Myeloproliferative Neoplasms

What is Myeloproliferative Neoplasms?

Hematopoietic pluripotent stem cells are special cells that can make new versions of themselves and can create different types of blood cells. These stem cells can form either myeloid or lymphoid cells, which can further divide into various types of blood cells. These include red blood cells, lymphocytes (a type of white blood cell), granulocytes (a subtype of white blood cells), megakaryocytes (big cells that break down into platelets), and macrophages (a type of cell that helps defend our body). The process of making blood cells is controlled by the bone marrow environment, growth factors (substances that help cells grow and multiply), and transcription factors (proteins that help control which genes are activated).

If there’s abnormal growth of one or more types of myeloid cells in the blood, it can result in a group of disorders known as myeloproliferative neoplasms (MPNs). This term was first coined in 1951 but has since been updated by the World Health Organization to be called ‘myeloproliferative neoplasms’. The four main types are chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Other types also identified include chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), and unspecified MPNs. Each type of these neoplasms has its own unique traits – for example, CML is BCR-ABL1 positive, whereas PV, ET, and PMF are BCR-ABL1 negative.

The World Health Organization updated its classification for these blood and bone marrow-related disorders in 2016, thanks to advancements in the field of hematology. This helped in identifying molecular markers (substances in the body that can indicate disease) and prognostic markers (indicators that can help predict the course of a disease), and in improving our understanding of the genetic and molecular causes of these conditions.

What Causes Myeloproliferative Neoplasms?

The exact cause of MPNs (Myeloproliferative Neoplasms, a type of blood disorder) is not fully understood. However, it’s been observed that people with a specific genetic mutation (known as Janus kinase 2) often have a higher chance of developing MPNs. Also, being exposed to high levels of ionizing radiation (the energy produced by X-rays, for instance) and certain harmful substances like benzene can increase a person’s risk for these types of blood disorders.

Risk Factors and Frequency for Myeloproliferative Neoplasms

Chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis are different types of blood disorders. Each of these has different occurrence rates and are more common in certain age groups and genders.

Chronic myeloid leukemia makes up 0.5% of all new cancer cases in the United States. People aged 65 to 74 are most commonly diagnosed with this disease, with the average age of diagnosis being 65. More men than women are diagnosed with CML, with about 2.4 new men out of 100,000 and 1.4 new women out of 100,000 getting diagnosed each year. Around 67.6% of patients survive five years after diagnosis, and the average age of death is 77.
Polycythemia vera is usually diagnosed when a person is 60 years old. This disease is more common in men than women, with a male to female ratio of 1.8 to 1. Each year, 0.4 to 2.8 people out of 100,000 are diagnosed.
People are most often diagnosed with essential thrombocythemia when they are 60 years old. This disease is more common in women than men, with a male to female ratio of 1 to 2. Each year, 1 to 2.5 people out of 100,000 are diagnosed. The likelihood of being diagnosed increases as a person gets older.
Primary myelofibrosis is usually diagnosed when a person is 67 years old. Each year, 0.8 to 2.1 people out of 100,000 are diagnosed.
Other blood disorders like CNL, CEL, and unclassified MPN are very rare, so we don’t know exactly how often they occur.

Signs and Symptoms of Myeloproliferative Neoplasms

Myeloproliferative neoplasms are blood diseases that affect your body’s ability to produce blood cells. Here’s a simplified breakdown of the different types and their signs and symptoms:

Chronic myeloid leukemia (CML):

Patients may feel no symptoms with only an abnormal blood test revealing the condition
Common symptoms can include fatigue, loss of appetite, weight loss, excessive sweating, discomfort or pain in the abdomen, feeling full after eating only a small amount, easy bruising, and bleeding
Physical checks may show signs of pallor (a pale color), ecchymoses (bruises), and an enlarged liver or spleen
Rare cases may include priapism (long-lasting erections) and Sweet’s syndrome (a skin disease)

Polycythemia vera (PV):

