This frequently asked question (FAQ) section has been developed to help you finding some answers to questions you may have concerning your disease.
We gratefully acknowledge some related websites, from which we borrowed and slightly modified FAQs: http://www.mpdinfo.org/faq/faq_cml.html
These FAQs and the ones added by our own MPN-RC members, have all been reviewed by our specialists for correctness and topicality.
Statements contained herein are of a general nature and should not be interpreted as personal advice in stead of recommendations by your physician or other relevant professional consultant.
What is Myeloproliferative Disease (MPD)?
Myeloproliferative diseases (MPDs) are a heterogenous group of disorders characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. MPDs consist of 4 diseases: chronic myelogenous leukemia (CML); polycythemia vera (PV); essential thrombocythemia (ET); Idiopatic Myelofibrosis (IM). MPD may evolve into one of the other myeloproliferative conditions, transform to acute leukemia, or both.
Some evidence indicates that MPDs arise from malignant transformation of a single stem cell. In MPD, one abnormal cell clone that produces several types of blood cells, a so called pluripotential hematopoeitic precursor cells (PHPC) 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. But what we do have in the myeloproliferative disorders is abnormal over or under production of a particular cell type. Thus MPD involves the improper balance between production of different blood cell types just as much as it involves abnormality of any given blood cell type.
Is this cancer?
What is myelofibrosis?
It is a disease of the bone marrow in which the bone marrow becomes fibrotic. This fibrotic scar tissue inside the marrow cavity eventually takes over leading to increasingly inefficient blood cell production and ultimately may result in bone marrow failure. It may be called by several names including primary or idiopathic myelofibrosis (more common in the British health system) or agnogenic myeloid metaplasia (usually used in the USA). These names describe a situation where myelofibrosis is the first disease diagnosed. It is also possible to have myelofibrosis as a consequence of another myeloproliferative diseases such as polycythemia vera (PV), essential thrombocythemia (ET), or chronic myelogenous leukemia.
In the setting of a myeloproliferative disorder, myelofibrosis is accompanied by varying degrees of myeloid metaplasia (often seen as enlargement of spleen and/or liver), due to reactivation of fetal hematopoietic sites than are normally dormant in adult life. It is this combination that distinguishes myeloproliferative disease-related myelofibrosis from the secondary or interactive myelofibrosis that occurs in the setting of malignancy, chemical or physical injury, infection or infarction. The increase of fibrous tissue in the bone marrow, the extramedullary haematopoeisis that presents itself primarily as progressive enlargement of the spleen (splenomegaly), and the leuko-erythroblastosis in the peripheral blood form the basis of the myriad clinical presentations of myelofibrosis. Clinical and laboratory findings, the course and complications and the ultimate outcome are determined by the degree of preservation of normal haematopoeitic tissue, the extent of hematic dysplasia, and the balance between cell proliferation and cell destruction.
How is myelofibrosis diagnosed?
Usually by a physician noticing low red cell counts and perhaps other abnormal blood counts such as elevated white cell and/or platelet count during a routine exam or as a result of an examination to determine the cause of a patient’s complaints of feeling more tired than usual or that their abdomen is tender and enlarged or bloated (this comes from the enlarged spleen), bruising, etc. An alert doctor will request a full blood screen which will identify that some elements of the blood counts are abnormal and may follow up with an abdominal ultrasound or other scan before sending a patient to a haematologist for further work-up. To be sure of the diagnosis a bone marrow biopsy is required to test the state of the marrow itself and provide conclusive evidence of the disorder.
What is the value of the bone marrow biopsy and how do I cope with it?
It is important as it provides a bench mark for measuring the progress of the bone marrow directly. The blood reports show the consequences of the state of the bone marrow. Nothing beats firsthand information. Some doctors claim they can tell by peripheral blood counts and do not rely on bone marrow biopsies. As you can see from the above criteria, it is virtually impossible to stage the disease without this tool. And staging provides a guide to the most appropriate treatment option.
However the procedure may be difficult as local anesthetics cannot reach the bone marrow itself. You may find that if you prepare with a relaxant (mild tranquilizer) about an hour ahead that the procedure (which takes 3 – 30 minutes depending on skill and bone density) can be coped with.
What is the prognosis of myelofibrosis?
In general, the survival of patients with idiopathic myelofibrosis seems to a large extent programmed by their presenting findings and is not very much altered by therapy. Approximately 60% of patients with idiopathic myelofibrosis live 5 years. There is a significant cohort of patients who live 10 years or more. Patients with idiopathic myelofibrosis who tend to do very well include those whose presenting hemoglobin levels are greater than 10 gm/dl, platelet counts greater than 100×3/ul and only modest enlargement of the liver. Spleen size and sex seem to have no prognostic significance.
How could I have got myelofibrosis?
If you were previously diagnosed with a myeloproliferative disorder (MPD) such as essential thrombocythemia, polycythemia vera or chronic myelogenous leukemia, your myelofibrosis is reactive and secondary to the pre-existing MPD. If it arose de novo with no prior history of another MPD, no one knows for sure. You might have had a prior undiagnosed myeloproliferative disorder, discovered only after you developed myelofibrosis. It might be likely to be a specific gene abnormality which develops over a period of years.
