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Polycythemia vera (PV), or Polycythemia rubra vera, is one of the Myeloproliferative Neoplasm Disorders (MPN). In this variant, there is uncontrolled production of mature red cells leading to an increase in the red cell mass, resulting in abnormally high hematocrit (Hct) and hemoglobin (Hg). This causes an increase in blood volume and viscosity which can lead to complications involving thrombosis, eg heart attack, strokes, or other clotting or bleeding episodes, if not controlled. The MPNs also include essential thrombocythemia (ET), agnogenic myeloid metaplasia (AMM), also known as idiopathic myelofibrosis (IMF), secondary myelofibrosis (MF) following PV or ET, 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. This is discussed in greater detail below. PV is fairly rare, being diagnosed at a rate of 1 to 2 new cases per 100,000 per year, and is considered an orphan (rare) disease. Because of its rarity, and the fact that it is a chronic condition (most PV patients live a long time), it hasn't been studied the way "major" diseases have. You will find that many hematologists/oncologists (hem-oncs) may have little experience with PV and may not be aware of new developments in treatment of the disorder. For this reason a consultation with an expert at a major institution may be warranted.

We hope that the information in this FAQ, in the MPN-NET online discussion group, in the MPN VOICE newsletter and on the MPN web page will help newly diagnosed PV patients sort this all out. Further details of these additional resources are given in Question 33.

2. What is MPN (myeloproliferative neoplasm)?

"Myelo" is the Greek word for marrow "Proliferative" means growing or reproducing "Disease" is the improper function of a body organ. MPN is literally "Marrow Proliferative Disease" or improper function of the bone marrow organ.

Bone marrow is the body's blood-forming (hematopoietic) organ. It contains blood-forming cells called "pluripotent hematopoietic precursor or stem cells" (PHPC) that have two important functions. (1) self-renewal to maintain a pool of stem cells for future proliferation or growth. (2) 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), several varieties of white blood cells (WBC), and platelets. 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 hematopoietic 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 they appear in the blood in their proper proportions.

In MPN, one abnormal PHPC clone has a growth advantage that allows it to reproduce more aggressively than the normal master stem cells, and eventually these abnormal clones take over the marrow. 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 MPN involves the improper balance between production of different blood cell types just as much as it involves abnormality of any given blood cell type.

3. Where Does Polycythemia Vera Fit in?

In PV, the PHPC clone (stem cells responsible for blood production) produce too many red blood cells which literally causes the patient to have "too much blood". The resulting increased blood volume and thickness (viscosity) leads to an increased risk of the patient experiencing a thrombotic (clotting) event. Platelets and white cells may also be overproduced, but PV is the only MPN variant in which there are too many red cells. The risks of complications can be reduced by appropriate treatment.

4. 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 1213 PV patients followed for 20 years, the highest numbers were in the 51-75 age groups. (The ages ranged from under 10 to over 90). See “Polycythemia 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.

5. What causes Polycythemia Vera?

Genetic studies suggest that the appearance of the abnormal stem cells in a person with PV is due to a mutation in a gene or genes in a single cell. The trigger for this is not understood, but as in cancer and leukemia, agents like radiation or toxic chemicals (eg benzene) may be suspected in some cases. For most of us it is not possible to track down a specific cause.

6. What are the Symptoms and Risks?

PV is insidious in onset and may be present for 1 to 2 years before medical attention is sought. During the asymptomatic phase, PV may be discovered at the time of a routine examination which reveals an elevated hematocrit. PV 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). Blood clotting (thrombosis) and bleeding (hemorrhaging) are big problems at the outset, especially before diagnosis, but once blood counts are properly controlled, risks are reduced. High platelets can compound the risks related to high hematocrit and hemoglobin. 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, commonly felt as a feeling of fullness in the head), headache, dizziness, visual disturbances, severe itching (pruritus), particularly after a bath or shower, an inability to concentrate, and numbness (paresthesia). Related findings at diagnosis can include high blood pressure (hypertension), a high cardiac output state, and areas of little or no blood flow (vascular stasis). Significant arterial or venous thrombosis occurs in one third to one half of uncontrolled cases, and these events may precede the diagnosis. They include heart attack, stroke, pulmonary embolism, deep vein thrombosis, and portal vein clots (veins leading to liver), etc.