PV is characterized by an increased number of red blood cells, which leads to thicker blood, lack of oxygen, and blood clots
Common symptoms include headaches, dizziness, vision issues, itching, fatigue, ringing in the ears, numbness or tingling, thermal discomfort, abdominal pain, loss of appetite, weight loss, bleeding, and symptoms related to blood clots
Patients may also experience itching, stinging, or burning sensations after a warm bath or shower (aquagenic pruritus)
Physical checks may reveal an enlarged liver or spleen, facial redness, superficial vein inflammation, gout, redness of the eyes, and high blood pressure

Essential thrombocythemia (ET):

ET symptoms can range from showing no signs at all to showing signs of blood clots, bleeding, and symptoms related to blood vessels
Common symptoms include a headache, dizziness, changes in vision, numbness or tingling, fatigue, and easy bruising
Patients might experience symptoms like sudden stroke due to complications related to blood clots
Physical checks may reveal enlarged spleen

Primary myelofibrosis (PMF):

Common symptoms include fatigue, night sweats, low-grade fever, feeling full after eating just a small amount, weight loss, abdominal fullness or discomfort, and bone pain
PMF is characterized by bone marrow fibrosis and abnormal blood cell production outside the bone marrow
Physical checks may reveal signs like pale skin, petechiae (tiny, pinpoint bleedings), ecchymoses (bruises), an enlarged spleen or liver, swollen lymph nodes, and symptoms related to excessive fluid in the body

Chronic neutrophilic leukemia (CNL):

Most patients may not show any symptoms, but common symptoms at the time of diagnosis can include fatigue, night sweats, loss of appetite, weight loss, easy bruising, and bone pain
Physical checks may reveal an enlarged spleen

Testing for Myeloproliferative Neoplasms

When evaluating myeloproliferative neoplasms (MPNs), these are blood diseases that affect the production of your body’s blood cells, various tests are performed including:

– Complete blood count: This is a test to check the number of different cells in your blood.
– Peripheral blood microscopic examination: This looks at a drop of your blood under a microscope.
– Comprehensive metabolic panel: A blood test to check your body’s chemical balance and metabolism.
– Electrolytes: Another blood test to check the amount of minerals in your body such as sodium and potassium.
– BCR-ABL1 test: A test to detect the specific genes causing diseases like CML, a type of leukemia.
– Leukocyte alkaline phosphatase score: This score further helps in distinguishing between the causes of high white blood cell count.
– Uric acid, LDH, EPO level test: These are blood tests that measures how your body processes purines, forms energy, and produces red blood cells, respectively.

Patients with MPNs may also have bone marrow aspiration and biopsy. This involves taking a small sample of bone marrow, usually from the hip bone, to examine it under a microscope. There might also be genetic testing to look for certain genetic mutations that cause MPNs.

Diagnosing specific types of MPNs, like chronic myeloid leukemia (CML), polycythemia vera (PV), and essential thrombocythemia (ET) requires specific criteria to be met.

CML usually involves persistent or increasing white blood cells and/or platelet count, growth of certain types of cells in the blood or bone marrow, and noticeable splenic enlargement.

PV diagnosis generally involves having a high hemoglobin count or hematocrit level, a bone marrow biopsy showing increased production of all types of blood cells, and a specific JAK2 gene mutation.

ET diagnosis typically includes a high platelet count, specific findings on a bone marrow biopsy, and ruling out other possible conditions.

For all these MPNs, the doctors take into consideration various lab results, clinical symptoms and signs, and additional genetic testing. The goal is to provide a precise diagnosis and the most suitable treatment.

Treatment Options for Myeloproliferative Neoplasms

Each type of myeloproliferative neoplasm (MPN), a group of slow-growing blood cancers, requires a different treatment approach:

Chronic myeloid leukemia (CML): CML involves a genetic mutation known as the Philadelphia chromosome, which results in abnormal enzyme activity. Medications that target this enzyme, known as tyrosine kinase inhibitors (TKIs), are used to manage CML. The disease has three stages: the chronic phase, accelerated phase, and blast phase. Medications like imatinib (first-generation TKI), nilotinib and dasatinib (second-generation TKI) are commonly used for those in the chronic phase. For those in the accelerated and blast phases, treatment often involves second-generation TKIs and potentially a stem cell transplant.

