Types of MPN
What are the different types of MPN?
There are four main types of MPNs that together represent around 95 per cent of all cases:
- chronic myeloid leukaemia
- polycythaemia (rubra) vera (PV)
- essential thrombocythaemia (ET)
Less common types of myeloproliferative neoplasms include:
- chronic neutrophilic leukaemia (CNL)
- chronic eosinophilic leukaemia (CEL)/hypereosinophilic syndrome
- chronic myelomonocytic leukaemia (CMML)
- systemic mastocytosis
- myeloproliferative disease.
Polycythaemia (rubra) vera, also known as primary polycythaemia vera, is a disorder in which too many red cells are produced in the bone marrow without any identifiable cause. These cells accumulate in the bone marrow and in the blood stream where they increase the blood volume and cause the blood to become thicker than normal. In many people with PV too many platelets and white cells are also produced. In secondary or reactive PV, red cell production is increased in response to excess amounts of erythropoietin (a red cell growth factor) circulating in the bloodstream.
The natural course of PV can vary considerably between individuals. In many patients, with treatment the disease remains stable for long periods of time, often many years. In around one third of all cases, PV transforms over time into another type of MPN called myelofibrosis, and in up to 10% of cases PV transforms into acute myeloid leukaemia.
In some people, PV progresses over time despite treatment. The spleen may become increasingly enlarged and in selected cases, surgical removal of the spleen or low dose radiation to the spleen may be required to relieve symptoms. Anaemia and thrombocytopenia (low numbers of circulating platelets) is common as the bone marrow is no longer able to produce adequate numbers of red cells or platelets. In addition, abnormal immature blood cells known as blast cells may start to appear in the blood.
Treatment during this time may involve blood transfusions if required, pain relief and careful myelosuppression. Your doctor is the best person to give you an accurate prognosis regarding your disease as he or she has all the necessary information to make this assessment.
Essential thrombocythaemia (ET) is a disorder in which too many platelets are produced in the bone marrow. Platelets are normally needed in the body to control bleeding. However, excess numbers of platelets can lead to abnormal blood clotting which can block the flow of blood in the blood vessels.In ET the blood platelet count is persistently elevated as a result of increased bone marrow production of platelets, in the absence of any identifiable cause.
ET is regarded as an incurable disease but in many people, with treatment the disease remains stable for long periods of time, often 10-20 years or more. In the longer term, a small number of people with ET may develop myelofibrosis. The risk of ET transforming to acute myeloid leukaemia is relatively low (1-2%).
Under normal conditions, the bone marrow provides a fine network of reticulin fibres on which the stem cells can divide and grow. Specialised cells in the bone marrow known as fibroblasts make these fibres. In myelofibrosis, chemicals released by high numbers of platelets and abnormal megakaryocytes (platelet forming cells) over-stimulate the fibroblasts. This results in the overgrowth of thick coarse fibres in the bone marrow, which gradually replace normal bone marrow tissue. Over time this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. This results in anaemia, low platelet counts and the production of blood cells in areas outside the bone marrow, for example in the spleen and liver, which become enlarged as a result.
Myelofibrosis is generally regarded as an incurable disease but with treatment many people can remain comfortable and symptom-free for some time. The natural course of the disease can vary considerably between individuals. In some people their disease remains stable for long periods and they are free to live a normal life with minimal interruptions from their disease or its treatment. For others, myelofibrosis progresses more quickly and people require treatment to help relieve symptoms of their disease. Transformation into acute myeloid leukaemia occurs in between 10% and 20% of cases.
Chronic neutrophilic leukaemia (CNL) is a rare MPN in which too many neutrophils (a type of white blood cell) are made in the bone marrow. These cells spill out into the circulating blood and tend to accumulate in the liver and spleen, which become enlarged as a result. CNL is usually a slowly progressing disease, closely related to another type of leukaemia called chronic myeloid leukaemia. Its natural course can vary considerably between individuals. Treatment options may include the use of chemotherapy drugs such as busulfan or hydroxyurea, which are given in tablet or capsule form. These drugs are used to control the high white cell count.
Chronic eosinophilic leukaemia (CEL)/hypereosinophilic syndrome is another rare MPN in which too many eosinophils (a type of white blood cell) are made in the bone marrow. These cells spill out of the bone marrow and accumulate in the blood and other tissues around the body. Many patients with CEL carry the FIP1L1- PDGFR alpha mutation. Some people with CEL don’t have any symptoms and the disease is picked up accidentally during a routine blood test. Others may go to their doctor because they have one or more of a range of symptoms including fever, fatigue, cough, muscle pains, pruritus (generalised itching) and diarrhoea.
CEL is a rare disease and its natural course can vary considerably between individuals. The disease may remain stable for many years, even decades, or it may quickly progress and transform to acute leukaemia. For this reason, the most appropriate treatment for each patient is decided on an individual basis.
Treatment may include corticosteroids, chemotherapy drugs such as hydroxyurea, and interferon therapy. Some patients may respond to a newer drug called imatinib mesylate (Glivec), most often used in the treatment of another type of MPN called chronic myeloid leukaemia. A stem cell transplant may be considered in selected cases.
Systemic mastocytosis or mast cell disease is a disorder that results from the overproduction of mast cells (a type of white blood cell) in the bone marrow. These cells accumulate in the blood, lymph nodes (glands), skin and other body tissues. Excess numbers of mast cells release large amounts of histamine and other substances, which can cause allergic type reactions in affected tissues. For example, when these substances collect in the skin they tend to cause an itchy rash. Other allergic-type symptoms may include abdominal pain and difficulty breathing. Over 90% of patients with systemic mastocytosis carry a mutation in the c-KIT gene.
Medications known as antihistamines are used to prevent and reduce allergic reactions. Treatment decisions tend to be made on an individual basis and may include chemotherapy in tablet form and/or interferon to help control the overproduction of mast cells in the bone marrow. Research indicates that new tyrosine kinase inhibitors may also be useful as a treatment therapy.