International MPN News, Science & Opinion

MPNclinic…November 15, 2012

  MPNclinic   MPNclinic   MPNclinic   MPNclinic


Dr. Richard Silver

Dr. Srdan Verstovsek
MD Anderson

Dr. Ruben Mesa
Mayo Clinic

Dr. Claire Harrison
Guy’s & St. Thomas;

Dr. Attilio Orazi

Dr. Ross Levine
Sloan Kettering


Dr. Jason R. Gotlib,

Questions may be sent to

Jason Gotlib =JG Claire Harrison= CH Ross Levine = RL Attilio Orazi= AO

Ruben Mesa = RM Richard Silver= RS Srdan Verstovsek= SV John Mascarenhas=JM

(Links to earlier MPNclinic pages can be found at the end of the Catalog, here)

Welcome Guest Panelist; Dr.John Mascarenhas

      Dr. John Mascarenhas is a clinical investigator
     in malignant hematology with a focus in translational
     research involving the Myeloproliferative Neoplasms.
     Dr. Mascarenhas is primarily responsible for the clinical
     trials arm of the Mount Sinai School of Medicine
     Myeloproliferative Disorders Program
     headed by Dr. Ronald Hoffman.
MPNclinic is a forum for MPN patients and caregivers to present questions to a roundtable of hematologists and scientists. Responses from doctors are informative and educational and not intended to replace or modify medical advice offered to any reader by his or her physician.

 Signs of developing leukemia or lymphoma

63. Bonnie Evans, Georgia…When does the MPN physician request a consultation with a leukemia or lymphoma expert? What are the signs that the patient has developed leukemia or lymphoma?

RL: In most cases, the MPN expert will know what to look for if there is concern patients develop leukemia, including changes in blood counts, new infections, or changes in medication sensitivity.  They will be able to perform the needed tests, and in most cases treat the patient as needed in that case.  Lymphoma does not evolve from a MPN, and in most cases the MPN doctor will refer to a lymphoma expert.

RM: First, a transformation to lymphoma in an individual with an MPN would be an unlikely event, at least not a natural progression from earlier having an MPN.  People with MPNs clearly can develop other cancers and lymphomas are not protected from developing an illness like this, but the natural progression of the disease would be more toward an acute myeloid leukemia.  The major signs of this would be worsening blood counts and increasing blasts in the peripheral blood or in the marrow, especially to a level in the blood or marrow of over 20% blasts.

Eye disease and PV or HU

64  Bonnie Atkins …Can having PRV or taking HU affect ones eyesight or cause eye diseases?

RM: I am not aware of any direct effect that P vera or Hydrea have on eyesight.  There are individuals that have had unusual blood clotting events to the blood vessels involving the eye and this could impact vision; likewise, individuals that have had stroke related with PV could impact vision, but these are not the common occurrence

SV: Uncontrolled, high blood cell count in PV can affect blood flow in any part of the body, including in the eyes, and one may have symptoms, affecting eye sight. HU very rarely causes mucosal ulcers, and they are usualy in the oral cavity, not in the eyes. New diseases of the eye are not caused by the PV or HU.

  Elevated counts, should I consult MPN hem?

65. Allison Carroll…Short version 34 years ago at age 6 I had to have regular phlebotomy as my blood was too thick, that’s all my mum can remember they said. This lasted for a few months then my blood leveled out and no other thought was ever given to it until three months ago.

I have suffered with pain since my twenties and battled throughout to get anyone to listen to me, always being quoted I’m too young, it’s because I just had a baby, miscarriages, that I have mild osteoarthritis and a whole host of other reasons. However in 2009 after a gp change I finally got referred to a rhematologist who did extensive tests and decided I have fibromyalgia… Three months ago I had my yearly blood test due to my high blood pressure … my levels, were HCT:0.475 HGB:15.8 RBC:5.09.