Polycythemia vera (PV): Treatment for PV depends on a patient’s age and history of clotting events. Low-risk patients, usually less than 60 years old without a history of clotting, are often managed with low dose aspirin and therapeutic phlebotomy, which helps maintain a normal volume of red blood cells. High-risk patients, generally those over 60 or with a history of clotting, are typically treated with therapeutic phlebotomy, low dose aspirin, and medications such as hydroxyurea, busulfan, or interferon alfa. If these medications aren’t effective, another medication, ruxolitinib, may be beneficial. PV can also cause uncomfortable symptoms like itchiness and burning sensations, which can often be controlled with low-dose aspirin or other medications.

Essential thrombocythemia (ET): The treatment for ET involves managing symptoms and preventing complications like bleeding and clotting. People with a high or intermediate risk (generally those over 60 or those with a particular genetic mutation that increases the risk of clotting) are typically treated with a medication known as hydroxyurea along with low-dose aspirin. Patients who are 60 or younger and don’t have a history of clotting are typically managed with low-dose aspirin or with regular check-ups.

Primary myelofibrosis (PMF): Patients with intermediate and high-risk PMF can benefit from the use of a medication known as ruxolitinib, which can help reduce spleen size and symptoms associated with PMF. A stem cell transplant may be recommended for patients with high-risk PMF as it has the potential to cure the disease. Those with low-risk disease typically only need regular observation.

Chronic neutrophilic leukemia (CNL): CNL is quite rare, so there is no specific treatment for it. Usually, these patients are managed with a medication known as hydroxyurea, which helps control the growth of blood cells.

There are several conditions related to the blood and immune system that might need to be taken into account during medical evaluations. These could include:

Chronic myelogenous leukemia
Chronic lymphocytic leukemia
Chronic myelomonocytic leukemia
Juvenile myelomonocytic leukemia
Acute myeloid leukemia
Acute lymphoblastic leukemia
Leukemoid reactions/hyperleukocytosis
Essential thrombocytosis
Secondary thrombocytosis
Juvenile myelomonocytic leukemia
Mastocytosis
Hypereosinophilic syndrome
Primary myelofibrosis
Non-Hodgkin lymphoma
Myelodysplastic syndromes
Multiple myelomas
Splenomegaly, or an enlarged spleen

What to expect with Myeloproliferative Neoplasms

The use of tyrosine kinase inhibitors, a type of cancer treatment, has greatly improved the outlook for those with Chronic Myeloid Leukemia (CML).

Patients with Essential Thrombocythemia (ET), a rare chronic blood disorder, usually have a good outlook and can expect to live a normal lifespan.

However, for patients with Triple-negative Primary Myelofibrosis (PMF), a rare bone marrow disorder, the outlook is generally worse. Moreover, according to the research done by Kampfl and his team, patients with CALR exon 9 mutations have been seen to survive longer than patients with JAK2 or MPL mutations.

Patients with Polycythemia Vera (PV) who develop Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) generally have a very poor outlook. According to a retrospective study, factors like older age (above 70 years), leukocytosis (a condition where you have too many white blood cells), and thrombosis (formation of a blood clot) can lead to a worse survival rate in patients with PV.

Possible Complications When Diagnosed with Myeloproliferative Neoplasms

The most common problems people encounter with myeloproliferative neoplasms (MPNs), a group of diseases that make the body produce too many blood cells, include blood clots and bleeding. Here is a summary of the diseases associated with MPNs and their complications:

Chronic myeloid leukemia (CML): If left untreated, CML could become more severe, a condition referred to as “blast transformation”.

Polycythemia vera (PV): This disease could lead to issues with both the arteries and veins, often resulting in blood clots and blockages (thromboembolic complications) that could cause a stroke, a pulmonary embolism, or a heart attack. There’s also a chance of severe bleeding. Some PV patients develop a bleeding disorder called acquired von Willebrand disease, especially if they are taking medication like aspirin. PV may also progress into other conditions like post-PV myelofibrosis or even acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
A condition known as erythromelalgia, causing the hands and feet to become unusually pale, red, or bluish, is a lesser-known side-effect of PV.

Essential thrombocythemia (ET): This condition results in blood clotting and bleeding issues, which could lead to a stroke, a pulmonary embolism, a heart attack, high blood pressure in the lungs (pulmonary hypertension), and a condition known as priapism which causes painful and prolonged erections.