What are the main treatment options for myelofibrosis?
For asymptomatic patients, no treatment is necessary.
The profound anemia that develops in this disease usually requires red blood cell transfusion. Red blood cell survival is markedly decreased in some patients; this can sometimes be treated with glucocorticoids. Disease-associated anemia may occasionally respond to erythropoietin, hydroxyurea, cladribine, thalidomide, or interferon.
Hydroxyurea is useful in patients with this disease but may have a potential leukemogenic effect (initiation or pregression of leukemic disease). In patients with thrombocytosis and abnormal enlargement of the liver after surgical removal of the spleen, cladribine has shown responses as an alternative to hydroxyurea. The use of interferon alfa can result in hematologic responses, including reduction in spleen size in 30% to 50% of patients, though many patients do not tolerate this medication. Favorable responses to thalidomide have been reported in about 20% to 60% of patients. Another approach involves allogeneic peripheral stem cell, umbilical stem cell or bone marrow transplantation when a suitable sibling donor is available.
Painful abnormal enlargement of the spleen can be treated temporarily with chemotherapy (hydroxyurea), interferon, or radiation therapy, but often requires the surgical removing of the spleen (splenectomy).
The decision to perform splenectomy represents a weighing of the benefits (i.e., reduction of symptoms, decreased portal hypertension, and less need for red blood cell transfusions) versus the debits (i.e., risk of postoperative deaths of 10% and illness of 30% caused by infection, bleeding, or thrombosis).
Making treatment decisions in myelofibrosis.
Why is a particular treatment recommended? How important are social and psychological factors in choosing a treatment option? As you can see from the above discussion, there isn’t a single myelofibrosis with a given set of symptoms and conditions which respond to a specific treatment. If a patient’s marrow is still overproducing platelets, red cells and white cells, their treatment needs are completely different from a patient whose marrow is barely functioning.
Each patient needs to work with his or her doctor in deciding on the best treatment option. Only your doctor has reviewed your records and test results and can recommend a specific course of action that has the best chance of dealing with your condition. The important thing from the patient standpoint is to understand what treatment options are available and discuss what is best for you with your hematologist.
Coming to the understanding that these are chronic, incurable (without a successful bone marrow/stem cell transplant) conditions that require medical monitoring and treatment for the remainder of one’s life can be difficult and we all cope in different ways. Some patients feel that quality of life issues are the most important consideration. There are several women in our group who were quite upset by hair loss, fatigue and lack of response in shrinking their spleen and opted for splenectomy so they could stop the interferon. Some do not have insurance that covers the cost of a particularly treatment. In countries with a national health care system, for example, interferon may not be available as a treatment option unless the patient pays for it personally. In the United States, Medicare patients face difficult economic issues if interferon is the drug of choice.
Living with a potentially life-threatening chronic disease is difficult. You will need to learn how to chill out so to speak. This is not like a broken leg or similar physical injury. It is a chronic disease which will require you to make certain changes in your life from now on; for ever more. Unless you have a successful bone marrow/stem cell transplant; which is not considered standard care at the moment; you will live with this for the rest of your life. And your life will be different.
If I choose one treatment for myelofibrosis, does this influence any later choice, e.g. bone marrow transplant?
It is not known for sure but it seems highly possible that the choice you make about treatment may influence your system’s capacity to deal with subsequent choices. Prolonged chemotherapy damages organs and patients may be less able to weather the severe or reduced intensity conditioning (RIC) chemotherapy required prior to a bone marrow transplant.
However, since some do well for a period of years with no treatment and some have seen improvement or reversal on interferon, this presents difficult choices if one is young enough for a transplant and has a matched related donor.
Are there any new treatment options coming along?
There is a huge amount of material available on the Internet about treatments and case reports. But as myeloproliferate diseases are rare, there is not much research specifically focussing at these diseases. For this reason an international research Consortium named the MPD-RC has been created. The MPD-RC is an international, multi-institutional no profit consortium set up to coordinate, facilitate, and perform basic and clinical research investigating the genetic and cellular mechanisms of the Philadelphia Chromosome (Ph) negative myeloproliferative disorders (MPD). The ultimate goal is to develop novel therapeutic strategies to improve the management of patients with this type of diseases. This program is led by Dr. Ronald Hoffman, a nationally and internationally recognized investigator who has brought together highly qualified and experienced investigators, and efficiently established a complex, well assembled, highly synergistic and innovative structure.
How often do I need check-ups?
Different doctors will have different expectations – but you should expect monthly checks in the early stages while the doctor or team determines whether you are in a stable or deteriorating state; followed by two or three monthly checks if you are early and stable.
What is my life expectancy?
The only answer is that no one knows for sure. It may be as little as three years (less with the acute form) but it may be 10 – 15 years – or who knows it may be the full span if you have a successful bone marrow/stem cell transplant.
What impact may myelofibrosis and its treatment have on my fertility/menopause?
This is an issue you need to discuss with your doctor. But if you have a bone marrow/stem cell transplant, you can expect instant menopause.
What impact may there be on sexuality?