My Dr at present mentioned that it sounded as if I could have PV and had it as a child but that she would just monitor my bloods and if my HGB got higher that 17 she would consider phlebotomy the same as I had as a child.

My bloods were taken again this week and were HCT:0.434 HGB:15.1 RBC:4.75 WBC:8….My question(s) is should I request to see a haematologist based on my past history as a child and the borderline FBC results, is it possible it isn’t fibromyalgia but PV causing my symptoms?

SV: Diagnosis of PV has become relative straight forward process these days. A visit to a hematologist would easily address the question and institute treatment plan, if PV has been confirmed. If not confirmed then that would eliminate any doubts. I would see the hematologist.

RM: What you describe is a complicated situation that is truly not best answered in this sort of forum.  Trying to delineate what is the correct diagnosis, how it is impacting your symptoms and how best to manage you would best be done visiting with a qualified hematologist or an MPN expert.  I advise you to speak with your friends on the list or an MPN clinic to see who in your area would be best for you to see.

RS:  There is a slight increase in the frequency of leukemia and lymphoma in patients with MPNs.  However, an experienced MPN physician can easily detect the development of these complications and therefore usually is not necessary for the patient to worry about such an event occurring undetected.  Indeed, our patients should be reminded that MPN physicians are board certified in hematology, medical oncology and internal medicine and if it is a little low grade lymphoma, they may not consider it necessary to refer a patient to a so called lymphoma or leukemia expert.  Hydrea has many side effects, but eye disease per se is not one of them.  It should be noted, however, that patients receiving interferon have reported to have a co-existent of macula degeneration.  Whether this is related to interferon or this is because macula degeneration and polycythemia vera occurs in the same age group is undetermined.  I follow the rule in the few patients who have developed macula degeneration on interferon therapy of discontinuing the interferon just to be safe.

Should I try Ruxo?

66.   Haydn Jones  I am a 59 year old male diagnosed last October with primary myelofibrosis and currently under haematology and transplant team at Leicester royal infirmary  England U K.

I am at a crisis at the moment as Prednisolone has helped maintain my blood levels but I am told I cannot be on this for much longer. I continue to lose weight and my night sweats are increasing so haemotology have concluded that I need to have a bone marrow transplant. I am due to see transplant team on the 21st August. Today at haemotology there was some question about the size of my spleen (last measured 19cms approximately 2 months ago) as this can hamper the transplant success. The haemotology doctor would like me to trial a Jak-2 inhibitor Ruxolitinib but a side effect of this drug can be anemia which could make me transfusion dependent, my transplant doctor has told me he did not want me to have too many transfusions as this could cause more complications. Investigations 06/07/2012 Haemoglobin 10.7 White cells 26.6 Neutrophils 19.9 Platelets 547

JM: Ruxolitinib is a reasonable treatment option for MF patients with splenomegaly and/or MF related symptoms. The drug was approved in the US November 2011 for the treatment of intermediate/high risk MF patients with symptomatic splenomegaly or MF related symptoms (constitutional symptoms, bone pains, fatigue, etc).  The dose limiting toxicity is thrombocytopenia and most patients will experience a reduction in hemoglobin and platelet count. The drug is generally well tolerated and headache, dizzy spells, and bruising were the most common non-hematologic adverse events noted in treated patients and were low grade events.  The COMFORT-1 (USA and Canada) and the COMFORT-2 (Europe) trials compared ruxolitinib to either placebo or best available therapy, respectively.  The ruxolitinib treated patients in both trials experienced significant reduction in spleen volume and significant improvement in symptoms. Although this drug is not curative and has not been shown to improve the bone marrow abnormalities or significantly reduce the JAK2V617F mutational burden, it has been shown to reduce markers of inflammation and improve quality of life and performance status of patients. The drug is not appropriate for patients with very low platelet counts (<50,000), and should be given at low doses (5mg twice daily) for platelets in the 50-100,000. Patients need to be followed carefully for changes in their blood counts and some patients may even require red blood cell transfusions at least initially within the first 3 months as the drug dose is adjusted. There are clinical trials that will soon open within the MPD-RC evaluating the role of ruxolitinib prior to stem cell transplant in order to reduce the spleen size and improve the performance status and hopefully this will improve engraftment and overall outcome.