7. 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 modified guidelines of the Polycythemia Vera Study Group and run a series of diagnostic tests. If the Study Group findings are present, then a diagnosis can be made with certainty. Therefore, certain physical and laboratory findings are believed critical by many doctors to reach a diagnosis of polycythemia vera. Differential diagnosis from relative polycythemia due to abnormalities in plasma volume from, for example, dehydration, rather than red cell production, requires the demonstration of absolute erythrocytosis (elevated red cell count) by direct measurement of red cell mass and plasma volume. Once an elevated red cell mass is documented, polycythemia vera must be distinguished from conditions producing isolated erythrocytosis. However some doctors feel that determining erythropoeitin levels is an appropriate indicator if the value is below 4. Researchers at Mayo Clinic have developed a more sensitive test for this purpose.

The criteria that must be met for a diagnosis of PV, and the incidence of these abnormalities at diagnosis, are: an increased red cell mass and an enlarged spleen (splenomegaly, which is present in 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. In PV 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 which will multiply in the absence of the hormone erythropoietin, EPO (increases in red cell numbers are normally triggered by EPO production by the kidneys), and there is a marked increase in the number of erythroid colonies formed with the addition of EPO (increased EPO sensitivity). More recently, a test for the recently identified JAK2V617 mutation present in most PV patients has been developed. This does not replace other diagnostic tests but is complementary to them.

8. What causes Complications?

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), erythromelalgia (pain in fingers and toes), or even gangrene 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), hemostasis (stagnation of blood due to 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.

9. How Do I Reduce the Risk of Complications?

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 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 among different hem-oncs and you should always discuss this with your own doctor. Most experts now adopt a target hematocrit of below 42 in women and below 45 in men, eg in the authoritative article by Michiels J.J., Barbui T., Finazzi T., Fruchtman S.M., Kutti J., Rain J-D., Silver R.T., Tefferi A., & Thiele J., 2000: Diagnosis and Treatment of Polycythemia Vera and Possible Future Study Designs of the PVSG. (In: Leukemia and Lymphoma, 2000 Vol.36(3-4),pp.239-253). This paper also states that platelet counts should be maintained below 400 (x109/litre). Treatment options also vary depending upon the particular circumstances of each patient.

10. What Else Might I Experience With PV?

There are a number of other metabolic abnormalities which occur in MPN patients, including patients with PV.MPN patients may exhibit high uric acid levels (hyperuricemia, 50%) which can lead to joint pain and gout, low cholesterol levels (hypocholesterolemia), high histamine levels occur in two thirds of MPN patients which can produce itching (pruritus), heartburn, acid reflux/belching, peptic ulcer, painful small bowel action (hypermotility), flushing and allergic rashes. Hypermetabolism is commonly manifested as weakness and fatigue that occur in MPN patients not experiencing anemia.

11. How is Polycythemia Vera Treated initially?

Phlebotomy (called venesection in some countries) is the most common initial treatment for most polycythemic patients. It is done to reduce the red blood cell mass (RBC mass) — that is, the total number of circulating red blood cells. It is generally done weekly, until the hematocrit (Hct) is reduced to an acceptable level. The target level for Hct is 45 in men and 42 in women.

Phlebotomy is a way of rapidly reducing the volume of red blood cells down to normal levels. 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 red cells varies widely, and can be much faster, or slower, than this.

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. Within a day or so 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 transmit a fluid close to the viscosity of water, not oil. You can imagine what would happen if you filled your water tank and plumbing system with motor oil instead of water! The patient’s risk of experiencing a thrombotic event increases progressively as the blood becomes more viscous (ie, if the Hct is above 42 in women or 45 in men). Once the blood volume and viscosity are normal the red cells can fulfill their function of oxygen delivery to the tissues much better. The red cells have a fantastic capacity to increase their oxygen delivering ability by many adaptive mechanisms so that, with the proper compensations in fluid replacement, your body should not be deprived of adequate circulation or oxygen.

12. What Can I Expect Following Initial Treatment?

At the beginning of your PV you will have an elevated hematocrit. As the initial round of phlebotomies is performed, the RBC mass and plasma volume are reduced to normal levels. The number of phlebotomies required varies widely – from one or two up to ten or more. After that, depending on the rate of your RBC production and how fast you build up your red blood cell mass, you will need 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, but is also limited by the amount of iron available, either from absorption from food or from recycling (see Questions 16, 17). Experts feel that if you require more than 8 phlebotomies per year, after the initial series, or your platelets are above 400, or you have had a prior thrombotic event or you have spleen enlargement and/or marrow fibrosis, or are symptomatic, or at risk for cardiovascular events, then myelosuppresive (ie drug) therapy is necessary.