When one is faced with a diagnosis of a life threatening disease this has a real impact on both the individual and the relationship they are in. Our sense of ourselves as a whole healthy person is challenged and we are forced to face mortality. Over time our body does not work as well as before and we may become very focused on the disease as it assumes a greater portion of our lives. The increased anxiety as well as effects of medication all impact on one’s sexuality.
The reality is that things are not going to be what they were before. The challenge is to find positive ways to maintain and enhance the physical and emotional benefits that accrue from the expression of our sexuality.
What are bone marrow transplantation and peripheral blood stem cell transplantation?
Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants:
In autologous transplants, patients receive their own stem cells.
In syngeneic transplants, patients receive stem cells from their identical twin.
In allogeneic transplants, patients receive stem cells from their brother, sister, or parent. A person who is not related to the patient (an unrelated donor) also may be used.
How are peripheral blood stem cells obtained for transplantation?
The stem cells used in PBSCT come from the bloodstream. A process called apheresis or leukapheresis is used to obtain PBSCs for transplantation. For 4 or 5 days before apheresis, the donor may be given a medication to increase the number of stem cells released into the bloodstream. In apheresis, blood is removed through a large vein in the arm or a central venous catheter (a flexible tube that is placed in a large vein in the neck, chest, or groin area). The blood goes through a machine that removes the stem cells. The blood is then returned to the donor and the collected cells are stored. Apheresis typically takes 4 to 6 hours. The stem cells are then frozen until they are given to the recipient.
How are umbilical cord stem cells obtained for transplantation?
Stem cells also may be retrieved from umbilical cord blood. For this to occur, the mother must contact a cord blood bank before the baby’s birth. The cord blood bank may request that she complete a questionnaire and give a small blood sample.
Cord blood banks may be public or commercial. Public cord blood banks accept donations of cord blood and may provide the donated stem cells to another matched individual in their network. In contrast, commercial cord blood banks will store the cord blood for the family, in case it is needed later for the child or another family member.
After the baby is born and the umbilical cord has been cut, blood is retrieved from the umbilical cord and placenta. This process poses minimal health risk to the mother or the child. If the mother agrees, the umbilical cord blood is processed and frozen for storage by the cord blood bank. Only a small amount of blood can be retrieved from the umbilical cord and placenta, so the collected stem cells are typically used for children or small adults.
Are any risks associated with donating bone marrow?
Because only a small amount of bone marrow is removed, donating usually does not pose any significant problems for the donor. The most serious risk associated with donating bone marrow involves the use of anesthesia during the procedure.
The area where the bone marrow was taken out may feel stiff or sore for a few days, and the donor may feel tired. Within a few weeks, the donor’s body replaces the donated marrow; however, the time required for a donor to recover varies. Some people are back to their usual routine within 2 or 3 days, while others may take up to 3 to 4 weeks to fully recover their strength.
Are any risks associated with donating peripheral blood stem cells?
Apheresis usually causes minimal discomfort. During apheresis, the person may feel lightheadedness, chills, numbness around the lips, and cramping in the hands. Unlike bone marrow donation, PBSC donation does not require anesthesia. The medication that is given to stimulate the release of stem cells from the marrow into the bloodstream may cause bone and muscle aches, headaches, fatigue, nausea, vomiting, and/or difficulty sleeping. These side effects generally stop within 2 to 3 days of the last dose of the medication.
How does the patient receive the stem cells during the transplant?
After being treated with high-dose or reduced intensity conditioning chemotherapy and/or radiation, the patient receives the stem cells through an intravenous line just like a blood transfusion. This part of the transplant takes 1 to 5 hours.
Are any special measures taken when the cancer patient is also the donor (autologous transplant)?
The stem cells used for autologous transplantation must be relatively free of cancer cells. The harvested cells can sometimes be treated before transplantation in a process known as “purging” to get rid of cancer cells. This process can remove some cancer cells from the harvested cells and minimize the chance that cancer will come back. Because purging may damage some healthy stem cells, more cells are obtained from the patient before the transplant so that enough healthy stem cells will remain after purging.
What happens after the stem cells have been transplanted to the patient?
After entering the bloodstream, the stem cells travel to the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets in a process known as “engraftment.” Engraftment usually occurs within about 2 to 4 weeks after transplantation. Doctors monitor it by checking blood counts on a frequent basis. Complete recovery of immune function takes much longer, however—up to several months for autologous transplant recipients and 1 to 2 years for patients receiving allogeneic or syngeneic transplants. Doctors evaluate the results of various blood tests to confirm that new blood cells are being produced and that the cancer has not returned. Bone marrow aspiration (the removal of a small sample of bone marrow through a needle for examination under a microscope) can also help doctors determine how well the new marrow is working.
What are the possible side effects of BMT and PBSCT?
The major risk of both treatments is an increased susceptibility to infection and bleeding as a result of the high-dose chemotherapy treatment. Doctors may give the patient antibiotics to prevent or treat infection. They may also give the patient transfusions of platelets to prevent bleeding and red blood cells to treat anemia. Patients who undergo BMT and PBSCT may experience short-term side effects such as nausea, vomiting, fatigue, loss of appetite, mouth sores, hair loss, and skin reactions.