Patients that have not needed RBC transfusions are less likely to develop alloantibodies (antibodies that your body make directed against donor red blood cells) that can potentially affect engraftment of the donor marrow cells. Having said this, it is not an absolute contraindication to receive RBC transfusions if clinically warranted prior to transplant and most MF patients that undergo transplant have received transfusions previously. Also highly transfused patients (>20units) begin to run the risk of developing iron overload and this may affect blood cell development and cause end organ damage (heart, pancreas, liver, thyroid) in patients. Sometimes iron chelation (medications that bind and remove iron) is employed either before or after the transplant for this reason.

In your case I would not eliminate the option of ruxolitinib even if you will ultimately go to transplant as the drug dose can be titrated to avoid incurring excessive anemia and transfusion requirements.  The possible beneficial effects of the drug beyond reducing the spleen and constitutional symptoms, may include improving your weight, energy level and endurance

SV: Use of ruxolitinib before the transplant is very good suggestion, to reduce the spleen and improve the body condition (many patients regain the weight). This is usually done for few months, and then one crosses over to the transplant (I assume you have the donor identified). Suppression of the blood cell count by ruxolitinib, if it happens (and it may happen in about 25% of patients) is easy to manage since it is dose related; therefore, one would adjust ruxolitinib dose if needed. Good luck with the transplant!

RS: Our current feelings is that patients who are symptomatic with large spleens and who are candidates for a bone marrow transplantation probably should have a course of ruxo before transplantation.  The Myeloproliferative Disease Research Group (MPD-RC is going to conduct such a study to get critical data that does not exist at the present time.  I would favor a trial of JAK2 supporting platelets with prednisone if necessary.  The data would suggest pre-treatment with ruxo may be of advantage.  This has not been shown in a controlled trial, however.  The MPD-RC will be conducting a study of this soon.

RM:The choice of trying ruxolitinib is a personal one.  Clearly, the medicine has demonstrated in myelofibrosis the benefits of improving splenomegaly in symptoms and probably prolonging survival in individuals with advanced myelofibrosis.  As an individual young enough for stem cell transplantation to be a consideration, it is a very delicate discussion of the risks and benefits of each of these options and whether one should pursue directly through transplant or use ruxolitinib prior to transplantation.  So far, there has been limited information about the use of ruxolitinib prior to transplantation and we are awaiting several clinical trials.  You are correct that the use of ruxolitinib may contribute to needing some transfusions pre-transplantation, but whether this potential negative would be offset by the benefit of reduced spleen size and entering transplant in a heartier state are difficult to say.

Timing for packed red cell transfusion in MF?

67. Jan Noble …Can you tell me if there is a “rule of thumb” when considering the appropriate timing for packed red cell transfusion for MF ?

SV: Usual guideline for red blood cell transfusion is to transfuse a patient if hemoglobin is less than 8. However, this needs to take into account a person in question. Older person or a person with heart condition may need transfusion whenever hemoglobin gets lower than 9, for example. Younger person may be fine with hemoglobin levels below 8. What this tells us is that guidelines are what guidelines are for, to follow them but to adjust practice according to a patient’s condition.

RM: As a rule of thumb, we would use in our clinic a hemoglobin of 8 g/dL or, and this is an important or, when the individual is overly symptomatic or short of breath.  So individuals between the range of 8-10 g of hemoglobin may be transfused depending upon how they are feeling.  A transfusion for a hemoglobin of over 10 g/dL would be very unlikely.

