MPNs - The Condition
Myeloproliferative neoplasms (MPNs) are a group of blood cancers characterized by the overproduction of blood cells in the bone marrow. They include conditions like polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPNs result from genetic mutations in hematopoietic stem cells, leading to abnormal blood cell proliferation. These disorders can cause symptoms such as fatigue, bleeding, and an increased risk of blood clots. MPNs are chronic conditions that require ongoing management, often with medications or therapeutic procedures.
Polycythemia vera (PV)
Polycythemia vera (PV) is a type of myeloproliferative neoplasm (MPN), a blood cancer characterized by the overproduction of red blood cells in the bone marrow. This excess of red blood cells leads to thickened blood, which can increase the risk of blood clots, heart attacks, and strokes. PV is usually caused by a mutation in the JAK2 gene, which promotes uncontrolled cell growth. Symptoms may include headaches, dizziness, fatigue, itching, and an enlarged spleen. Treatment often involves blood-thinning medications, phlebotomy, and targeted therapies to manage symptoms and reduce risks.
Essential thrombocythemia (ET)
Essential thrombocythemia (ET) is a type of myeloproliferative neoplasm (MPN), a blood disorder characterized by the overproduction of platelets in the bone marrow. This condition is often caused by mutations in the JAK2, CALR, or MPL genes. The excessive platelets increase the risk of blood clots, which can lead to complications like stroke, heart attack, or deep vein thrombosis. Symptoms of ET may include headaches, dizziness, and tingling in the hands and feet. Treatment focuses on reducing platelet counts and managing symptoms to prevent complications.
Primary myelofibrosis (PMF)
Primary myelofibrosis (PMF) is a type of myeloproliferative neoplasm (MPN) characterized by the excessive production of abnormal blood cells, leading to scarring (fibrosis) in the bone marrow. This scarring disrupts normal blood cell production, causing anemia, fatigue, and an enlarged spleen (splenomegaly). PMF is often associated with mutations in genes like JAK2, CALR, or MPL. Symptoms can include weakness, night sweats, and weight loss. Treatment focuses on managing symptoms and may include medications, blood transfusions, or bone marrow transplantation in severe cases.
Symptoms and Diagnosis
Polycythemia Vera (PV)
Symptoms: Polycythemia vera is marked by an overproduction of red blood cells, leading to thickened blood and increased risks of clotting events like deep vein thrombosis, stroke, and heart attack. Common symptoms include headaches, dizziness, blurred vision, and a ruddy complexion. Patients may also experience fatigue, itching (especially after a hot shower), and a feeling of fullness in the abdomen due to an enlarged spleen (splenomegaly).
Diagnosis: Diagnosis typically begins with a complete blood count (CBC) showing elevated red blood cell counts, hematocrit, and hemoglobin levels. Bone marrow biopsy and genetic testing, particularly for the JAK2 mutation, are crucial in confirming the diagnosis. Erythropoietin levels are usually low in PV, distinguishing it from other causes of increased red blood cells. Additional tests might include ultrasound to check for spleen size and blood tests to monitor for complications like high uric acid levels.
Essential Thrombocythemia (ET)
Symptoms: Essential thrombocythemia is characterized by an excessive number of platelets, increasing the risk of abnormal clotting and bleeding. Common symptoms include headaches, dizziness, and visual disturbances. Some patients may experience burning or tingling sensations in their hands and feet (erythromelalgia) or even transient ischemic attacks (mini-strokes). In some cases, patients may be asymptomatic and diagnosed incidentally during routine blood tests.
Diagnosis: Diagnosis often starts with a CBC showing elevated platelet counts. Genetic testing for mutations in JAK2, CALR, or MPL is essential for confirming ET. A bone marrow biopsy may be performed to rule out other myeloproliferative disorders, showing increased megakaryocytes. Testing for iron levels, erythropoietin levels, and checking for secondary causes of thrombocytosis are also part of the diagnostic process. Regular monitoring is crucial to manage the risk of thrombotic events.