If a phlebotomy is carried out when the Hct rises to 45 in a male, or 42 in a female, the Hct will commonly drop by around 3 points, ie to 42 for men and 39 in women. Many patients feel more comfortable at these levels.

13. Are Phlebotomies Dangerous?

Most patients tolerate phlebotomies rather well. They are no different from a blood donation, except that the blood should not be reused. Special care must be taken in patients with cardiovascular instability, for instance by administering saline solution before or during the phlebotomy. Phlebotomy causes an increase in platelet counts and white cell counts in many patients as a result of iron deficiency, and this may require further adjustment to treatment. Studies by the Polycythemia Vera Study Group (PVSG) showed that patients treated with phlebotomy alone had a very low incidence of acute leukemia compared to treatment by alkyating agents and radioactive posphorus (no longer in common use because of their leukemogenicity - see Q 18). However, the phlebotomy group had a higher incidence of thrombosis and hemorrhage in the first two years of treatment. This is one of the reasons attention was focused on the agents discussed in Q 18, 19.

14. Is there anything I can do to reduce post-phlebotomy symptoms?

Yes. Some patients experience immediate post-phlebotomy symptoms of weakness, headache, etc. 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 enteric-coated 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. Patients should check with their doctor before taking aspirin, particularly if taking other drugs such as coumadin (warfarin).

15. 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, or even replace phlebotomies, as the primary treatment. Some patients do 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, even before phlebotomy. 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 red cell or platelet production, and myeloid metaplasia (the production of blood cells in organs other than the bone marrow). Hydrea and Interferon are the drugs most frequently employed today. If elevated platelets are a problem, anagrelide (Agrylin) may be used, although a recent trial on high risk patients has shown that this drug may increase the risks of bleeding, and in some patients more rapid development of bone marrow fibrosis.

16. What about iron deficiency following phlebotomy?

Of necessity, if iron is removed (in hemoglobin) during phlebotomies and 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 make cells that contain less Hg. That is why they are smaller in size and the mean corpuscular volume (MCV) is low. In your complete blood count (CBC) a lower than normal MCV is a very good indicator of iron deficiency. The term that describes these smaller-than-normal cells is microcytosis. It is generally not appropriate to replenish the iron stores if the PV is still active because this will stimulate production of more red blood cells and raise the Hct and blood viscosity and you will be back where you started — needing more frequent phlebotomies. The exceptions to this are when too many phlebotomies, or internal bleeding, causes anemia. Such situations may indicate the need for temporary use of an iron supplement. Although iron supplements should usually be avoided, it is generally not necessary to limit iron intake in our diets, as most of us absorb only small quantities of iron from our food.

17. What Is The Effect of Iron Deficiency On Your Body?

At a normal hematocrit there should be none, although many patients report a feeling of fatigue. In the immediate post-phlebotomy period the symptoms of weakness, headache, etc. are due to the acute change in blood volume.

If your hemoglobin and hematocrit fall below “normal” levels (ie below the reference range specified by the lab in which the counts were done), you may develop iron deficiency anemia. This can lead to symptoms such as shortness of breath, weakness, and fatigue, headaches and other symptoms. This is due to a low hematocrit with compromise of oxygen delivery. The aim of phlebotomies is to reduce the iron so that the Hct and Hg drop to acceptable levels, but not so low that the person becomes anemic. It is a fine balance!

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.

According to one specialist, the late Dr. Harriet S. Gilbert, you should be cheered by reports that iron contributes to cardiovascular and coronary heart disease, and that iron deficiency may protect against heart attacks. Your phlebotomies may be doing more than just correcting your blood viscosity and might actually be contributing to your increased survival. Dr. Gilbert has mentioned that she has often wondered why some patients with PV and all the risks that the disease poses have a close to normal life expectancy. It certainly suggests that there are factors at play that prolong life, although overall life expectancy is somewhat reduced.