Primary myelofibrosis (PMF): PMF could result in a variety of issues such as high blood pressure in the vein supplying the liver (portal hypertension), gastrointestinal (GI) bleeding, spinal cord compression, severe bleeding, difficulty breathing (respiratory distress), transformation to acute leukemia, blood clotting events, infections, and pulmonary hypertension.

Frequently asked questions

The prognosis for Myeloproliferative Neoplasms (MPNs) can vary depending on the specific type of MPN and individual factors. Here is a summary of the prognosis for each type of MPN: - Chronic myeloid leukemia (CML): Around 67.6% of patients survive five years after diagnosis, and the average age of death is 77. - Polycythemia vera (PV): The outlook for PV patients who develop Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) is generally poor. - Essential thrombocythemia (ET): Patients with ET usually have a good outlook and can expect to live a normal lifespan. - Primary myelofibrosis (PMF): The outlook for patients with Triple-negative PMF is generally worse, and survival may vary depending on the specific genetic mutations present. Patients with CALR exon 9 mutations have been seen to survive longer than patients with JAK2 or MPL mutations.

The exact cause of Myeloproliferative Neoplasms is not fully understood, but it has been observed that people with a specific genetic mutation (known as Janus kinase 2) often have a higher chance of developing MPNs. Additionally, being exposed to high levels of ionizing radiation and certain harmful substances like benzene can increase a person's risk for these types of blood disorders.

The signs and symptoms of Myeloproliferative Neoplasms include: - Chronic myeloid leukemia (CML): - Patients may feel no symptoms with only an abnormal blood test revealing the condition - Common symptoms can include fatigue, loss of appetite, weight loss, excessive sweating, discomfort or pain in the abdomen, feeling full after eating only a small amount, easy bruising, and bleeding - Physical checks may show signs of pallor (a pale color), ecchymoses (bruises), and an enlarged liver or spleen - Rare cases may include priapism (long-lasting erections) and Sweet's syndrome (a skin disease) - Polycythemia vera (PV): - PV is characterized by an increased number of red blood cells, which leads to thicker blood, lack of oxygen, and blood clots - Common symptoms include headaches, dizziness, vision issues, itching, fatigue, ringing in the ears, numbness or tingling, thermal discomfort, abdominal pain, loss of appetite, weight loss, bleeding, and symptoms related to blood clots - Patients may also experience itching, stinging, or burning sensations after a warm bath or shower (aquagenic pruritus) - Physical checks may reveal an enlarged liver or spleen, facial redness, superficial vein inflammation, gout, redness of the eyes, and high blood pressure - Essential thrombocythemia (ET): - ET symptoms can range from showing no signs at all to showing signs of blood clots, bleeding, and symptoms related to blood vessels - Common symptoms include a headache, dizziness, changes in vision, numbness or tingling, fatigue, and easy bruising - Patients might experience symptoms like sudden stroke due to complications related to blood clots - Physical checks may reveal an enlarged spleen - Primary myelofibrosis (PMF): - Common symptoms include fatigue, night sweats, low-grade fever, feeling full after eating just a small amount, weight loss, abdominal fullness or discomfort, and bone pain - PMF is characterized by bone marrow fibrosis and abnormal blood cell production outside the bone marrow - Physical checks may reveal signs like pale skin, petechiae (tiny, pinpoint bleedings), ecchymoses (bruises), an enlarged spleen or liver, swollen lymph nodes, and symptoms related to excessive fluid in the body - Chronic neutrophilic leukemia (CNL): - Most patients may not show any symptoms, but common symptoms at the time of diagnosis can include fatigue, night sweats, loss of appetite, weight loss, easy bruising, and bone pain - Physical checks may reveal an enlarged spleen

The types of tests needed for Myeloproliferative Neoplasms (MPNs) include: - Complete blood count - Peripheral blood microscopic examination - Comprehensive metabolic panel - Electrolytes - BCR-ABL1 test - Leukocyte alkaline phosphatase score - Uric acid, LDH, EPO level test - Bone marrow aspiration and biopsy - Genetic testing to look for certain genetic mutations that cause MPNs

