Myeloproliferative neoplasms (MPNs) are a rare group of cancers that develop from bone marrowsoft, spongy tissue found in bones that makes blood cells, the spongey, soft tissuetissue/the material that joins, holds up or surrounds inside body parts such as fat, muscle, ligaments and lining around joints found in the centre of most bones. Bone marrow is primarily responsible for the production of bloodthe red bodily fluid that transports oxygen and other nutrients around the body cellsthe basic structural and functional unit of all living things in the body.
Blood is the bodily fluid of the circulatory system that provides nutrients and oxygen to our tissues, and helps remove waste from our bodies. There are three primary types of blood cells produced in bone marrow stem cells (immature blood cells). Red blood cells (RBCs), or erythrocytes, are responsible for providing oxygen to the tissues in our body, as well as transporting carbon dioxide to the lungs to be exhaled. White blood cells (WBCs) are responsible for fighting infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body and disease in the body. Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding are blood cells that play a major role in blood clotting (or coagulation), which is an important process that helps reduce blood loss after an injury. MPNs cause the bone marrow to produce too much of one or more of these cells, which changes the thickness of the blood and the effectiveness of these cells.
MPNs are usually more common in people over 50 years old, however anyone can develop this disease at any age. The prevalence of MPNs in the sexes vary by subtype.
Types of Myeloproliferative Neoplasms
There are several types of MPNs, some of which may transform into other types of MPN or acutenew, recent, comes with an urgent or significant sense, is sudden, sharp myeloid leukaemiacancer of blood and/or blood forming tissues if left untreated. Three of the seven types of MPNs are most common, with the other four being incredibly rare.
Polycythaemia (Rubra) Vera (PV)
Polycythaemia rubra vera (PV) is a common type of MPN caused by an overproduction of RBCs in bone marrow. These excess RBCs cause the blood to thicken, which can slow blood flow and cause serious problems, such as clots in blood vessels and high blood pressure. Excess RBCs can also crowd the bone marrow (causing abnormal levels of other blood cells), spleen (causing splenomegalyenlargement of the spleen) and/or the liver (causing hepatomegalyenlargement of the liver). This disease is often more prevalent in men, is often manageable, and can have a good prognosisto predict how a disease/condition may progress and what the outcome might be.
Essential Thrombocythemia
Essential thrombocytosis is a common MPN caused by an overproduction of platelets in bone marrow. Excess platelets may cause abnormal blood clotting, which can block blood flow throughout the body. It may also cause abnormal bleeding and issues with fetal development. This disease affects the sexes equally, is often manageable, and can have a good prognosis.
Myelofibrosis
Myelofibrosis, also known as primary myelofibrosis and idiopathic myelofibrosis, is a common MPN caused by an over-stimulation of specialised cells in the bone marrow called fibroblasts. Fibroblasts are responsible for the production of collagen and extra-cellular matrix in connective tissuea group of cells that work together to perform a function, such as bone. When over-stimulated, these cells produce an overgrowth of thick and coarse fibres in the bone marrow, which inhibit the production of RBCs, WBCs, and platelets. This ultimately leads to progressive bone marrow failure, as well as other potentially severe complications in the body. Myelofibrosis can be manageable, and may have a good prognosis.
Chronic Neutrophilic Leukaemia (CNL)
Chronica long-lasting disease that changes slowly over time neutrophilic leukaemia (CNL) is a very rare type of MPN that is caused by an overproduction of a specific WBC, called a neutrophil. Neutrophilsa type of white blood cell that act as a first responder to infections in the body are the most abundant WBC, and are responsible for aggressively killing foreign material (such as bacteria and viruses) in the body. CNL affects the sexes equally, is often aggressive, and may not have as good of a prognosis as other MPNs.
Chronic Eosinophilic Leukaemia (CEL)
Chronic eosinophilic leukaemia (CEL) is a very rare type of MPN that is caused by an overproduction of a specific WBC, called an eosinophil. Eosinophils comprise a very small portion of WBCs, and are responsible for the destruction of parasites, inflammatory chemicals, and allergens in the body. CEL is often aggressive, and may not have as good of a prognosis as other MPNs.
Chronic Myeloid Leukaemia (CML)
Chronic myeloid leukaemia (CML) is a rare type of MPN that is caused by an overproduction of immature WBCs. These excess cells can crowd the bone marrow, interfering with regular cell production. They can also be released from the bone marrow and circulate in the blood stream, however as they are immature, they would be ineffective in fighting disease. CML is more common in males, can become aggressive, and can have a good prognosis.