RS: There is no rule of thumb for obtaining red blood cell transfusions in PMF.  It depends whether or not a patient is symptomatic and whether or not they have adjusted to a given level of hemoglobin.  In general, patients develop symptoms when they have a hemoglobin of less than 10grams percent.

In general, we do not transfuse patients with a hemoglobin value of 10grms % or more.  Some patients will tolerate a more severe degree of anemia without requiring transfusion because they become adapted to the hemoglobin value.  This depends on the patient’s level of physical activity and other co-morbid condition.  At age 81, I would not be worried about the side effects of p32.  A long forgotten but very important one is that the PVSG showed the quality of life in patients treated with p32 was very good compared to with alternative forms of treatment in the PVSG study i.e. phlebotomy alone or chlorambucil.  Fatigue is a very general symptom, and your physician should give you a complete examination to make sure there are not some co-existent conditions which may be playing a role, for example hypothyroidism which is a very common clinical condition.  If he cannot do this, you should be referred to an internist for a complete physical examination and appropriate testing.

PV & Porphyria,  what about p32 therapy?

68. Mariel Strauss, New Mexico…I have PV and Porphyria.  I have a question about p32.  It worked well for me (could not take chemo in seven tries) and my platelets are near normal now.  But if they go over 800 Dr. Wong at Mayo says to give him a call.  Do you think it is that important to keep my platelets under 800?  I was at 1,500 and did not have a stroke, even though I am 81.  My porphyria makes taking drugs for this impossible (severe side effects including purple toe and low pulse).  I am doing much better after p32.  My feet don’t hurt as much and I took a long walk in the wind tonight in Los Alamos.

SV:  It is very difficult to comment on a management of your particular condition without knowing more details, I am sorry.

In general, patients with ET or PV above age 65 are at increased risk of blood clot due to their age (age is a risk factor, not the platelet number), and the therapy is given to decrease blood counts to normal levels. In patients that have symptoms from the disease (you mention pain in the legs) therapy is indicated to lower the count to normal level, to reduce symptoms. It seems that the doctor is using 800 platelet number as a gauge when to see you and evaluate your condition, rather than a hard number to prescribe therapy.

In general, for patients with ET and PV, one can state that elevated platelet number does not correlate with the risk of thrombosis (blood clot). In other words, having 700, 900, or 1300 platelets makes no difference when we talk about a risk of blood clot. Patients with very high platelets count, more than 1.5 or 2 million, are in fact at increased risk of bleeding; what happens when one has so many platelets is that these platelets consume proteins needed for blood coagulation, and therefore cause artificial increased risk of bleeding.

RS:  At age 81, if Dr. Wong believes that you should have p32, I would not worry about!  Quality of life with p32 is quite good, as was shown years ago by the Polycythemia Vera Study Group. 

The most awful fatigue. Any ideas?

69.  Sandara MatchettI am a 53 year old female diagnosed with ET, slightly enlarged spleen and Jak2+. My current meds are Hydroxyurea 11 x 500 mg caps per week, Aspirin 75mg.My current counts are: Hb 14.7  WBC 7.2 Platelets 482  Neutrophils 5.2

I am not experiencing any other symptoms now that my platelets are reducing, however I am still experiencing the most awful fatigue, which I had before I went on medication 7 months ago.  I work 8.5 hours per day, 4 days a week in an office using a PC.  I do try to keep active by taking the dog for a walk.  I am not good with hills as I get out of breath very quickly, I certainly couldn’t walk and talk going up a hill.  When I get really tired, I get a look on my face as if it is haggard (not great when you are a lady who likes to take care of her appearance).  The fatigue is in danger of ruining my career, social life and any aspirations I had, etc. I am not overweight and I sleep like a baby at night, yet I wake up exhausted.

My question is, ‘Is there any medication I can take to give me more vitality’ I have tried everything else?  Please help?

