Myeloproliferative Neoplasms (MPN)

Myeloproliferative neoplasms (MPN), commonly called myeloproliferative disorders, are diseases of the bone marrow and blood. They can strike at any age, have no known cause and a wide range of symptoms and outlooks.

Sometimes the disease progresses slowly and requires little treatment; other times it develops into acute myeloid leukemia (AML).

To understand what happens to your blood when you have MPN, it helps to know what makes up normal blood and bone marrow. There are three major types of blood cells: red blood cells (RBCs), white blood cells (WBCs) and platelets. These cells are made in the bone marrow and flow through the bloodstream in a liquid called plasma.

Red blood cells (RBCs), the major part of your blood, carry oxygen and carbon dioxide throughout your body. The percentage of RBCs in the blood is called hematocrit. The part of the RBC that carries oxygen is a protein called hemoglobin. All body tissues need oxygen to work properly. When the bone marrow is working normally, the RBC count remains stable. Anemia occurs when there are too few RBCs in the body. Symptoms of anemia include shortness of breath, weakness and fatigue.

White blood cells (WBCs) include several different types. Each has its own role in protecting the body from germs. The three major types are neutrophils, monocytes, and lymphocytes.

• Neutrophils (also known as granulocytes or polys) destroy most bacteria.
• Monocytes destroy germs such as tuberculosis.
• Lymphocytes are responsible for destroying viruses and for overall management of the immune system. When lymphocytes see foreign material, they increase the body’s resistance to infection.

WBCs play a major role in fighting infection. Infections are more likely to occur when there are too few normal WBCs in the body.

Absolute Neutrophil Count (ANC) is a measure of the number of WBCs you have to fight infections. You can figure out your ANC by multiplying the total number of WBCs by the percentage of neutrophils (“neuts”). The K in the report means thousands. For example:

• WBC = 1000 = 1.0K
• Neuts = 50% (0.5)
• 1000 X 0.5 = 500 neutrophils

Also, when you receive your blood counts, this equation may be written as polys plus bands = neutrophils. Further, while anyone can catch a cold or other infections, this is more likely to occur when your ANC falls below 500. Your WBC count generally will fall within the first week you start chemotherapy, but it should be back to normal between 21 and 28 days after starting chemotherapy.

Platelets are the cells that help control bleeding. When you cut yourself, the platelets collect at the site of the injury and form a plug to stop the bleeding.

Bone marrow is the soft tissue within the bones where blood cells are made. All blood cells begin in the bone marrow as stem cells.

The bone marrow is made up of blood cells at different stages of maturity. As each cell fully matures, it is released from the bone marrow to circulate in the bloodstream. The blood circulating outside of the bone marrow in the heart, veins and arteries is called peripheral blood.

Stem cells are very immature cells. When there is a need, the stem cells are signaled to develop into mature RBCs, WBCs or platelets. This signaling is done with “growth factors.”

Myeloproliferative Neoplasms (MPN) Types

There are several types of myeloproliferative neoplasms. The main types are:

• Primary myelofibrosis affects the red blood cells and granulocytes, a type of white blood cell. The cells don't mature normally and are irregularly shaped. Primary myelofibrosis also causes thickening or scarring of the fibers inside bone marrow, which can decrease the production of red blood cells and cause anemia.
• Polycythemia vera (PV) is caused by the overproduction of red blood cells in the bone marrow, which then build up in the blood. Often, the spleen swells as extra blood cells collect there, causing pain or a full feeling on the left side. Itching all over the body is a symptom of PV.
• Essential Thrombocythemia (ET) means that the number of platelets in the blood is much higher than normal, while other blood cell types are normal. The extra platelets make the blood "sticky," which slows down blood flow.
• Chronic eosinophilic leukemia/hypereosinophilic syndrome (HES) is characterized by a higher than normal number of the white blood cells responsible for fighting allergic reactions and some parasitic infections (eosonophils). You may experience itching, swelling around the eyes and lips or swollen hands and/or feet. In some patients, HES may quickly progress to acute myelogenous leukemia.
• Systemic mastocytosis (SM) affects mast cells, which are found in skin, connective tissue and in the lining of the stomach and intestines. Mast cells serve as a sort of alarm system by signaling disease-fighting blood cells to target areas of the body where they're needed. They may also play a role in wound healing. SM is caused by too many mast cells accumulating in the body's tissues, which can eventually affect the spleen, bone marrow, liver or small intestine.

Myeloproliferative Neoplasms (MPN) Risk Factors

Anything that increases your chance of getting myeloproliferative neoplasms is a risk factor. These include exposure to:

• Intense radiation, such as a nuclear bomb
• Petrochemicals, such as benzene or toluene
• Electrical wiring

Many people with myeloproliferative neoplasms have a mutation in the JAK2 gene. This gene mutation is acquired, which means you are not born with it.

Some cases of myeloproliferative neoplasm can be passed down from one generation to the next. Genetic counseling may be right for you. Learn more about the risk to you and your family on our genetic testing page.

Myeloproliferative Neoplasms (MPN) Symptoms

Many times, especially in the early stages, myeloproliferative neoplasms (often called myeloproliferative disorders) do not have symptoms. When it does have signs, they vary from person to person. If you have symptoms, they may include:

• Headache
• Fatigue
• Shortness of breath
• Easy bruising or bleeding
• Petechiae (tiny red spots under the skin)
• Unexplained weight loss
• Night sweats
• Fever
• Pruritus (itching)

These symptoms do not always mean you have a myeloproliferative neoplasm. However, it is important to discuss any symptoms with your doctor, since they may signal other health problems.

Myeloproliferative Neoplasms (MPN) Treatment

Myeloproliferative neoplasms, often called myeloproliferative disorders, can be challenging to treat. Patients may require years of therapy and follow-up care. Treatments for MPN generally are aimed at controlling disease symptoms, and your symptoms will help the doctor decide which treatment is best. Therapies may include one or more of the following.

• Medications: Aspirin, hydroxyurea, anagrelide and interferon-alpha are the main medications for essential thrombocythemia and polycythemia vera. Ruxolitinib can be used in polycythemia vera patients not responding to hydroxyurea. For myelofibrosis, ruxolitinib and fedratinib (JAK inhibitors) are approved therapies. Thalidomide, steroids and other hormones, and cladribine also may be used.
• Blood or platelet transfusion
• Growth factors, which stimulate growth of bone marrow cells, are given as injections under the skin and may benefit myelofibrosis patients with low blood cell counts.
• Radiation therapy of the spleen in patients with myelofibrosis
• Surgical removal of the spleen in patients with myelofibrosis
• Phlebotomy for patients with polycythemia vera