Potential long-term risks include complications of the pretransplant chemotherapy and radiation therapy, such as infertility (the inability to produce children); cataracts (clouding of the lens of the eye, which causes loss of vision); secondary (new) cancers; and damage to the liver, kidneys, lungs, and/or heart.
With allogeneic transplants, a complication known as graft-versus-host disease (GVHD) sometimes develops. GVHD occurs when white blood cells from the donor (the graft) identify cells in the patient’s body (the host) as foreign and attack them. The most commonly damaged organs are the skin, liver, and intestines. This complication can develop within a few weeks of the transplant (acute GVHD) or much later (chronic GVHD). To prevent this complication, the patient may receive medications that suppress the immune system. Additionally, the donated stem cells can be treated to remove the white blood cells that cause GVHD in a process called “T-cell depletion.” If GVHD develops, it can be very serious and is treated with steroids or other immunosuppressive agents. GVHD can be difficult to treat, but some studies suggest that patients with leukemia who develop GVHD are less likely to have the cancer come back. Clinical trials are being conducted to find ways to prevent and treat GVHD.
The likelihood and severity of complications are specific to the patient’s treatment and should be discussed with the patient’s doctor.
What is polycythemia vera?
In this variant, the PHPC clone (stem cell responsible for the production of various blood cell types) produces too many red blood cells which literally causes the patient to have “too much blood”. The resulting increased blood volume and thickness leads to the complications associated with this disease. The risks of complications can be reduced by appropriate treatment.
Who can get polycythemia vera?
Polycythemia vera is primarily a disease of middle-aged or elderly patients but we are seeing young patients as well. In a retrospective study of 1231 PV patients followed for 20 years, the largest cluster of PV patients were found in the 41 to 80 age groups with the highest numbers in the 51-75 age groups. (The ages ranged from under 10 to over 90). SourcePolycythemia Vera: The Natural History of 1213 Patients Followed for 20 years, Gruppo Italiano Studio Polycythemia, Annals of Internal Medicine, Volume 123, Number 9, 1 November 1995.
What are the symptoms and risks of polycythemia vera?
Polycythemia vera is insidious in onset and may be present for 1 to 2 years before medical attention is sought. During the asymptomatic phase, polycythemia vera may be discovered at the time of a routine examination which reveals an elevated hematocrit. Polycythemia vera is the only myeloproliferative disease in which involvement of the erythrocytes (red cells) results in an increased red cell mass. This feature of “too much blood” results in unique symptoms and complications. Basically, patients are at higher risk of clotting or bleeding problems related to the resulting hypervolemia (increased blood volume) and viscosity (thickness). Thrombosis and haemorrhaging are big problems at the outset, especially before diagnosis but once this is properly controlled, risks are reduced.
Symptoms caused by the elevated hematocrit are present initially in 30 to 50% of patients and may cause the patient to seek medical attention for symptoms such as plethora (too much blood), headache, dizziness, visual disturbances, inability to concentrate and parethesis (numbness). Related findings at diagnosis can include hypertension, a high cardiac output state and evidence of vascular status. Significant arterial or venous thrombosis occurs in one third to one half of uncontrolled cases, and these events may precede the diagnosis (heart attack, stroke, pulmonary embolism, clots in the veins leading to liver, etc).
How is polycythemia vera diagnosed?
While we have heard of cases where a diagnosis is made simply based on blood counts, most hematologists follow the guidelines of the Polycythemia Vera Study Group and run certain diagnostic tests. If the Study Group criteria are met, then a diagnosis can be made with certainty.
The criteria that must be met for a diagnosis of polycythemia vera at diagnosis are a demonstration of increased red cell mass combined with an enlarged spleen (splenomegaly) which is presenting 75% of cases or any two other features of pluripotential precursor cell involvement, such as increased platelet counts (35-50%), neutrophilia (50-80%), increased leukocyte alkaline phosphate activity (80%), or increased vitamin B12 binding protein (67%).
There are certain features in the bone marrow as well. The bone marrow uniformly shows panmyelosis (increase of all the bone marrow elements) with erythroid hyperplasia (excessive proliferation of red cells) and increased megakarocyte (platelet precursor) proliferation. Increased reticulin is present in 20% of patients but fibrosis is usually absent. Cultured bone marrow produces erythroid colonies, and there is a marked increase in the number of erythroid colonies formed with the addition of erythropoeitin (increased erythropoeitin sensitivity).
What causes complications of polycythemia vera?
As mentioned above, the increased blood volume and increased circulating red cell mass play a key role in the symptoms and complications experienced in cases of uncontrolled polycythemia vera. Thrombosis and hemorrhage are the major complications. Thrombosis may be arterial (coronary, cerebral, peripheral vascular) or venous (involving peripheral, hepatic or portal veins). Small vessel insufficiency produces cyanosis (slightly bluish, grayish or dark purple discoloration), erythromyelagia (pain in fingers and toes), or even gangrene (mortification) of the digits. Mild hemorrhagic phenomena such as nosebleeds (epistaxis), bleeding gums and easy bruisability are common. More severe bleeding problems such as melena (black tarry stool), hemostatsis (stagnation of blood-lack of circulation), menorrhagia (excessive menstrual bleeding) or hemoptysis (coughing up blood which can originate from the mouth, larynx, trachea, bronchi or lungs) occurs in 10% of patients. However, there is good news. With modern treatment, many PV patients are enjoying a normal life expectancy.