Primary Myelofibrosis (PMF)
Symptoms: Primary myelofibrosis is characterized by progressive bone marrow fibrosis, leading to symptoms like severe fatigue, anemia, and splenomegaly. Patients often experience unintentional weight loss, night sweats, and bone pain. As the disease progresses, extramedullary hematopoiesis (blood cell production outside the bone marrow) can occur, causing further complications like portal hypertension or liver dysfunction.
Diagnosis: PMF diagnosis involves a CBC revealing anemia and immature blood cells (leukoerythroblastosis), along with a bone marrow biopsy showing fibrosis and abnormal megakaryocytes. Genetic testing for mutations in JAK2, CALR, or MPL helps confirm the diagnosis. Additional imaging, like ultrasound or MRI, may assess spleen and liver enlargement. Prognostic scoring systems, like the DIPSS, are often used to determine disease severity and guide treatment decisions.
Treatement Options
Treatment of MPN is currently geared toward relieving symptoms and preventing complications. Your doctor will base your treatment plan on the type of MPN you have and the severity of your symptoms.
Some people with MPN experience no major health changes for several years. For those who do require treatment, options include bone marrow transplant, phlebotomy (blood letting), and medications that reduce blood clotting or lower blood cell count. Chemotherapy or radiation may also be recommended if the MPN progresses to acute myeloid leukemia.
Many patients with MPN receive treatment through clinical trials, which offer access to the latest therapies. Your doctor can help you to determine whether you are eligible to take part in a clinical trial and whether it’s the right option for you.
1. Polycythemia Vera (PV) Treatment: Treatment of Polycythemia Vera primarily aims to reduce the risk of thrombosis by controlling hematocrit levels and alleviating symptoms. Phlebotomy is often the first-line treatment, where blood is regularly removed to decrease red blood cell mass and maintain hematocrit levels below 45%. Low-dose aspirin is commonly prescribed to reduce the risk of clotting. In cases where phlebotomy alone is insufficient, or for patients at high risk of thrombosis, cytoreductive therapies such as hydroxyurea or interferon-alpha may be used to control blood cell production.
2. Essential Thrombocythemia (ET) Treatment: The treatment of Essential Thrombocythemia focuses on preventing thrombotic events and managing symptoms. Low-risk patients may be managed with low-dose aspirin to reduce the risk of clotting. For high-risk patients, or those with symptomatic disease, cytoreductive therapy with agents like hydroxyurea, anagrelide, or interferon-alpha is recommended to lower platelet counts. Regular monitoring of platelet levels and adjustment of treatment is necessary to balance the prevention of thrombotic and hemorrhagic complications.
3. Primary Myelofibrosis (PMF) Treatment: Primary Myelofibrosis treatment is complex and depends on disease severity and patient symptoms. Symptomatic anemia may be managed with erythropoiesis-stimulating agents or transfusions. For splenomegaly or symptomatic disease, JAK inhibitors like ruxolitinib are often used to reduce spleen size and improve quality of life. In advanced cases, allogeneic stem cell transplantation may be considered, particularly for younger patients or those with high-risk disease, offering the potential for cure but with significant associated risks.
4. Managing Thrombotic Risks: Across all MPNs, managing thrombotic risk is crucial due to the elevated risk of blood clots. In addition to specific treatments like phlebotomy for PV and cytoreductive therapy for ET, lifestyle modifications such as smoking cessation, maintaining a healthy weight, and regular exercise are advised. Low-dose aspirin is widely used to reduce thrombotic risk, and in some cases, anticoagulants may be prescribed for patients with a history of thrombosis or significant risk factors.