18. What Other Treatments Have Been Used?

A number of older chemotherapeutic agents have been tried in the past to "unrev" the marrow and lower counts. Past experience has demonstrated, for example, that use of a class of drugs called alkyating agents, or administration of 32P (radioactive phosphorus) resulted in unacceptable high (20 to 30 percent in some literature reports) incidence of acute leukemia. The time of peak onset was around 8 years after diagnosis for 32P. In a comparison by the Polycythemia Vera Study Group (PVSG) between management with limited doses of 32P (5mC per year), unlimited chlorambucil, and phlebotomy alone, the incidence of acute leukemia and non hematologic 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, and resulted in abandonment of chlorambucil treatment. 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 and hemorrhage in the first two years of treatment. This is one of the reasons attention is focused on the agents discussed above.

19. What are the Present Treatment Options?

Hydroxyurea, anagrelide, and Interferon are used, either instead of, or supplementary to, phlebotomies, and trials of a relatively new drug, Gleevec, are continuing.

20. How Long Will I Have to Take Hydrea or other drugs?

Because PV is a chronic condition, indefinitely, unless your doctor changes you to another treatment agent. Blood counts generally rebound rapidly once HU is stopped, whereas a period of remission is sometimes experienced after stopping Interferon.

21. 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 (a type of white blood cell) production, supplementary phlebotomies may be required for the maintenance of an optimal hematocrit, but this varies considerably between individuals.

22. Is Interferon a good option?

Interferon has been used in the treatment of polycythemia vera and other myeloproliferative disorders since the mid-1980's. Some literature reports suggest that interferon is proving superior to phlebotomy alone or with HU or anagrelide, and may become the treatment of choice for PV and related MPN 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 ET. In Diagnosis and Treatment of Polycythemia Vera, Leukemia and Lymphoma 2000, Vol 36(3-4)pp 239-253, Michiels and others refer to interferon as first line treatment for PV, although not all doctors would agree with this. One of the main advantage of interferon is that patients can be cycled, ie a patient may benefit from several months on, then off, the drug. 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. 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 indefinitely. Interferon, like HU, is not without potentially serious side effects. These include depression, under active thyroid gland (hypothyroidism), overactive thyroid (hyperthyroidism – less common), and neuropathy.

23. How Is Interferon Administered?

At present, interferon for Myeloproliferative Neoplasm Disorders is administered by injection; usually the patient self-administers subcutaneous shots. The dose and frequency varies depending upon the bias of your doctor. Some hem-oncs 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. This is frustrating for patients who need to review the literature and discuss their options with their hem-onc. Results are what are important.

24. What Side Effects Can I Expect from Interferon?

Initial flu like symptoms are experienced by nearly everyone, but this can be reduced or eliminated by starting at a small dose and slowly ramping up to the therapeutic target dose. Some have also reported that they suffer few side effects with the pegylated dosage form, Pegasys (see Q25). Tylenol (acetaminophen, called paracetamol in some countries) controls these flu-like symptoms and they subside as the body adjusts to this medication. 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. 20-30 percent discontinue treatment due to side effects. We have a number of people on interferon in our MPN-NET discussion group who will be happy to discuss this issue with you. Your doctor should give you written information about side effects and the package literature also lists reported side effects.

25. Are there types of Interferon which don’t need to be injected?

Trials of oral interferon (tablet form) have shown mixed results; trials are continuing but their outcome is not yet known. A promising alternative form, although still injected, is called “pegylated interferon”. By changing the chemical makeup of the drug to a slower release longer-lasting form, injections are needed only once a week instead of several times a week or even daily. Two brands, Pegasys, and Peg-Intron, are currently being trialed, and anecdotal reports from patients on these are encouraging.

Gleevec (imatinib mesylate), a drug developed to target the abnormal chromosome in chronic myelogenous leukemia (CML, another MPN), has been trialed in other MPNs, including PV. Initial trials have yielded mixed results, although a high proportion of those in the trials had a reduction in phlebotomy requirement. It appears not to help in lowering platelets, and the side effects can be significant (eg fluid retention – edema – diarrhea, nausea and fatigue). Trials are continuing.

Yes! Research in several laboratories over the past couple of years has revealed a mutation in a gene within a very high proportion of subjects with PV. The particular gene, on chromosome 9, is called JAK2V617F, often referred to as the JAK2 mutation. This has stimulated further research — into development of drugs which might target this faulty gene and reduce the over activity of the bone marrow in those with PV. This is a most exciting development and one which holds great promise for many of us. Not everyone with PV is shown to be JAK2 positive – current results show that 70-90 percent are, although more sensitive testing methods may yield a higher percentage than this. At present the knowledge of whether you are JAK2 positive or JAK2 negative will make no difference to your treatment, as the research into new treatments has only just begun. Many larger teaching hospitals and research institutes are now testing their PV patients for the JAK2 mutation, in the expectation that within a few years new drugs will be developed.

