For Patients

Here’s some informational content for you to browse and learn more about Myeloproliferative Neoplasms.

What are myeloproliferative neoplasms?

“Myelo” is the Greek word for marrow

“Proliferative” means growing or reproducing

“Neoplasm” is the abnormal or improper growth of  cells or tissue

MPN refers to abnormal or improper functioning of the bone marrow organ.

Bone marrow is the body’s blood-forming (hematopoeitic) organ. It contains blood-forming cells called “hematopoeitic precursor or stem cells” that have two important functions:

  • self-renewal to maintain a pool of stem cells for future proliferation or growth
  • ability to mature into adult blood cells that will leave the marrow and enter the circulation.

These precursor cells produce several types of blood cells; red blood cells (RBC), white blood cells (WBC) and platelets. Because of this versatility, they are called “pluripotential hematopoeitic precursor cells (“PHPC”). Each PHPC is a stem cell that can reproduce itself (clone) as well as produce a number of daughter cells (blasts). Normal bone marrow is composed of a family of hematopoeitic clones all reproducing themselves and forming daughter cells that will, in turn, develop into red blood cells, white blood cells and platelets. The dedicated daughter cells divide over and over again and it is their growth that fills the marrow with the diverse types of immature and developing blood cells that are seen in a normal bone marrow specimen. The normal marrow also balances production of different cell types so that they appear in the blood in their proper proportions.

In MPN, one abnormal PHPC clone has a growth advantage that allows it to overgrow at the expense of the normal PHPC clones. While this PHPC clone is “abnormal”, it is still able to self-renew and to produce several types of blood cells. The cells produced by the abnormal clone may be difficult to distinguish from those produced by normal cells.

In myeloproliferative neoplasm, we do find an abnormal over or under production of a particular cell type. Thus MPN involves the improper balance between production of different blood cell types and it involves abnormality of any given blood cell type.

MPN includes chronic myeloid leukemia (CML), Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Idiopathic or Primary Myelofibrosis (PMF), as well as, post-ET and post-PV myelofibrosis. In spite of their often insidious clinical onset, each of the MPN has the potential to undergo clonal evolution and a stepwise progression that terminates in bone marrow failure due to myelofibrosis, ineffective haematopoiesis (the forming of new blood cells) or transformation to acute leukemia.

The BCR/ABL fusion gene, which is made up of hereditary material in humans (DNA), has served as a diagnostic tool to distinguish chronic myeloid leukemia from the other MPD. The Philadelphia negative (Ph-) MPN (Polycythemia Vera, Myelofibrosis, Essential Thrombocythemia) are complicated by an overlap of clinical, laboratory and morphological findings, which compromise our ability to distinguish these specific disease entities. Leukocytosis, thrombocytosis, megakaryocytic hyperplasia, splenomegaly (enlarged spleen) and myelofibrosis are all features that can occur in Polycythemia Vera, Idiopathic Myelofibrosis, or Essential Thrombocythemia, making precise diagnosis of the individual patient difficult. In addition, the clinical course of Polycythemia Vera and Essential Thrombocythemia is complicated by an extraordinarily high occurrence of blood clotting disorders, which are the leading causes of illness and death.

Treatment of Polycythemia Vera and Essential Thrombocythemia has been directed toward normalization of the patient’s blood counts with the hope of reducing the occurrence of such fatal blood clotting (thrombotic) events. The hematological parameters that might serve as the endpoints for such therapeutic interventions have not been well defined, leading to considerable debate about guidelines for the optimal approach for the treatment of each of these disorders. By contrast, Myelofibrosis is associated with a much graver prognosis and no disease altering therapeutic intervention besides allogeneic Stem Cell Transplantation (SCT) has been associated with alteration of the natural history of this form of MPN.

How common are the diseases

MPNs are classified as orphan diseases (an orphan disease is defined by the National Institute of Health as any disease that affects less than 200,000 people in the United States at any given time). Because of the small populations affected by these diseases, pharmaceutical companies and biotech companies rarely pursue treatments.

The actual number of newly diagnosed patients with an MPN per year (incidence) is difficult to measure since many people affected are asymptomatic until the occurrence of a major consequence such as a formation of a solid blood clot in an arterial or venous vessel (thrombosis) or stroke. Even then, incidence of the disease may be undiagnosed and therefore uncounted. MPN statistics are not even measured by SEER (Surveillance, Epidemiology, and End Results Program of the National Cancer Institute), the most authoritative source of information on cancer incidence and survival in the United States, even though the incidence of these diseases matches or exceeds other measured cancers such as Multiple Myeloma and Chronic Myeloid Leukemia.

