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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).
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.
Signs and symptoms of PV may include:
PV patients have an excellent chance at longevity if monitored and treated properly.
Leukaemic transformation rates at 20 years are estimated to be < 10% for PV patients.
About 15% of patients with PV progress to MF.
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).
Some patients are asymptomatic whilst others may exhibit any of these symptoms:
ET patients have an excellent chance at longevity if monitored and treated properly.
About 15% of ET patients may progress to MF.
Leukaemic transformation rates at 20 years are estimated to be about 5% for ET patients.
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.
Some patients may not experience any symptoms whilst others may exhibit the following symptoms:
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.
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:
There are various treatment options available depending on the underlying MPN and associated symptoms. These may include:
Patients with MF can be given red blood cells and platelet transfusions when they become symptomatic due to low blood counts.
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.
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.
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).
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.