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Myeloproliferative neoplasms

This page was reviewed under our medical and editorial policy by

Haris Ali, MD, Hematologist-Oncologist, City of Hope | Duarte

Karamjeet Singh Sandhu, MD, Hematologist-Oncologist, City of Hope | Duarte

This page was updated on June 19, 2023.

Once referred to as myeloproliferative disorder, myeloproliferative neoplasms (MPNs) are a group of diseases in which the bone marrow makes too many red blood cells, platelets or white blood cells. MPN is a rare type of blood cancer.

According to the Leukemia & Lymphoma Society, around 20,000 people in the United States are diagnosed with a myeloproliferative neoplasm each year, and about 295,000 people are living with the disease.

The main types of myeloproliferative neoplasms under the latest World Health Organication (WHO) classification are:

  • Chronic myelogenous leukemia (CML)
  • Polycythemia vera (PV)
  • Primary myelofibrosis (PMF)
  • Essential thrombocythemia (ET)
  • Chronic neutrophilic leukemia
  • Chronic eosinophilic leukemia
  • Juvenile myelomonocytic leukemia
  • Myeloproliferative neoplasms, unclassifiable (MPN-U)

The unique characteristic of these conditions is that they have a driver gene mutation, which is responsible for cytokine-independent growth and overproduction of blood cells. This also causes a variety of symptoms, as described below in detail. These diseases become more challenging as the number of cells build up in the bloodstream and/or bone marrow and in some cases may be a precursor to leukemia.

This overview will cover the basic facts about MPNs, including:

Types of myeloproliferative neoplasms

MPNs are classified into subtypes based on:

  • Blood cell and platelet counts
  • Percentage of myeloid blasts in the bone marrow
  • Risk the disease will turn into leukemia

There are several types of MPNs:

CML: This is a slowly progressing disease that occurs when the bone marrow makes too many white blood cells, and it may not have any symptoms initially. A genetic mutation called the Philadelphia chromosome is typically found in the blood cells of CML patients.

PV: This condition occurs when too many red blood cells are produced in the bone marrow. Symptoms may include headaches, itching after bathing, reddened skin and/or fullness below the ribs on the left side. Genetic changes in the JAK2 gene are present in the vast majority of patients. This can evolve to myelofibrosis or acute leukemia.

PMF: This condition is characterized by abnormal blood cells and fibers in bone marrow. Symptoms may include pain below the ribs on the left side due to spleen enlargement and extreme fatigue. PMF may be caused by a genetic change to the JAK2 gene, MPL gene or CALR gene. Sometimes, PV and ET may progress to myelofibrosis, which is also called secondary MF.

ET: This condition is characterized by too many platelets in the bone marrow. With this type of condition, symptoms aren’t always present. Complications related to blood clots or bleeding could be what initially prompts patients to see the doctor. Essential thrombocythemia may be caused by a genetic change to the JAK2 gene, MPL gene or CALR gene. This can evolve to myelofibrosis or acute leukemia.

Chronic neutrophilic leukemia: In this condition, too many blood stem cells morph into a type of white blood cell known as neutrophils. When too many neutrophils form, the spleen and liver may swell. This disease may progress quickly to acute leukemia.

Chronic eosinophilic leukemia: In this disease, too many white blood cells, called eosinophils, are produced in the bone marrow. Symptoms may be related to deposits of eosinophils in the organs, and may include skin rashes, trouble breathing and impaired mobility.

MPN-U: These are MPNs that showcase some clinical, morphological or molecular features of myeloproliferative neoplasms, but they don’t fit in any of the subtypes listed above. MPN-Us make up approximately 5 percent to 10 percent of all myeloproliferative neoplasms.

Risk factors for myeloproliferative neoplasms

Risk factors for MPNs include:

  • Advancing age
  • Anemia
  • Genetic changes
  • Chromosome changes
  • Gender (males have a higher risk)
  • Tobacco use
  • Environmental exposures (high-dose radiation, long-term workplace exposure to benzene and certain chemicals used in the petroleum and rubber industries)

What are the MPN symptoms?

MPNs may not cause symptoms in the beginning. Oftentimes, people are diagnosed following a routine blood test. Symptoms may not be noticeable for months or years after a diagnosis.