The most complete statistics to date on MPN incidence come from a Swedish study in 2001, which shows the following:

Incidence of Myeloproliferative Neoplasms Annual Incidence/100,000 Population

Polycythemia Vera

2.81

Essential Thrombocythemia

1.51

Primary Myelofibrosis

0.41

Multiple Myeloma

5.52

Chronic Myeloid Leukemia

1.62

The state of research

For many years, medical research into the cause and treatments of MPNs had been limited. The last full scale medical research study, the Polycythemia Study Group (PVSG) was completed 4 decades ago. Since then, the COMFORT I and COMFORT II studies brought the first commerically approved drug for certain MPNs, Jakafi.  There remains a great need for more therapeutic options for MPNs.

At present treatments for MPN are generally used to control disease symptoms. Depending on the type of MPN and the symptoms experienced by patients, different medications may be used. Some therapies, such as hydroxyurea, anagrelide or interferon-alpha, reduce the number of abnormal cells. Aspirin is usually beneficial in ET and PV patients.

Phlebotomy is a mandatory measure in PV patients with high red blood cell count. Patients with a low red cell count may receive a blood transfusion. Those with low platelets may benefit from platelet transfusion. Growth factors that stimulate growth of bone marrow cells, given as injection under the skin, may benefit patients with low blood cell count. Other medications, such as thalidomide, steroids and other hormones, cladribine and busulfan may help treat some MPN. Radiation therapy or surgical removal of the spleen may also be useful in certain circumstances. For some patients, a Bone Marrow or a Stem Cells transplant may be an option.

In the last few years it is clear that the world of MPN research has started to attract a great deal more attention. Then the recent discovery of the JAK2 V617F mutation gene has ignited a great deal of new and exciting scientific discourse on the genetic causes of the MPNs and much speculation on the possibility of finding new genetically targeted drugs and therapies. JAK2 V617F is found in over 90% Polycythemia patients and approximately 50% of Myelofibrosis and Essential Thrombocythia patients.

Based on this findings the NIH awarded a multi-million grant to the MPN-RC Consortium which will focus on understanding the genetic underpinnings of these diseases, the effectiveness of existing therapies, and the acceleration of basic research. The formation of the MPN-RC marks a major initiative to accelerate the development of new drugs for MPNs. Patient involvement at all stages of the process keeps our focus on the extension of life expectancy and the improvement of patient quality of life.

In spite of the growing recognition that intensified research into these diseases is both necessary and appropriate, there are still significant barriers which limit the potential effectiveness of this research.


Polycythemia Vera

Polycythemia vera is one of the myeloproliferative neoplasms (MPN). In this variant, there is uncontrolled production of mature red cells leading to high hematocrit (Hct), hemoglobin (Hg) and red cell mass with increased blood volume and viscosity which can lead to complications involving clotting or bleeding episodes if not controlled.

PV is fairly rare, occuring in approximately 1 in 100,000 and tends to be slightly more common among men and people of Jewish ancestry. Between its rarity and the fact that many patients live a long time PV it hasn’t been studied the way “major” diseases have and there is no consensus among the experts about who, what, why, and how to treat.

Diagnosis

Polycythaemia vera is diagnosed using a number of tests including:

  • Physical examination
  • Medical history
  • Blood tests, including complete blood count (CBC)
  • Vitamin B12 blood test
  • Bone marrow biopsy

Onset and Symptoms

Typically the onset of disease is sometime after the age of 50 years with a slow but persistent progression.

The red blood cells the white blood cells and the platelets are all created from stem cells within the bone marrow and their numbers and ratio are carefully regulated to ensure that proper balance is maintained. In a person with Polycythaemia Vera the stem cells are abnormal and produce more blood cells than is necessary. Most often, the bone marrow makes too many red blood cells. The reasons for this are unknown. Many of the extra blood cells are also abnormal. Since polycythaemia vera is more common among people with Jewish ancestry, a genetic link could be involved.