The doctor needs to rule out the following conditions when diagnosing Myeloproliferative Neoplasms: - Chronic myelogenous leukemia - Chronic lymphocytic leukemia - Chronic myelomonocytic leukemia - Juvenile myelomonocytic leukemia - Acute myeloid leukemia - Acute lymphoblastic leukemia - Leukemoid reactions/hyperleukocytosis - Essential thrombocytosis - Secondary thrombocytosis - Juvenile myelomonocytic leukemia - Mastocytosis - Hypereosinophilic syndrome - Primary myelofibrosis - Non-Hodgkin lymphoma - Myelodysplastic syndromes - Multiple myelomas - Splenomegaly, or an enlarged spleen

The side effects when treating Myeloproliferative Neoplasms (MPNs) can vary depending on the specific type of MPN and the treatment being used. However, some common side effects and complications associated with MPN treatment include: - Blood clots and bleeding: MPNs can increase the risk of blood clots and bleeding, which can lead to conditions such as stroke, pulmonary embolism, heart attack, and gastrointestinal bleeding. - Thromboembolic complications: Polycythemia vera (PV) can cause issues with both arteries and veins, leading to blood clots and blockages that can result in thromboembolic complications. - Acquired von Willebrand disease: Some PV patients may develop a bleeding disorder called acquired von Willebrand disease, especially if they are taking medication like aspirin. - Erythromelalgia: PV can cause a condition known as erythromelalgia, which leads to unusual discoloration of the hands and feet. - High blood pressure: Essential thrombocythemia (ET) can cause high blood pressure in the lungs (pulmonary hypertension) and in the vein supplying the liver (portal hypertension). - Priapism: ET can also cause a condition called priapism, which leads to painful and prolonged erections. - Gastrointestinal bleeding: Primary myelofibrosis (PMF) can result in gastrointestinal bleeding. - Respiratory distress: PMF can cause difficulty breathing (respiratory distress). - Transformation to acute leukemia: PMF can progress and transform into acute leukemia. - Infections: PMF can increase the risk of infections. - Pulmonary hypertension: PMF can also lead to pulmonary hypertension. It is important to note that these side effects and complications may not occur in all patients and can vary in severity. The specific treatment plan and individual patient factors will influence the likelihood and severity of these side effects.

You should see a hematologist or an oncologist for Myeloproliferative Neoplasms.

Myeloproliferative Neoplasms (MPNs) are treated differently depending on the specific type of MPN. The treatment approaches for each type are as follows: 1. Chronic myeloid leukemia (CML): CML is managed with medications called tyrosine kinase inhibitors (TKIs) that target the abnormal enzyme activity caused by the genetic mutation known as the Philadelphia chromosome. Different TKIs, such as imatinib, nilotinib, and dasatinib, are used depending on the stage of the disease. 2. Polycythemia vera (PV): Treatment for PV depends on the patient's age and history of clotting events. Low-risk patients are often managed with low-dose aspirin and therapeutic phlebotomy. High-risk patients are typically treated with therapeutic phlebotomy, low-dose aspirin, and medications like hydroxyurea, busulfan, or interferon alfa. 3. Essential thrombocythemia (ET): Treatment for ET involves managing symptoms and preventing complications like bleeding and clotting. High or intermediate-risk patients are typically treated with hydroxyurea and low-dose aspirin. Low-risk patients are managed with low-dose aspirin or regular check-ups. 4. Primary myelofibrosis (PMF): Intermediate and high-risk PMF patients can benefit from a medication called ruxolitinib, which reduces spleen size and associated symptoms. A stem cell transplant may be recommended for high-risk PMF patients. Low-risk PMF patients usually only require regular observation. 5. Chronic neutrophilic leukemia (CNL): There is no specific treatment for CNL due to its rarity. Patients with CNL are typically managed with hydroxyurea to control the growth of blood cells.

Myeloproliferative Neoplasms (MPNs) are a group of disorders characterized by abnormal growth of one or more types of myeloid cells in the blood. The four main types of MPNs are chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Other types include chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), and unspecified MPNs.

Blood Disorders Leukemia & Lymphoma Myeloid