28. 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 or scarred (myelofibrosis), hematopoiesis (blood production) becomes ineffective and peripheral blood counts decrease, and the spleen usually becomes enlarged. The marrow becomes hypo cellular (fewer blood-forming cells) as opposed to the hypercellular (many blood-forming cells) state in the proliferative phase. During this phase, hematopoiesis may resemble that seen in aplastic anemia, sideroblastic anemia, refractory anemia, or paroxysmal nocturnal hemoglobinuria. As the condition worsens, constitutional symptoms such as fatigue, loss of appetite, weight loss, and night sweats may increase. Some patients seem to have growth factors (at a cellular level) that predispose them to the development of fibrosis. Interferon has retarded or reversed this in some patients but is not effective in all. Bone marrow transplantation is being used at some centers to treat myelofibrosis, spent phase PV and ET as well as CML.

Because PV is a chronic disease most of us will live for many years provided our treatments are working well. A bone marrow transplant (BMT) carries very high risk and is therefore not generally used unless other treatments have failed, or the patient progresses to PPMM (“spent phase”) or acute leukemia. BMT is thus an option primarily for advanced disease, with several major centers (Fred Hutchinson Cancer Center, City of Hope, MD Anderson) having the most experience with such transplantation in the US. Stem cell harvest and storage has been carried out by/for some PV patients in the proliferative stage, in the hope that should their disease progress to PPMM, then an autologous transplant using their own stem cells will “turn the clock back”. There is no general agreement on the value of this, and many hematologists argue that newer techniques for allogeneic bone marrow transplants (ie, using stem cells from another, suitably matched, person) are preferable. One such technique is that of “mini-transplants” (or “reduced intensity conditioning”), wherein the cells in the marrow of the patient are not totally destroyed prior to the infusion of the donor cells. This seems to result in fewer side effects and better outcomes, and offers hope for older patients.

There is information on bone marrow transplants in the MPN-net archives and you can contact list owners of MPN-NET to enquire about new developments. Excellent information is available on the BMT Information website at www.bmtinfo.org. There is also information through the ACOR BMT-TALK support group.

Some PV patients are bothered by itching (pruritus). One of Dr. Gilbert's earliest research studies in PV dealt with this issue. She has written " I found that it was the result of histamine release by the basophils”. Basophils are the type of segmented white blood cells produced by the bone marrow precursor involved in PV. An increased number of basophils are produced and they do maintain their function, as do most of the cells produced in the PV marrow. Basophils produce and release histamine in response to many stimuli. In PV the most common stimulus is exposure to water — hot or cold, depending upon the patient. Thus, post-bathing or post-showering pruritus is common. Exposure to air, as after removing clothing, is another common stimulus. Histamine and related substances released by the basophils may also contribute to the higher incidence of upper gastrointestinal (GI) problems, such as ulcer and gastritis seen in PV. (Histamine stimulates the release of hydrochloric acid in the stomach.) Histamine may also produce diarrhea and increased bowel motility. For pruritus, you can start with mild antihistamines such as Benadryl® diphenhydramine hydrochloride antihistamine (or your doctor may prefer some of the newer agents) taken one-half hour before exposure to whatever brings on the itching. If the trigger is bathing, it is best done at night, since Benadryl can make you drowsy. You can work up to one of the histamine type I blockers such as Seldane® (terfenadine), Claritin® (loratadine) or hismanol which can be taken during the day, as they do not make you sleepy. If itching is still a problem, the stronger antihistamine, Periactin® (cyproheptadine) can be tried at night and in low dose because it can also cause drowsiness. One patient in the MPN-NET group has mentioned his allergist gave him "zyrtec" which has been tested in Europe and he says works well for him. For increased acidity, histamine type II (H-2 blockers such as Zantac® (ranitidine hydrochloride) and antacids may help. Many PV patients with GI symptoms take one of the newer PPI (proton pump inhibitor) drugs such as Losec or Nexium. These are very effective, but you should consult your doctor about using any of the above measures to combat pruritus and GI symptoms. Ultraviolet (UV) light therapy is also beneficial for some pruritus sufferers. This should be done under the guidance of a dermatologist, although some patients report that simply being in the sun reduces their itching (although normal precautions against excess sun exposure need to be observed!). Some specialists have also found the use of the antidepressant paroxetine (a selective serotonin-reuptake inhibitor, or SSRI) is helpful, although its mode of action is not known.

