain MPNs, such as ET, to decrease the risk of events like heart attack or stroke. 
• Cytoreductive therapy: This therapy refers to medications that are used to decrease the number of blood cells within the bone marrow. Examples include hydroxyurea, interferon alfa (2a and 2b), and busulfan.
• JAK Inhibitors: These drugs work upon the JAK pathway that is impacted by the JAK-2 mutations commonly seen in a majority of patients. The most common JAK inhibitor used is ruxolitinib (Jakafi©).
• Stem Cell or Bone Marrow Transplant: Transplant of stem cells or bone marrow may be considered. It is usually reserved for younger patients or those with aggressive disease. 

Other treatments may include chemotherapy and other tyrosine kinase inhibitors (TKIs). Because treatment is dependent on several factors (ex: type of MPN, risk factors, symptoms, etc.), it is important to ask your healthcare team what treatment options are right for you. 

Moving Forward – Questions to Ask Your Doctor

• What type of myeloproliferative disorder do I have?
• What is the prognosis of my MPN?
• How do my molecular testing results affect my prognosis?
• What treatment options are available to treat my MPN?

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