SV:With excellent control of the blood cell count, one has difficulty connecting a disease and fatigue (i.e. saying that the disease is causing fatigue). Hydrea sometimes can make people more fatigued but you mention that your level of fatigue has been constant all along. One would therefore, look at other causes of the fatigue, as it seems that the disease is well controlled (number wise) and therapy is not causing harm.

RS:  You should have a thorough physical examination to exclude other conditions that may give you fatigue, such as hypothyroidism.  In general, fatigue is not a complication of essential thrombocythemia or hydroxyurea.  Of course, there are many factors that can cause fatigue which are too numerous to be listed here and that is why such co-existing illnesses should be considered.

 Early 30’s with PV…life expectancy?.

70.  FS…  I’m in my early 30’s and have been diagnosed with PV. I am a mild case and only take 81mg aspirin and phlebotomies when required to get my levels in check.

My question is, what should I expect my life expectancy to be? I’ve seen some sites say that with regular treatment I can expect a near normal life span. When I dig deeper I can see that PV can turn to many other diseases/complications if only using phlebotomy for treatment.

My main question is on the life expectancy with phlebotomy/aspirin treatment?

RL:  Most patients without other risk factors (age, history of cardiac disease, chromosomal abnormalities) can do well for a very long time on phlebotomy and aspirin.  You and your doctor need to follow your case closely to ensure things are stable for the first year or two but I would be optimistic that phlebotomy and aspirin will be helpful for a long time.  Some young patients who want to consider treatment with an agent which can put their disease into remisison discuss interferon treatment, which I would suggest you consider given your age, but no urgency to that decision.

RM: It is difficult to know what is the impact of P vera on life expectancy in 2012, particularly for the young individual given new therapies that are being developed such as interferon, JAK2 inhibitors and many others.  As we look in the past, patients with P vera, some but not all individuals have seen their P vera perhaps have an impact on how long they live compared to the normal population.  As an individual younger, it is always possible that a greater amount of time with the disease may make this change more pronounced than an individual who is closer to the end of their life when they are first diagnosed.  That being said, I am very hopeful with all of the advances in science that are being made and new therapies that, although P vera has impacted survival in the past, we are hopeful that we will be able to change that trend for the future.

RS: I do not agree that young patients should be treated with phlebotomy/aspirin only and expect the normal survival.  This relates to the fact that the disease will progress and myelofibrosis splenomegaly will develop usually in the course of 7 to 10 years ( v+).  If your phlebotomy requirement is more than 4 per year, we always start patients on PEG Intron.

The development of polycythemia in patients under the age of 50 occurred in 40% of our database population.  Under the age of 30, it accounts for 15% of our PV patients.  It is not a disease solely confined to the “older age group” and therefore treatment with chemotherapeutic drugs should never be used in younger individuals nor should patients be treated with phlebotomy only.
Jak Neg, looks like PV, could be something else?

71. Meryl Dieterich…My husband was diagnosed with PV back in April 2008.  At the time his CBC was indicative of an MPD so he had a bone marrow biopsy done & the diagnostic note said: “the blood and bone marrow findings are highly suggestive of a chronic myeloproliferative disorder, especially PV.  He is JAK2 negative but his HCT, Hemoglobin and WBC counts all run high.  He’s been treated with phlebotomies only since his dx.  He recently had another bone marrow biopsy which basically said there was no change.  He was tested for the Philadelphia mutations & tested negative for those as well as JAK2 (retested at time of bone marrow biopsy… He seems very asymptomatic except for the fatigue which I attribute to the phlebotomies.  The only other issue he has is that he has these strange lumps & bumps on his hands & forearms.  He was tested for RA & that came back negative as well. Some of these bumps are hard small ones & others are large & squishy.

Since he’s negative for almost all marking of PV, I’m wondering if something else could be going on with him. Any insight you could provide would be appreciated.