5. Monitoring and Follow-up: Regular monitoring is essential for managing MPNs effectively. This includes periodic complete blood counts (CBC), assessment of spleen size, and monitoring for potential complications like transformation to myelofibrosis or acute leukemia. Patients on cytoreductive therapies require regular follow-up to adjust dosages and monitor for side effects. Genetic testing may also be part of ongoing management, particularly in PMF, where JAK2, CALR, and MPL mutation status can influence treatment decisions.
6. Patient Support and Quality of Life: Managing MPNs also involves addressing quality of life issues. Patients may experience symptoms like fatigue, itching, or bone pain that impact daily life. Supportive care, including addressing psychological aspects, is important. Patients should be educated about their condition, treatment options, and potential side effects to make informed decisions about their care. Regular communication with healthcare providers, involvement in patient support groups, and access to educational resources are vital components of comprehensive MPN management.
Publications
PRECISION: Canadian guidelines for polycythemia vera (PV) management
PRECISION, a national program designed to assess management of PV in Canadian daily practice, has published a series of recommendations on PV management
English: PRECISION: A Canadian In-practice Needs Assessment in Management of PV in Canada
Clin Lymphoma Myeloma Leuk. 2015 Aug 7. pii: S2152-2650(15)01098-8.
Videos
Stem Cell Transplant for Myelofibrosis in the JAK2 Inhibitor Era
Dr. Vikas Gupta of the Princess Margaret Cancer Centre in Toronto speaks at the U.S. Focus on Myeloproliferative Neoplasms and Myelodysplastic Syndromes 2015 conference in Alexandria, VA.
Transplant Timing for Myelofibrosis in the Era of JAK2 inhibitors
Dr. Vikas Gupta of the Princess Margaret Cancer Centre in Toronto and Dr. Rami S. Komrokji of the Moffitt Cancer Center in Tampa discuss their individual approaches that consider patient wishes and goals, type of donor, and disease risk in their decisions to perform stem cell transplants upfront or to delay them until after JAK2 inhibitor therapy.
Princess Margaret Cancer Centre – Dr. Vikas Gupta
Dr. Vikas Gupta talks about how the generous funding received from Elizabeth and Tony Comper will enable Princess Margaret Cancer Centre to develop a world-class program for the treatment of myeloproliferative neoplasms (MPNs)—a rare type of blood cancer. September 25, 2015.
Presentation Support
What’s New in the Treatment of Myeloproliferative Neoplasms
Dr. Vikas Gupta, invited speaker, Queen’s University, Kingston, Ontario. November 3, 2015.
Dr. Shireen Sirhan. Addressing the Canadian MPN National Advisory Group, Vancouver, British Columbia. October 2, 2015.
Which Myelofibrosis Patients are Candidates for Upfront Stem Cell Transplantation?
Dr. Vikas Gupta, invited speaker, SOHO 2015 Annual Meeting (Society of Hematologic Oncology), Houston, Texas. September 2015.
Online Support
With 12,000+ monthly readers, MPNforum is the most widely followed independent international online monthly magazine focused on myeloproliferative neoplasm patients and caregivers. The magazine, and its companion MPN Quarterly Journal, are open source publications entirely managed and staffed by patients and caregivers with the volunteer participation of scientists, hematologists and healthcare providers.
MPN Updates for iPhone®, iPad® and iPod Touch® is an interactive digital publication that focuses on the diagnosis and treatment of MPN disease states. The easy-to-read, digital flipbook format provides awareness of emerging therapeutic agents and their impact on patient outcomes. This newsletter is sponsored by Incyte Corp. through a third-party independent grant.
An independent newspaper that provides timely and relevant news and commentary about clinical developments in the field of hematology.
Clinical Tools
The MPN eSIMPLE app provides data, resources, and guidance to assist Canadian physicians in their daily management of patients with myeloproliferative neoplasm (MPNs).
The goal is to guide physicians in selecting the most appropriate therapeutic approach for each of their MPN patients and to standardize management strategies across the country.
The app can be used using the MPN eSIMPLE website or downloaded