The symptoms of polycythaemia vera include:

  • Headache
  • Dizzy spells
  • Itching skin, especially after bathing
  • Flushing of the skin, especially the face
  • Breathlessness
  • Phlebitis (inflammation of the vein)
  • Vision problems
  • Skin rashes
  • Blue tinge to the skin (cyanosis)
  • Fatigue
  • Gout
  • Kidney stones
  • Enlarged spleen (splenomegaly)

Progression of the disease in the BM and complications

Over time, the furiously hard-working bone marrow may stop working altogether and the stem cells are replaced by non-functioning scar tissue. This condition is known as myelofibrosis. On the other hand, around one in 10 people with polycythemia vera develop acute myeloid leukemia, which is the most common type of leukemia affecting adults (particularly older people). Some of the other complications of polycythaemia vera include:

  • Thrombosisthe most common cause of death in people with polycythemia vera.
  • Stroke
  • Heart attack
  • Peptic ulcer
  • Gastric bleeding
  • Heart failure

Treatments

Without treatment, around half of all people with symptomatic polycythemia vera will die in less than two years. There is currently no cure, but treatment can extend the person’s life span by thinning the blood and reducing the risk of blood clots and other complications. Options include:

  • Weekly removal of one unit of blood, until red blood cells make up less than 45 per cent of the overall blood volume. This procedure is called either a phlebotomy or venesection.
  • Drug therapy to suppress the activity of the bone marrow, such as frequent injections of interferon or tablets called hydroxyurea.
  • Drugs to reduce the risk of blood clots, such as aspirin or Warfarin

Things to remember

  • Polycythemia vera is a type of blood disorder characterized by the production of too many blood cells, typically red blood cells.
  • It is caused by abnormal functioning of the bone marrow, but the reason for this remains unknown.
  • Polycythemia vera is a rare condition that tends to be slightly more common among men and people of Jewish ancestry.
  • There is currently no cure.
  • Treatment options include drug therapy and the regular removal of blood units.


Essential Thrombocythemia

Essential thrombocythemia (ET) is one of four rare, myeloproliferative neoplasms (MPNs) and it is characterized by overproduction of the precursor cells to blood platelets megakaryocytes.

A platelet is a very small blood cell. Its function is to start the process of blood clotting in response to blood vessel injury. Another word for platelet is thrombocyte. The term thrombocythemia means an excess of platelets in the blood. The terms essential or primary indicate that the increase in platelets is not the result of another condition, such as arthritis or iron deficiency anemia.

In essential thrombocythemia changes to the stem cell’s DNA leads to the overproduction of megakaryocytes in the marrow. Each of these giant cells breaks up into small pieces and by this process produces hundreds-to-thousands of platelets. When present in very large numbers, these platelets may not function normally and can cause a blockage in blood vessels, known as a thrombus. Less often, the very large number of platelets can also cause bleeding problems.

Essential thrombocythemia is an uncommon disease. Between 0.1 and 2.4 new cases per 100,000 people are estimated to occur each year. The number of individuals living with essential thrombocythemia is relatively high because this disease does not generally shorten life expectancy.

Essential thrombocythemia occasionally occurs in older children, but is most commonly diagnosed in adult men and women. Formerly, it was generally considered to be a disease of adults age 50 and above. However, today platelet counts are often part of blood tests that accompany health examinations. As a result, younger individuals are being diagnosed with more frequency than in the past.

As many as two-thirds of patients are without symptoms (asymptomatic) upon initial examination. Most patients present with symptoms related to small or large vessel thrombosis or minor bleeding. Presentation with a major bleeding episode is very unusual. Clots may occur in the small arteries of the toes and fingers, leading to pain, warmth, tissue death (gangrene) and/or classic erythromelalgia. Erythromelalgia refers to a syndrome of redness and burning pain in the extremities. The incidence of the thrombotic (blood clotting) and bleeding episodes is minimized, but not eliminated, with reduction of the platelet count to normal.

In some instances, this chronic disorder may be progressive, evolving in relatively rare cases into acute leukaemia or myelofibrosis.

The term secondary thrombocythemia is used to describe the problems involving persistent, high blood platelet counts associated with some underlying condition such as malignancy, infection, inflammatory disease, or iron deficiency.

Diagnosis

Essential thrombocythemia is often identified in symptom-free patients when a blood test (done as part of a periodic health examination) shows a higher than normal platelet count. Or, a physician may order blood tests for a patient who has a blood clot, unexpected bleeding, or a mildly enlarged spleen.

The platelet count is a medical blood test. The normal values range from about 175,000 to 350,000 platelets per microliter of blood in most laboratories. Essential thrombocythemia is a consideration if the platelet count is above 600,000/ml of blood and remains high over a period of observation and there is no other evident cause for an elevated platelet count.