How do I reduce the risk of complications of polycythemia vera?
Restoration of a normal blood volume and hematocrit markedly reduces the incidence of complications in polycythemia vera. Management based on this insight into the causes of the complications and symptoms of polycythemia vera has resulted in a significant improvement in survival. Treatment of erythemia is targeted at reduction of the hematocrit to normal levels at which optimum cerebral blood flow is achieved. Views on what this level should be varies and one should always discuss this with your own doctor. Some experts feel that the hematocrit should be maintained below 42 in women and below 45 in men. According to a recent article, some also feel that platelet counts should be maintained below 400,000. Treatment options also vary depending upon the particular circumstances of each patient.
What else might I experience with polycythemia vera?
There are a number of other metabolic abnormalities which occur in MPD patients, including patients with PV. Briefly, MPD patients, including PV patients may exhibit high uric acid levels (hyperuricemia, 50%) which can lead to joint pain and gout, low cholesterol levels (hypocholesterolemia), high histamine levels (hyperhistaminea) and histaminuria occur in two thirds of MPD patients which can produce itching, heart burn, acid eructation, peptic ulcer, small bowel hyper motility, flushing and angioneurotic edema. Hypermetabolism is commonly manifested as weakness and fatigue that occur in MPD patients not experiencing anemia.
How is polycythemia vera treated?
Phlebotomy has been one of the most common initial therapies for many polycythemic patients. There has been a lot of experience with it. The purpose of phlebotomy is to reduce the red blood cell mass (RBC mass)-that is, the total number of circulating red blood cells, and to do it fairly quickly, at least in the beginning when the hematocrit (Hct) is high.
Phlebotomy is a rapid way of reducing the increased red blood cells down to normal levels. When red cells are removed by phlebotomy about 400-450cc (one pint of blood) is removed, of which approximately 60 percent are red blood cells (about 300 cc). The body only makes about 17 cc (½ oz) of red blood cells a day, so in a normal individual it would take about one month to make up for one phlebotomy under normal conditions. The rate at which polycythemia vera patients regenerate can vary.
Since red blood cells are made so slowly, rapid changes in the blood volume (RBC plus plasma) are accomplished by changes in the plasma which are controlled by the kidney, as plasma is mostly water. The blood volume is adjusted by the body to maintain an adequate blood pressure. When the blood volume falls quickly, as in bleeding, the body gets a signal to increase the amount of fluid that is circulating. That is why an early sign of blood loss is thirst.
After phlebotomy, as the blood increases its plasma content, the hematocrit falls, so the red blood cells are now diluted. The benefit of reducing the hematocrit (Hct) is to get the blood to a normal consistency (viscosity), as the heart and blood vessels are designed to pump and hold a fluid close to the viscosity of water, not oil.
Once the blood volume is replete and the viscosity of the blood is normal, the red blood cells can fulfill their function of oxygen delivery to the tissues much better. The red blood cells have a fantastic capacity to increase their oxygen delivering ability by many adaptive mechanism so that, with the proper compensations in fluid replacement, your body should not be deprived of adequate circulation or oxygen.
What can I expect following initial treatment?
At the beginning of your polycythemia vera you will have an elevated hematocrit (Hct). As the initial salvo of phlebotomies are performed, the red blood cell (RBC) mass and plasma volume are reduced to normal levels. After that, depending on the rate of your RBC production and how fast you build up your red blood cell mass, it should take periodic phlebotomies to maintain your Hct at a normal level unless you are receiving other therapy which controls your counts and reduces or eliminates the need for further phlebotomies. The frequency of phlebotomy after the initial series varies widely from patient to patient and within one individual, depending on the disease activity.
Are phlebotomies dangerous?
Most patients tolerate phlebotomies rather well. Special care must be taken in patients with cardiovascular instability. Also phlebotomy may temporarily cause an increase in platelet counts.
Is there anything I can do to reduce post-phlebotomy symptoms?
Yes. The immediate post-phlebotomy period symptoms of weakness, headache, etc. are due to the acute change in blood volume. Drink plenty of fluids just before and for two days after the phlebotomy. Also, do not engage in strenuous physical activity during that time. Low dose aspirin (81 mg/day) especially pre- and post-phlebotomy is suggested to keep the platelets from being too sticky. This helps in maintaining good circulation even if there is a post-phlebotomy increase in the platelet count. This should be taken only if there are no contraindications so check with your doctor before taking aspirin.
Is phlebotomy the only treatment used?
No. In many instances, phlebotomy is used to rapidly bring down the red cell mass and then myelosuppressive drugs are added to the treatment plan. Some patients will not tolerate phlebotomies or may have such active red cell production that the required frequency of phlebotomy is unacceptable. In addition, some patients have other elevated cell lines such as high platelets or high white cell counts. Some experts use phlebotomy initially but think it speeds the process toward the spent phase. For a variety of reasons, phlebotomy is combined with myelosuppressive therapy to control very active erythrocytosis, thrombocytosis or myeloid metaplasia. Hydrea and Interferon are the drugs most frequently employed today and if elevated platelets are a problem, anagrelide may be used.