SV: Almost all, but not 100%, of patients with PV have JAKV617F mutation, and this is a mutation that doctors test for. About 3% of patients will have different mutation in the JAK2 gene, called “exon 12 JAK2 mutation”. And yet, there are occasional patient for which even this mutation testing is negative. This is why the presence of JAK2 mutation is one of the diagnostic criteria for PV (there are several, of which most but not all must be fulfilled for diagnosis to be made). In the other words, one can fulfill diagnostic criteria and not have JAK2 mutation.

It is difficult to comment on the lumps/bumps; they do not come with PV.

RM: It is true that to make a diagnosis of P vera can sometimes be a complicated situation, particularly in those individuals that do not have the JAK2 v617f mutation.  There are some individuals that will have an alternative mutation that has to be tested for specifically – the JAK2 exon 12 mutation, and there probably will remain even a small subset of individuals who lack either of these two mutations.  The changes in the bone marrow can be an important finding as well as whether or not the serum erythropoietin level is decreased or normal or increased and delineating whether P vera is the diagnosis in an individual who is JAK2 negative is probably best done with the assistance of someone who focuses on MPNs.

RS:  How many phlebotomies is he requiring per year??  Fatigue may be due to the development of iron deficiency which occurs in patients who are treated with phlebotomy only and then become symptomatic from the iron deficiency.  Have other causes of polycythemia been excluded such as high affinity hemoglobin etc?  You do not mention the serum EPO level which is important.
What are do’s and don’t post SCT?

72. Patsy Bushy… Although I have a booklet produced by Be The Match, and my doctor has told me some things, I have found out some things by accident from other SCT patients. For example, you should never clean a litter box for a pet again; you need to wear a medic alert bracelet or necklace at all times, day and night; you should wear long sleeves and slacks when outside and sun tan lotion of #50. I have been told all of these conditions are for life. Would love to have a list of “must do” and “must not do” for protection for the rest of your life, following a SCT.  Cannot find anything but bits and pieces. Had my SCT last April, and I truly am uncomfortable about the fact I have found little about the needs for the rest of my life. I have a wonderful doctor, and he has given a great deal of guidance.

SV: You point out one great need for patients like you and I hope things will improve, and information become more readily available, in near future.

RS:  Those patients with transplant services have all this information available, to them most often in a booklet form.

Does ET progress to Leukemia

73. MJM…We hear many opinions on the progression of ET – does it progress to Leukemia, Fibrosis.  Some say yes, some say no. What is the answer.

RL:  A subset of patients (1-2% per year) can progress to fibrosis or leukemia.  Most patients do not progress but this is an important reason for close follow-up.

JM: Essential thrombocythemia can progress to myelofibrosis at a rate of 10-20% over the first 10 years from diagnosis and less frequently (3%) to acute leukemia.  Many patients with ET do not ever progress to MF or acute leukemia and in fact the median survival of ET patients is essentially the same as a sex and age matched cohort

RS:  The true form of ET progressing to leukemia occurs very rarely.  Many patients treated with ET may be with one or more types of chemotherapy which may play a role in the development of acute leukemia.  We see this especially in patients with primary myelofibrosis who have been treated with a variety of chemotherapeutic agents especially hydroxyurea.  This has been known for years and was reported by Ellis J et al for the PVSG.

 RM:  Patients with ET may progress to acute leukemia or to post-ET myelofibrosis.  That being said, the rate of change to these things is probably lower in ET than in those with P vera.  The confusion arises that there is a current discussion that those who have been historically diagnosed with ET, some have a form of ET that is fairly benign and has a low likelihood of progression and others have early myelofibrosis.  It takes quite a specialized hematopathologist to help distinguish these two groups as well as a clinician.

Need Joint replacement but does MF make it pointless?

74. Terry RoncinI am a 53yr old female, primary MF. I need joint replacement in both knees and right shoulder which has given me a severe rotary cuff tear.  Is it worthwhile to try and be placed on a year’s waiting list here in Canada for joint replacement.  Or does the MF affect the bones and cartilage connecting to my joints which would in turn affect the outcome of the surgeries.