There are no specific tests that can be used to establish the diagnosis of essential thrombocythemia with certainty. Confirmation of the diagnosis requires further examination and testing to rule out other conditions as the cause of the high platelet count. Several conditions can result in an increase in platelets, including:

  • Inflammatory disorders, such as arthritis
  • Iron deficiency anemia
  • Certain types of cancer
  • Splenectomy

Generally, a physician will consider these conditions first to determine if there is an explanation for the increase in platelets. In most cases, the diagnosis of essential thrombocythemia is made based on

  • A high platelet count that persists over time
  • A slightly lower than normal blood hemoglobin concentration (mild anemia) and a slightly higher than normal white cell count
  • An examination of the marrow that is compatible with the diagnosis (abnormal and higher than normal number of megakaryocytes)
  • The absence of evidence for other clonal blood diseases that can be accompanied by increased platelets, such as chronic myelogenous leukemia and idiopathic myelofibrosis

Symptoms and complications of essential thrombocythemia

Many patients with essential thrombocythemia do not have any signs or symptoms. Other patients may have:

  • redness of the skin
  • burning, or throbbing pain in their feet and hands
  • headache
  • dizziness
  • weight loss
  • itching
  • a mildly enlarged spleen
  • unexpected or exaggerated bleeding (Abnormal bleeding is infrequent and usually occurs only in the presence of a very high platelet count.)
  • thrombosis (abnormal clotting of the blood)

Thrombosis is a more common complication of essential thrombocythemia than is bleeding. A blood clot can occur in either an artery or less frequently, in a vein. This complication can be very serious if the clot blocks blood flow to an organ, such as the brain (causing a stroke) or heart (causing a heart attack). Older patients with underlying vascular disease and very high platelet counts (1,000,000 per microliter and above) may be at highest risk for a thrombosis, but there is no certain way to gauge risk. Clotting complications may occur in patients with only a slightly elevated platelet count.

Treatment

Treatment decisions should be guided by the risk of clotting or bleeding complications in a patient. For some patients with no signs of the disease other than an increased platelet count, the risk of complications may be low. Observation may be the approach used by the physician for such patients, especially in the case of a younger person with no other cardiovascular risk factors, such as high cholesterol, diabetes, smoking, obesity or hypertension.

Physicians may use chemotherapy to reduce high platelet count in patients with previous bleeding or clotting episodes or those who are at high risk for such complications.

Risks for clotting complications include:

  • A history of previous clot
  • Cardiovascular risk factors
  • Advanced age, although studies are not definitive about this factor

Risk factors for bleeding include:

  • A platelet count of 2,000,000 per microliter and above
  • Aspirin or other non steroidal inflammatory (NSAID) drug use

The most commonly used drugs to treat essential thrombocythemia are hydroxyurea (Hydrea®), anagrelide, and interferon alpha.

Hydroxyurea is myelosuppressive agent that is can be used as initial therapy for essential thrombocythemia. Hydroxyurea often is successful in decreasing platelet count within several weeks, with few short-term side effects. However, there is some evidence that hydroxyurea is associated with an increased risk for developing acute leukaemia after long-term therapy. Hydroxyurea is generally not used for treating younger patients and patients without symptoms.

Anagrelide is a non-cytotoxic drug that effectively decreases platelet formation in most patients. It has not been associated with leukemia development and it is a first-line therapy alternative to other treatments, such as hydroxyurea. Side effects to anagrelide can occur, including fluid retention, heart and blood pressure problems, headaches, dizziness, nausea, and diarrhea. Older patients and patients with heart disease are generally not treated with anagrelide.

Interferon-alpha is another effective treatment for lowering platelet counts in patients with essential thrombocythemia. However, there are certain considerations that limit its usefulness:

  • Interferon alpha is given by injection and is costly
  • Some patients develop moderately severe flu-like symptoms
  • Some patients get confused or depressed
  • Other complications may develop

Aspirin may be effective for patients with recurring clotting complications. However, it may also increase the risk of bleeding. For these reasons, the role of aspirin in treating essential thrombocythemia is controversial at present.

Plateletpheresis is a process that uses a device to skim platelets from a patient’s blood and then return the plasma (liquid portion of blood) and red cells back to the patient. It is only used in emergency situations, such as acute clotting complications, when the platelet count is very high and needs to be reduced quickly. The platelet reducing-effect of this therapy is temporary and may trigger an increase to an even higher platelet count.

Prognosis and course of essential thrombocythemia?

Long-term follow-up of essential thrombocythemia patients indicates that lifespan is not usually affected by the disease. However, if thrombosis occurs and a vital organ, such as the brain or the heart is affected, patients may have disability. Among untreated pregnant patients with essential thrombocythemia, there is a risk to the fetus.