What about iron deficiency following phlebotomy?
Of necessity, if it is not replaced it will decrease. In fact, the long term objective of phlebotomy is to inhibit red blood cell production by creating a state of iron deficiency. Red blood cell production requires iron stores in the bone marrow. The iron is incorporated into hemoglobin (Hg). When iron is absent, the red blood cell parent cells (precursors) will turn out red blood cell that contain less Hg. That is why they are smaller in size and the mean corpuscular volume (MCV) is low.
It is not appropriate to replenish the iron stores if the polycythemia vera is still active because this will stimulate production of more red blood cells and raise the hematocrit and blood viscosity and you will be back where you started-needing more frequent phlebotomies.
What Is the effect of iron deficiency on your body?
At a normal hematocrit, there should be none. In the immediate post-phlebotomy period the symptoms of weakness, headache, etc. are due to the acute change in blood volume.
The state of iron deficiency in patients without polycythemia vera leads to iron deficiency anemia and when the hematocrit gets low enough they will feel weak and tired and have headaches and other symptoms. That is due to a low hematocrit with compromise of oxygen delivery. This is not the case in an iron deficient polycythemia vera patient who has a normal hematocrit.
Iron is needed for many metabolic tasks in the body, but these take priority over hemoglobin synthesis, so that the iron left in your body is usually sufficient for these needs. If your body does not need the excess red blood cells that you are making, then you are better off without them and there should be a net gain in your health status and a net decrease in your risk of thrombosis or bleeding.
What treatments other than phlebotomy have been used?
A number of older chemotherapeutic agents have been tried in the past. Past experience has demonstrated, for example, that administration of 32P (radioactive phosphorus) in doses required to achieve and maintain a normal blood count or the use of certain alkylating agents resulted in unacceptable high (20 to 30 percent in some literature reports) occurrence of newly diagnosed acute leukemia, with a peak onset of 8 years after diagnosis. In a comparison by the Polycythemia Vera Study Group between management with limited doses of 32P (5mC per year), unlimited chlorambucil, and phlebotomy alone, the incidence of acute leukemia and non haematologic malignancies was increased in both groups receiving myelosuppressive therapy by a factor of 4:1. Acute leukemia developed earlier and with a greater frequency in the chlorambucil-treated cases and was a dose-related phenomenon. In contrast, patients treated with phlebotomy alone had an incidence of acute leukemia of less than 1%. However, this group had a higher incidence of thrombosis (abnormal blood clotting) and hemorrhage (bleeding) in the first two years of treatment. This is one of the reasons why attention is focused on the agents discussed above.
Is Hydrea safer than the other agents?
Some doctors feel very comfortable with its use, some do not like to use it in younger patients who will require treatment for many years but feel comfortable using it in older patients who are unlikely to remain on it long enough to develop any secondary problems. The literature suggests that the risk of secondary leukemias is lower with prolonged Hydrea therapy in comparison to older agents.
How long do I have to take Hydrea?
Unless your doctor changes you to another treatment agent, for life. Polycythemia vera is a chronic condition. The rapid rebound following drug withdrawal requires continuous administration.
Will I still need phlebotomies if I am taking Hydrea?
Because hydroxyurea has less of a suppressive effect on erythropoiesis (red cell production ) than on platelet and neutrophil production, supplementary phlebotomies may be required for the maintenance of an optimal hematocrit.
Are there any other treatment options?
Yes, interferon has been used in the treatment of polycythemia vera (PV) and other myeloproliferative disorders (MPD) since the mid-1980’s. Some literature reports suggest that interferon is proving superior to phlebotomy and may become the treatment of choice for PV and related MPD disorders as it may offer the best option for improving the marrow status and delaying or preventing development of the “spent phase” in PV and essential thrombocythemia (ET). In Diagnosis and Treatment of Polycythemia Vera, Leukemia and Lymphoma 2000, Vol 36(3-4)pp 239-253, interferon is referred to as first line treatment for PV. But not all doctors are in agreement on this. One of the main advantage of interferon is that patients can be cycled. This agent actually improves the marrow in some patients and the improvement is lasting so they can go months to years before needing further treatment. One patient in the MPD-NET discussion group was able to go without treatment for 3 years after stopping interferon before her platelet counts started to rise. Even then, much of the improvement in her bone marrow was still seen. After a second course, studies of Dr. Joseph Prchal showed that she was polyclonal, that is there was a return of normal hematopoeitic stem cells and only a small percentage of the PV clone.
However, there is no consensus among the experts as to how long, how much and whether to stop interferon and start it again when counts rise or the spleen enlarges or whether patients should remain on a lower maintenance dose forever.
Anagrelide, an agent which lowers platelet counts, is also used in PV patients. In some cases, anagrelide is combined with hydrea.
How is Interferon administered?
Usually the patient self-administers subcutaneous shots. The dose and frequency varies depending upon the bias of your doctor. Some doctors prescribe daily injections for a period of time until there is improvement, then cut back to a lower maintenance dose for a period of time. Some use a three times a week routine. There is no agreement on dose, frequency of injection, how long patients should stay on the drug, whether they should remain on for life at a lower maintenance dose or cycle.
