Myeloproliferative neoplasms (MPNs) are a rare group of cancers that develop from bone marrow, the spongey, soft tissue found in the centre of most bones. Bone marrow is primarily responsible for the production of blood cells 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 infection and disease in the body. Platelets 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 acute myeloid leukaemia 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 splenomegaly) and/or the liver (causing hepatomegaly). This disease is often more prevalent in men, is often manageable, and can have a good prognosis.
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 tissue, 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)
Chronic neutrophilic leukaemia (CNL) is a very rare type of MPN that is caused by an overproduction of a specific WBC, called a neutrophil. Neutrophils 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 cancer 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, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging 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 testing, which analyses your tumour 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 wait.
- Plateletpheresis (removal of excess platelets from the blood).
- Transfusion therapy (adding RBCs, WBCs and/or platelets to your blood).
- Venesection/phlebotomy (controlled removal of blood to reduce excess blood levels rapidly).
- Chemotherapy.
- Radiation therapy.
- Cytoreductive therapy, potentially including hydroxycarbamide (hydroxyurea).
- Antiplatelet therapy, potentially including aspirin.
- Immunotherapy, potentially including interferons.
- Targeted therapy, potentially including protein kinase inhibitors such as:
- JAK2 inhibitors.
- Tyrosine protein inhibitors.
- Ruxolitinib.
- Imatinib.
- Anagrelide.
- Surgery, potentially including a splenectomy (removal of the spleen).
- Stem cell transplant.
- Clinical trials.
- Complementary therapies.
- Palliative care.
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 risk 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.
Early 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:
- Fatigue.
- Unexplained weakness.
- Unexplained weight loss.
- Fever.
- Itchy skin.
- Night sweats.
- Unexplained pain in bones and/or joints.
- Enlarged spleen (splenomegaly).
- Enlarged liver (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:
- Anaemia.
- Paleness.
- 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.
- Diarrhoea.
Symptoms of CML
Patients with CML may experience the following symptoms in addition to general MPN symptoms:
- Anaemia.
- Dizziness.
- Paleness.
- Shortness of breath.
- 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/diagnosing
If your doctor suspects you have an MPN, they will order a range of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Blood tests
Your doctor will recommend a blood test for check for signs of an MPN. The most common test is a full blood count (FBC), which will analyse the levels of red blood cells, white blood cells and platelets in the blood. Low counts or abnormal cellular appearance in any of these categories could be indicative of disease.
Your doctor may also perform blood chemistry tests, which analyse the levels of certain chemicals in your body. The blood required for these tests will often be taken at the same time as the FBC. Some of the substances that they may examine include:
- Iron.
- Specific genes to check for mutations, most commonly including:
- JAK2 gene.
- CALR gene.
- MPL gene.
- Liver function test (LFT).
- Uric acid.
- Lactate dehydrogenase (LDH).
Imaging
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-ray and/or positron emission tomography (PET scan), to check for signs of metastasis.
Bone marrow biopsy
Once the location of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. In most cases, this will be done by a bone marrow aspiration and biopsy. This process involves inserting the needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for cancer cells.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage MPNs have a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.