In occasional cases, essential thrombocythemia can transform to another myeloproliferative neoplasm.

Patient Support Groups

Web Links

In the fight against blood cancer, research and support can make all the difference while we fight to find better treatments and a cure. While we are waiting you need a partner to get you through. MPN Research Foundation is there for you, not only funding research that is moving the science forward, but also connecting you to information and other people who are going through this same experience.

Cancer Support Community (CSC) is dedicated to ensuring that all people impacted by cancer are empowered by knowledge, strengthened by action, and sustained by community. This global network of 175 locations, including CSC and Gilda’s Club centers, health-care partnerships, and satellite locations that deliver more than $50 million in free support services to patients and families. Resources about MPNs are now available in Arabic, Chinese, Korean, Russian, Spanish and Vietnamese! If you or a loved one has been diagnoses with an MPN, but English is not your primary language, the Cancer Support Community is here to help.

Patient-run support group for daily emailed information, research and questions and answers from nearly nearly 3,000 members, plus archives dating back to 1996. To sign-up please follow the instructions here: http://listserv.acor.org/scripts/wa-ACOR.exe?SUBED1=MPN-NET&A=1 or peruse the website.

MPN Advocacy and Education International is dedicated to providing the knowledge, support, and resources patients will need as they adjust to living with an MPN through educational symposia in several cities each year, website access, free webcasts of each program, collateral materials, and direction to people, resources and other organizations that can help.

At the Canadian MPN Research Foundation, we’re committed to standing with you in the fight against polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) – the group of blood cancers collectively known as myeloproliferative neoplasms.

Come join us! We are an International email MPD/MPN Support group for those with Essential Thrombocythemia, Polycythemia Vera, and Myelofibrosis. We remember exactly what it was like to have more questions than answers! Here, you’ll meet people that have ‘been there and done that’ with hearts that under- stand when it seems no one else does.

Beyond publications, the MPNforum supports the MPNclinic, maintains a List of Patient Recommended Hematologists, and advocates for research and support projects on behalf of the MPN community. The magazine and an extensive catalog of articles is available free, without subscription, at www.mpnforum.com. The MPN Quarterly Journal, devoted to in-depth scientific discussions and reviews, is at www.mpnjournal.org.

MPN Voice’s is to provide clear and accurate information and emotional support to everyone who suffers from a myeloproliferative disorder. We’ve also recently begun funding research towards better treatments – and we hope one day a cure. MPD Voice received a UK-wide award for innovative service to MPD patients in 2009.

Myeloproliferative Disease Support Group and Mailing List – Information on chronic myelogenous leukemia, polycythemia vera, essential thrombocytemia, agnogenic myeloid metaplasia, myelodysplasia, mylelofibrosis. For patients and health professionals.

SIGNUP and MPD SUPPORT ARCHIVES: http://www.mpdsupport.org/

Patient Power® is devoted to helping you, the cancer patient or survivor and your family through knowledge, to get the best medicine and return to or maintain good health.

Founded in 2011, MPNforum 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.  With 12,000+ monthly readers, MPNforum is the most widely followed independent international on-line monthly magazine focused on myeloproliferative neoplasm patients and caregivers.

MPN Cancer Connection (MPN-CC) provides support services, resources and referrals to help MPN patients manage the on-going emotional and financial challenges of living with a chronic cancer.

To provide a directory of resources for people living with MPNs (Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis)

  • Curated by MPN patients and advocates
  • Provides links to reputable MPN-related resources, such as for support services, financial assistance, clinical trials, transplant information,etc.
  • Offers MPN-NET, an online support group, as well as face to face support groups
  • Offers conferences, newsletters and online videos
  • Provides referrals to specialists and links to medical literature.

Everything we do is focused on improving the lives of everyone affected by blood cancer, the fifth most common cancer in the UK. We want to bring forward the day when every single person affected by blood cancer is able to live a full life. We provide everyone affected by blood cancer with information they can trust, in language they can understand. Through our information and support services, we empower and connect people affected by blood cancer so that they can live their life to the full.

Myeloproliferative Disorders Australia (MPD-Oz) website has been established to provide information about Myeloproliferative Disorders and to promote and share Australian specific resources and to provide support to people with Myeloproliferative Disorders and their families.

The MEJ Thrombocythaemia discussion forum is the only message board purely dedicated to Thrombocythemia. Topics are archived into yearly folders, and are closed off at the end of the year. This allows archived topics to be viewed, but not responded to within the archive.