However, if symptoms do develop, they may include:

  • Frequent headaches
  • Fatigue
  • Bruising
  • Unusual bleeding
  • Blood clots
  • Blurry vision
  • Ringing in the ears
  • Infections
  • Fullness below the ribs, typically on the left side
  • Fever (>100ºF)
  • Itching
  • Anemia
  • Unintentional weight loss in the last six months
  • Night sweats
  • High blood pressure
  • Filling up quickly after eating
  • Abdominal pain

MPN diagnosis and detection

In general, diagnosing MPNs involves blood testing and biopsy, including:

  • Routine blood test (also called a complete blood count, or CBC), used to detect abnormal types or numbers of red blood cells, white blood cells or platelets
  • Bone marrow biopsy, a minor procedure that allows the care team to get a sample of liquid marrow, called aspirate, and soft bone, called core
  • Cytogenetic analysis, which looks for chromosomes in blood or bone marrow cells (results can help predict the course and severity of the MPN)
  • Genetic testing, which looks for genetic mutations associated with MPNs
  • Physical exam
  • Radiological imaging, especially of the abdomen, to assess for an enlarged liver and spleen from the deposit of abnormal cells

MPN treatment

Treatment for MPNs is based on the specific type of disease, whether or not it is causing symptoms, and a person’s overall health status. Possible treatments for MPNs include:

Watchful waiting: Not all cases of MPNs will need treatment. Sometimes doctors will monitor for signs of symptoms of progression.

Targeted therapy: These drugs "target" specific cancer cells without affecting normal cells. Tyrosine kinase inhibitor (TKI) therapy, for example, blocks driver signals that cause cancer cell growth. ABL1 inhibitors in CML and JAK STAT inhibitors in PV and PMF may decrease elevated blood cell numbers, improve the size of the spleen and modulate the response of proteins playing a role in symptoms related to PV and certain types of myelofibrosis. In cases of CML, it may cause long-term remission.

Phlebotomy: A phlebotomy may be used to remove extra red blood cells and reduce the risk of a blood clot in polycythemia vera.

Transfusion therapy: Blood transfusions may be used to replace blood cells due to decreased production as a result of the disease or destruction as a result of cancer treatment.

Chemotherapy: These drugs are used to kill cancer cells or stop them from multiplying.

Radiation therapy: Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells.

Surgery: A surgeon may remove the spleen (via a splenectomy) if it’s enlarged.

Immunotherapy: Immunotherapy is used to shut down key proteins on immune cells that allow the cancer to go undetected by the body’s immune system. Interferon alfa and pegylated interferon alpha are commonly used immunotherapy drugs for some MPNs.

Stem cell or bone marrow transplant: This is currently the only potential curative treatment option in the majority of MPN diagnoses. It is, in essence, an immunotherapy. Stem cells are removed from the blood or bone marrow of healthy donors and infused to the patient (after treatment that destroys underlying MPN-causing cancer stem cells) so they can grow into healthy blood cells. For some types of MPNs, the procedure is preceded by high-dose chemotherapy.

Some treatments are used to reduce and manage symptoms.

For anemia, these medications may be recommended:

  • Erythropoietic growth factors
  • Steroids
  • Androgens
  • Immunomodulators

Anti-platelet agents may also reduce the risk of blood clots. Clinical trials with novel agents are encouraged, as they may help treat patients. 

Determining the prognosis of MPNs

A staging system hasn't been developed specifically for chronic myeloproliferative neoplasms as it has for solid tumors and lymphomas, because the MPN subtypes listed above each behave differently. Knowing the type of MPN helps physicians plan treatment. Each subcategory has a different prognostic scoring system to estimate prognosis and help determine treatment, so always talk to the care team about specific survival data and prognosis information.

Myeloproliferative neoplasm survival rate

Differences in survival are based on the type of disease:

  • Chronic myelogenous leukemia (CML): According to data from the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program, 70.4 percent of people with CML will still be alive five years after their diagnoses. These individuals are expected to have normal lifespans.
  • Essential thrombocythemia (ET): Life expectancy isn’t typically affected. Less than 10 percent of people with ET may develop acute leukemia, according to SEER data analyzed in Leukemia and Lymphoma.
  • Polycythemia vera (PV): Longevity isn’t always affected if the disease is monitored closely. On average, most people with PV live for around 20 years after their diagnosis, according to SEER data analyzed in Leukemia and Lymphoma.
  • Chronic neutrophilic leukemia (CNL): The median survival ranges from six months to 20 years from diagnosis, according to the SEER.
  • Chronic eosinophilic leukemia (CEL): SEER reports that the five-year survival is around 80 percent.
  • Primary myelofibrosis (MF): Unlike other MPNs, MF is more likely to be fatal. The five-year survival rate is 51 percent, according to SEER data analyzed in Leukemia and Lymphoma.

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