If none of the supportive measures work, pruritus is an indication for myelosuppressive therapy, since fewer basophils will be produced and less histamine will be released. Some patients report a lessening of symptoms after switching from phlebotomies to either HU or Interferon. Because pruritus can be such a debilitating problem, the MPN-NET list owners have compiled a file of suggestions and remedies that list members have found useful to combat itching. It is available to members who write to
mpd-net-request@listserv.acor.org

31. Can I Pass PV On To My Children?

There are a number of literature reports on occurrences of PV or other Myeloproliferative Neoplasm Disorders in the same family, and it appears likely that the tendency to develop an MPN is inherited. 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. There is an article by Dr. Harriet S. Gilbert on our web page about familial occurrences at MPN-NET. Most cases of PV, however, appear not to be inherited; they are sporadic in nature – ie just one family member develops the disease.

32. Will having PV affect my life expectancy?

In the past, unrecognized PV led to illness or death as a result of thromboses, eg heart attacks, strokes, and other clotting episodes, and less commonly due to hemorrhaging. Although treatment by phlebotomy reduced many such instances, it was still associated with a higher risk of thrombosis. Older myelosuppressive treatments such as chlorambucil and 32P also led to a higher incidence of acute leukemia. Thus either the disease or the treatment led to a lower life expectancy. The advent of treatment by HU and Interferon has led to a reduction in thromboses, and an increase in life expectancy. A recent retrospective study of patients treated for PV in a single institution in Italy (Passamonti et al, 2004. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. American J. of Medicine, 117(10), 755-761) showed that there was indeed a somewhat lower life expectancy, but studies such as this always include some no-longer-used treatments, and we are optimistic that many of us will live out a normal life span. Don’t be too worried by some of the short life expectancy figures that you may see in older publications. These are likely to include patients subjected to outmoded treatments, and do not represent the life expectancy a newly diagnosed patient can look forward to. Remember also that they are commonly median life expectancies — ie half of the subjects in the study will live longer than the median figure!

33. Where Else Can I Go for Information?

MPN-NET internet support group

MPN-NET is a member of ACOR (Association of Online Cancer Resources), which maintains email-based support groups for over 100 different types of cancer, leukemias, and related diseases. To join MPN-NET, which has over 2300 patients from 40 countries (and growing rapidly), address an email to

listserv@listserv.acor.org

Leave the subject line blank, and in the message body, put the words: subscribe MPN-net and your first and last names Alternatively, you can write to the list-owners of MPN-NET at MPN-net-request@listserv.acor.org and ask to be subscribed to the list. Make sure you include your first and last names.

PV-FAQ as an email If you wish to obtain this FAQ as an email, write a message addressed to: listserv@listserv.acor.org

leave the subject line blank, and in the message body write:

get mpd-net.pv-faq

No signature is needed.

PV acronyms A file containing explanations of many of the abbreviations used in this FAQ, and by many subscribers to:

MPD-NET, can be obtained as an email by writing to: listserv@listserv.acor.org

leave the subject line blank, and write:

get MPD-NET.acronyms

No signature is required.

MPN web page Our group's patient-created web page is at: http://www.mpninfo.org
It has a wealth of information and links to a number of sites on the internet, where you can find even more information if you wish. Information on MPN VOICE, the newsletter of the MPN EDUCATION FOUNDATION can also be found on the website, or by writing to:

PO Box 4758
Scottsdale, AZ 85261 USA.

Most recent revision July 2006. You may make a copy of this FAQ for your personal use or to share with your family or doctor.

You may make a copy of this FAQ for your personal use or to share with your family or doctor.

Patient Recommended doctors list.
Larry Milnes, our MPN-net online support group emeritus list owner developed a list of doctors who are experts in MPNs. There are two parts to the list:

1) A list and contact information for the experts in mpns
2) A list and contact information of patient recommended hematologists.

The duty listowner can give you contact information if you write to the following address:

The list is now maintained by Bob Swanson, and any updates or new references can be sent to Bob at