Myeloproliferative neoplasms (MPNs) are a group of rare, chronic blood cancers in which the patient’s bone marrow produces abnormal blood cells. This can cause a host of symptoms and complications. As these conditions are chronic in nature, they can last for a long period of time. They are are also progressive in nature and may worsen over time.
MPNs can be classified according to the absence of presence of a chromosomal abnormality called the Philadelphia chromosome. Philadelphia chromosome negative MPNs include Polycythaemia Vera (PV), Essential Thrombocythaemia (ET) and Myelofibrosis (MF).
Polycythaemia Vera (PV)
PV is a rare, chronic blood disease in which a person’s body makes too many red blood cells. This may also be accompanied by too many white blood cells and/or platelets. Too many red blood cells can cause the blood to be too viscous and block the flow of the blood through arteries and veins. This can result in a heart attack or stroke.
The main cause of PV is a genetic mutation in the Janus Kinase 2 (JAK2) gene.
What are the signs and symptoms?
Signs and symptoms of PV may include:
- Shortness of breath
- Abdominal pain/ discomfort
- Early feeling of fullness when eating
- Pain under the left ribs
- Day or night sweats
- Problems concentrating
- Numbness in hands/ feet
- Dizziness, vertigo, light headedness
- Insomnia
- Headache
- Double or blurred vision
- Itching
- Reddening of the face or burning sensation on the skin
- Bone pain
- Fatigue
- Ringing in ears
- Enlarged spleen
Other serious complications from PV may include:
- Blood clots leading to a heart attack or stroke
- Stomach ulcers, gout or kidney stones
- Chest pain
- Progression to leukaemia
- Progression to another MPN ( MF)
What is the prognosis for patients with PV?
PV patients have an excellent chance at longevity if monitored and treated properly.
What is the risk of progression to an acute leukaemia?
Leukaemic transformation rates at 20 years are estimated to be < 10% for PV patients.
What is the risk of progression to MF?
About 15% of patients with PV progress to MF.
Essential Thrombocythaemia (ET)
ET is a rare blood disease in which a person’s body generates too many platelets. These platelets may not function appropriately and cause a blockage in blood vessels ( thrombosis), or less commonly, bleeding problems.
The cause of ET is not fully understood but 3 specific mutations have been identified in patients with ET. These mutations are the Janus Kinase 2 (JAK2), Calreticulin ( CALR) and mutation of the thrombopoietin receptor ( MPL).
What are the signs and symptoms?
Some patients are asymptomatic whilst others may exhibit any of these symptoms:
- Itching
- Night sweats
- Fatigue/weakness
- Burning or throbbing hands or feet
- Headaches
- Dizziness
- Blood clots
- Enlarged spleen
Serious complications from ET may include:
- Clotting complications
- Pregnancy complications
- Excessive bleeding
- Stroke
- Heart attack
- Progression to another MPN, such as myelofibrosis (MF)
- Progression to acute leukaemia
What is the prognosis for patients with ET?
ET patients have an excellent chance at longevity if monitored and treated properly.
What is the risk of progression to MF?
About 15% of ET patients may progress to MF.
What is the risk of progression to an acute leukaemia?
Leukaemic transformation rates at 20 years are estimated to be about 5% for ET patients.
Myelofibrosis (MF)
MF is a chronic blood cancer in which scar tissue forms in the bone marrow and reduces its ability to produce normal blood cells. It may be associated with certain genetic mutations such as the Janus Kinase 2 (JAK2) mutation. In MF, the scarring of the bone marrow leads to reduced production of normal blood cells.
What are the signs and symptoms?
Some patients may not experience any symptoms whilst others may exhibit the following symptoms:
- Fatigue
- Night sweats
- Bone/ muscle pain
- Itching
- Abdominal pain
- Gout
- Enlarged spleen leading to pain under the left rib or early feeling of fullness
Other complications from MF may include:
- Heart attack or stroke
- Infections
- Increased pressure on blood flow to the liver ( portal hypertension)
- Bleeding complications
- Progression to leukaemia
What is the prognosis for patients with MF?
The prognosis of MF is different for every patient. While some live for many years without developing major symptoms or complications, others may find that their disease progresses more quickly.
Factors that influence MF prognosis are age, white blood cell counts, number of immature white blood cells ( also known as blasts or leukaemic cells) in the blood, constitutional symptoms ( e.g night sweats, weight loss, fever), low red blood cells, transfusion dependence, low platelet count and abnormal chromosomal analysis.
Your doctor will need to monitor you closely and will discuss your individual prognosis based on the relevant factors.
What is the risk of progression to an acute leukaemia?
10 year risk of transformation to an acute leukaemia is approximately 20% for MF patients.
If you experience any of the symptoms mentioned above or suspected to have an underlying MPN from your routine blood tests, your doctor will need to perform more tests to confirm the diagnosis. The diagnostic work up will include:
- Thorough personal and medical history
- Physical examination - Your doctor will check for the presence of any enlarged liver or spleen.
- Blood tests - Routine blood test such as a full blood count is required to determine the number of white blood cells, red blood cells and platelets. Specialised tests (e.g molecular tests) may be required depending on the suspected MPN.
- Biopsy - A bone marrow aspirate or biopsy may be required to confirm the diagnosis. Your doctor will advice you accordingly.
There are various treatment options available depending on the underlying MPN and associated symptoms. These may include:
Transfusion with Various Blood Products
Patients with MF can be given red blood cells and platelet transfusions when they become symptomatic due to low blood counts.
Venesection
This refers to the removal of blood from patients with PV to achieve a haematocrit target of <45%. Your doctor will decide the frequency and need for venesection based on your blood tests.
Antiplatelet Therapy
Patients with PV and ET will be started on antiplatelet therapy (e.g aspirin) to reduce the risk of blood clots. Those who are allergic or intolerant to aspirin can be switched to an alternative antiplatelet therapy, such as clopidogrel.
Cytoreductive Therapy
Patients with PV and ET who are deemed high risk for clotting ( e.g age above 60 years old with a previous history of blood clots) may also require cytoreductive therapy in addition to other therapies. First line treatment includes the use of hydroxyurea.
Those who are allergic or intolerant of hydroxyurea may be switched to an alternative agent, such as anagrelide.
Patients who are pregnant may be started on an alternative agent, such as Interferon (usually pegylated form) because it has been shown to non-teratogenic (i.e does not cause birth defects).
Targeted Therapy
Ruxolitinib (Jakavi) is the first drug approved by the FDA for the treatment of MF patients. It is a Jak 1/Jak 2 inhibitor and is used for the treatment of patients with intermediate or high risk MF, including primary MF, post polycythaemia vera MF and post essential thrombocythaemia MF as a targeted therapy.
Ruxolitininb has also been approved recently for the treatment of PV patients who have an inadequate response to or are intolerant to hydroxyurea.
Stem Cell Transplant
Allogeneic stem cell transplantation (ASCT) is the only curative treatment for MF. Patients need to discuss with their doctor whether or not they may be eligible for such a procedure and what are the risks involved, given the complexity of the procedure and associated complications. With ASCT, blood forming stem cells are transferred from a donor to the patient. The patient received chemotherapy and/or radiation therapy to eradicate the diseased bone marrow. The decision to pursue ASCT should be made in close consultation with your doctor and a transplant physician.