For more information on CML, please refer to the Rare Cancers Australia Chronic Myeloid Leukaemia (CML) page.
Unclassifiable MPNs
Unclassifiable MPNs are cancers that have features of MPNs, but don’t fit into any subtype. Symptoms and treatments will vary based on the patient’s cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs characteristics.
Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are a group of blood cancers that have characteristics of both MDS and MPN. Symptoms and treatments will vary based on the patient’s cancer characteristics.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, because of how rare MPNs are, there is currently no standard staging and grading system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- The type of MPN you have.
- Whether or not the cancer has metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumoura tissue mass that forms from groups of unhealthy cells DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for MPNs may include:
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Plateletpheresisremoval of excess platelets from the blood.
- Transfusion therapya procedure where blood or blood components are transferred into your bloodstream.
- Venesectioncontrolled removal of blood to reduce excess blood levels rapidly.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Cytoreductive medicationmedication used to reduce levels of red blood cells, white blood cells and platelets in the blood when they are abnormally high, potentially including hydroxycarbamide (hydroxyurea).
- Antiplatelet therapymedication used to prevent blood clotting, potentially including aspirin.
- Immunotherapya treatment that uses a person's immune system to fight cancer, potentially including interferons.
- Targeted therapymedication that targets specific molecular features of cancer cells, potentially including protein kinase inhibitors such as:
- JAK2 inhibitors.
- Tyrosine protein inhibitors.
- Ruxolitinib.
- Imatinib.
- Anagrelide.
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including a splenectomyremoval of the spleen.
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Complementary therapiesa variety of practices and exercises used alongside conventional treatment methods that may improve wellbeing and sense of control (e.g. meditation, art therapy, yoga etc.).
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.
Risk factors
While the cause of MPNs remain unknown, the following factors may increase your riskthe possibility that something bad will happen of developing this disease:
- Genetic mutations, potentially including:
- JAK2 (janus kinase 2) gene.
- CALR (calreticulin) 1 or 2 gene/s.
- MPL (myeloproliferative leukemia protein, also known as the thrombopoietin receptor gene) genes.
- Increased age.
- Long-term exposure to high levels of benzene and/or radiation.
- Family history (uncommon).
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Symptoms
The symptoms MPNs may vary by the type you have. Many MPNs have no symptoms in the early stages of the disease, but may develop symptoms over time.
General MPN Symptoms
General symptoms of all MPNs may include:
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Unexplained weakness.
- Unexplained weight loss.
- Fever.
- Itchy skin.
- Night sweats.
- Unexplained pain in bones and/or joints.
- Splenomegaly.
- Hepatomegaly.
Symptoms of PRV
Patients with PRV may experience the following symptoms in addition to general MPN symptoms:
- Headaches.
- Blurred vision.
- Dizziness.
- Gout.
- A ruddy (red) complexation.
- Reddening of the palms of the hands and soles of the feet.
- Buring pain in extremities (erythromelalgia).
- Easy bruising and/or bleeding.
Symptoms of ET
Patients with ET may experience the following symptoms in addition to general MPN symptoms:
- Tingling and/or burning in the hands and feet.
- Headache.
- Changes in vision.
- Dizziness.
Symptoms of Myelofibrosis
Patients with myelofibrosis may experience the following symptoms in addition to general MPN symptoms:
- Anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection.
- Paleness.
- Dyspneadifficulty breathing, shortness of breath.
- Heart palpitations.
- Easy bruising and/or bleeding.
- Flushed face.
Symptoms of CNL
Patients with CNL may experience easy bruising in addition to general MPN symptoms.
Symptoms of CEL
Patients with CEL may experience the following symptoms in addition to general MPN symptoms:
- Persistent cough.
- Abnormal swelling around the eyes, lips, hands, feet and/or throat.
- Muscle pain.
- Diarrhoeafrequent discharge of watery or loose stools from the body.
Symptoms of CML
Patients with CML may experience the following symptoms in addition to general MPN symptoms:
- Anaemia.
- Dizziness.
- Paleness.
- Dyspnea.
- Easy bruising and/or bleeding.
- Persistent infections.
- Abdominal discomfort or pain, especially on the upper left side.
- Excessive sweating.
Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned.
Some information regarding symptoms was obtained from the Myeloproliferative Neoplasms page published by the National Cancer Institute.
Diagnosis
If your doctor suspects you have an MPN, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow..
- Biopsyremoval of a section of tissue to analyse for cancer cells.