What side effects can I expect from Interferon?
Initial flu like symptoms are experienced by nearly everyone. Some people experience fatigue and find they have to slow down while on interferon. Some tolerate the drug better than others and are able to carry out a fairly normal routine. Others discontinue treatment.
What is post polycythemic myeloid metaplasia?
Post polycythemic myeloid metaplasia (PPMM) is also referred to as the “spent phase”. After years of hyperactivity, the marrow may become increasingly fibrotic (scarred), hematopoiesis (blood production) becomes ineffective and peripheral blood counts decrease. The marrow becomes hypocellular as opposed to the hypercellular state in the proliferative phase. During this phase, hematopoiesis may resemble that seen in aplastic anemia, sideroblastic anemia, refractory anemia, or paroxysmal nocturnal hemoglobinuria.
Some patients seem to have growth factors that predispose them to the development of fibrosis. Interferon has retarded or reversed this is some patients but is not effective in all. Bone marrow transplantation is being used at some centers to treat myelofibrosis, spent phase polycythemia vera and essential thrombocythemia as well as chronic myelogenous leukemia.
What about bone marrow transplants?
There is not much literature on this for polycythemia vera (PV) patients. Transplantion is used in PV patients who have progressed to the post polycythemic myeloid metaplasia stage, have progressed to acute leukemia, or who cannot be controlled by other therapies. Stem cell harvest and storage is being recommended for PV patients in the proliferative stage who may progress to myeloid metaplasia with myelofibrosis.
Many PV patients tend to live out normal life spans, so unless there is conversion to a more aggressive form of these diseases, bone marrow transplants are not presently considered as first line treatment.
Can I pass polycythemia vera on to my children?
There are a number of literature reports on occurrences of polycythemia vera or other myeloproliferative disorders in the same family. If you have young children, you probably should mention your condition to their pediatrician. If you have grown children, you may want to suggest that they have their blood counts checked periodically and make sure that their doctor knows of the family history.
What is essential thrombocythemia (ET)?
Essential thrombocythemia is one of the myeloproliferative diseases (MPD). It is the MPD variant which is characterized by platelet counts greater than 400,000. The MPDs also include polycythemia vera (PV), Agnogenic Myeloid Metaplasia (AMM), secondary myelofibrosis (MF) and chronic myelogenous leukemia (CML). Each of these variants have predominant features which permit classifications which are named for the cell type showing the most marked involvement. There is a great deal of overlap in the features of these various syndromes and transition from one to another is common.
Is essential thrombocythemia cancer?
No, as there are no cancerous cells. But it is considered a chronic haematological malignancy. This can be confusing, and insurance companies take varying views.
How does essential thrombocythemia fit in myeloproliferative disorders?
Thrombocythemia (or thrombocytosis) is defined as the occurrence of a platelet count in excess of 400,000 per microliter in the setting of a myeloproliferative disease. When this is the predominant abnormality, the syndrome is classified as essential thrombocythemia. Abnormal megakarocyte proliferation (platelet precursors) is seen in all variants of MPD and elevated platelet counts is common in PV, CML and the proliferative states of AMM. On the other hand, ET patients can also have elevated white cell count (WBC), hematocrit (HCT) and hemoglobin (HG) counts so a careful differential diagnosis is essential.
What causes essential thrombocythemia?
No one knows why it develops. In all of the myeloproliferative disorders, the stem cell that is capable of producing red cells, certain white cells and platelets somehow goes haywire and no longer keeps the blood elements produced by the marrow in balance. In essential thrombocythemia, the marrow produces too many platelets.
What symptoms might I experience from the essential thrombocythemia?
There are any number of symptoms that can go along with this condition. Visual disturbances when platelets are too high are experienced by many. These generally are described as “light shows” or “silent migraines”. Minor symptoms can include bruising, bleeding such as bleeding gums, nose bleeds, heavy menstrual periods, pain, tingling, burning or numbness in fingers and toes, skin sensations-tingling, feeling of something crawling on your arm, headache and fatigue. More serious symptoms can include stroke, heart attack, pulmonary embolism, thrombophlebitis (pain and swelling will be usually be present in the affected leg), hemorrhage. If myeloid metaplasia is present, the patient may have a sense of fullness in the area of the liver or spleen. There may be pain in those areas.
There are also a whole gaggle of metabolic abnormalities that go along in patients with myeloproliferative disorders. These include:
How is essential thrombocythemia diagnosed?
The diagnosis of essential thrombocythemia is primarily one of exclusion. If platelet counts are elevated with:
How do you differentiate between primary and secondary thrombocythemia?
By the criteria discussed above. If other disease states such as cancer, infection, etc. have been ruled out and the bone marrow findings are present, then the diagnosis is primary thrombocythemia.
What are some of the other names for this condition?
Essential thrombocytosis, thrombocytosis, primary thrombocytosis, essential thrombocythemia.
Can essential thrombocythemia be cured?
Essential thrombocythemia (ET) is a chronic condition. The only potential cure at the moment is a matched donor for bone marrow transplant. Most ET patients are not eligible for this procedure. Because of its associated risk and expense, bone marrow transplants are generally reserved for life-threatening diseases. ET patients generally do not fall in this category. But a lot can be done to reduce symptoms and risks of complications.
What is my probable life expectancy?
Essential thrombocythemia patients have an excellent chance of living out a normal life span if properly monitored and treated as necessary. Do keep in mind that this is a chronic hematologic malignancy and it is prudent to be monitored regularly by a hematologist, it is important to report any symptoms such as visual distrubances, unexplained pain, numbness, tingling, bruising to your physician, and for those who have had symptoms from their ET, treatment will be required. But it can be controlled, and you can live with it for a long time.
How common/rare is essential thrombocythemia?
The published annual incidence for essential thrombocythemia ranges from 0.1-2.4/100,000. It is rare and is classified as an orphan disease.
Do patients just have elevated platelet counts?
In essential thrombocythemia (ET), in addition to elevated platelet counts, platelets generally can be abnormal in size, shape, density and function. Spontaneous aggregation (clumping) can occur putting ET patients at higher risk for clotting events. There can also be an increased risk of bleeding. According to Dr. Gilbert, clinical manifestations are dominated by hemorrhage (bruising, nosebleeds, unexplained gastrointestinal bleeding, and postoperative hemorrhage) and microvascular occlusions erythema (redness) and burning as well as a host of neurological complaints such as headache, parathesis-numbness and tingling and transient ischemic attacks.
It also is not uncommon for all myeloproliferative disorder patients to have other elevated blood counts. For example, in addition to high platelet counts, white cell counts may also be increase.
Am I at risk if my platelets are elevated?
The answer is a definite maybe. Platelet counts alone are not predictors of complications. Elevated platelets can present a risk of thrombosis (abnormal blood clotting) or bleeding. Elevated platelets can also cause excessive bleeding during surgery and your physician is likely to want to reduce platelet counts before surgery. But this is not a monolithic, everyone acts in a predictable fashion kind of disease. You can go on the principal that risks are increased if platelet counts are elevated and then work with your doctor based on your own disease course and whether or not you are symptomatic or have independent risk factors that can complicate the course of your disease.
How is essential thrombocythemia treated?
This depends upon the patient and whether there have been symptoms or complications. The current treatment options include nothing, baby aspirin, interferon, anagrelide or hydroxyurea alone or in combination. At present Bone marrow/stem cell transplant is being evaluated in an MPD-RC clinical trial (MPD 101) as a possible cure.
Will I need a bone marrow biopsy and what are these like?
Yes. Patient experience varies. Basically, you lie down on your stomach and a special needle is used to drill into the hip bone and extract a core of bone and an aspirate of the marrow contents. Before the procedure, a local anesthetic is injected to numb the bone. But there is no way to numb the interior marrow so there will be momentary sharp pain. This procedure can be made much more comfortable by insisting that the doctor wait until the local has had a chance to take effect. Taking a mild tranquilizer about an hour before the procedure can reduce anxiety and make the procedure more comfortable. Finally, some doctors will use a combination of intravenous drugs (demerol and versed, demerol and ativan, morphine and valium) which allows the patient to sleep through the procedure. Either way, this is an outpatient procedure usually performed in your hematologists’ office.
What are the criteria for starting treatment?
This may vary from physician to physician. Generally, if the patient is not experiencing any problems from their essential thrombocythemia, baby aspirin (unless the patient tends to bleed) may be the only treatment suggested along with close monitoring. If a patient presents with a stroke, heart attack, thrombophlebitis, clearly reduction of platelet counts will be deemed necessary to get them out of danger and reduce the risk of further complications and treatment will be started immediately. If a patient shows up with enlarged spleen or liver which means that you have blood production taking place outside the bone marrow, treatment is a very good idea. When symptoms are “minor”, treatment may still be appropriate both for comfort and to help slow disease progression.
What do people with essential thrombocythemia die of?
In most cases, if they are properly monitored and treated, diseases of old age. A small percentage may convert to acute leukemia. This is usually associated with prior treatment of a leukemogenic drug (a drug that, as a side effect, may initiate or progress leukemia). Some persons progress to the post thrombocythemic myeloid metaplasia stage where blood counts fall and bleeding and infection complications become a problem.
Are there any symptoms/occurrences that signal a change or progression?
One of the reasons it is important to be monitored and to have periodic bone marrow evaluations is that changes can take place in the bone marrow that are not readily apparent by looking at blood counts or how the patient feels.
If there is a sudden change in your blood counts, or a gradual shift in either direction, or you start having symptoms that weren’t there a short while ago, such as bruising, headache, fatigue, swelling in your legs or abdomen, visual disturbances, headache, unexplained pain, numbness etc., find out what is going on. We also have to remember that having essential thrombocythemia does not give us a free pass on other diseases. Some will convert to polycythemia vera for example.
Does essential thrombocythemia ever affect children?
Do children with essential thrombocythemia react any differently than adults?
This was originally thought of as a disease of old age and symptoms were largely ignored in younger patients until the last decade or so. So there isn’t much in the literature about childhood essential thrombocythemia T and most of it simply reports treatment with anagrelide.