SV: One would of course like to know much more about your MF to make more informed comment. However, in general, having MF does not preclude my patients from having surgeries of this type. Quality of life is very important and I have no doubt that joint replacement has a great potential to improve your quality of life.
RM- As a relatively young individual with primary myelofibrosis, in general, we would not feel that the diagnosis of myelofibrosis would preclude you from either benefiting from a joint replacement nor make such a surgery not an option.  Clearly, this needs to be an individualized choice discussing both with your hematologist and orthopedic surgeon, but at least in my practice, would probably not preclude an individual from considering this surgery.

RS:  Does your orthopedic know you have PM?  Long bone (femur) can certainly be affected.

Treatment options for 80 year old Mom with PV

75. Mary Williams…  My 80 y/o mother was just recently dx’ed with polycythemia vera on 8/6/12.   She had a platelet count of 833 K, WBC of 11.6 K, RDW of 16.7 %.  Her Hgb was 12.8, Hct 39.2.  Her B12, iron were OK, erythpoeitin was low.  JAK 2 mutation was +.  She was placed on Hydroxyurea  500 mg twice a day.  First couple of days she had some slight nausea, diarrhea.  After one week, she experienced an itchy rash on her neck and upper chest.  She called her hematologist and she stopped the Hydrea but the next day, my mom developed swelling of her lower lip…

My mom always seems to get whatever side effects of a medication that there is.  I am concerned about what I read as the options for intolerance of hydroxyurea for her MPN.  I am thinking with this new development of not tolerating the recommended treatment for her condition, that maybe we should get a 2nd opinion from a center that deals with MPN’s on a regular basis

She was having no symptoms from the high platelet count prior to this. She really does not look like the signs of polycythemia vera that the literature describes.  I am afraid that the treatment options will just make her sick feeling and what kind of life is that.  Recommendations?

SV: In general, patients with PV above age 65 are at increased risk of blood clot due to their age (age is a risk factor), and the therapy is given to decrease blood counts to normal levels. It is not as much about having a symptom from the disease, which many patients do not, to start therapy but about the risk of having significant impairment of quality of life due to a possible blood clot (e.g. stroke). Hydrea is the first, standard, therapy for patient with PV and I hope that a lower dose (e.g. once day) might be tried to see whether your mother can tolerate it. There are other possible therapies, including some investigational therapies, for patients not tolerating hydrea. If there is any doubt about diagnosis or therapy, second opinion is good option.

RS:  According to the criteria I use for the diagnosis of PV, your mother does not have it.  It sounds more like essential thrombocythemia but not all data have been submitted.  A bone marrow could be helpful.  In any case, starting at a dose of 1,000mgs of hydrea a day in an 80 year old woman with displayed counts you reported is high in my experience.

Husband just dx w/MF, what to do?

76. Katie H…My husband was found to have Stage 3 of 3 Myelofibrosis  3 years and 5 months ago.  We initially were on Hydrea 500mg for various days over approximately 18 months and my dear Ivan seemed to be doing well, living normally, his only complaint was joint and bone pain, not taking a thing.  Then about 5 months ago and especially the last month, his conditions seems to be getting worst everyday. He has lost so much weight that actually I know for the first time what skin and bones mean.  He does not sleep and has no appetite, even his favourites he takes a few bites and is full… We found out that his spleen is enlarged and he seems to have pain where his liver is. Our GP says jaundice is now a problem….

Our specialist is Dr. Terry Frost, of Brisbane. My husband is now taking Hydrea 500mg 3 times a week for the last 6 weeks.  We are on various puffers for his coughing. I feel there must be something else we can do….Dr. Frost has mentioned trials but nothing has come of it….. We see  Dr. Frost on this Thursday…..What do we ask him?…..I am worried I am losing my Ivan, he seems to be getting worse every day and I have no idea how I can help him..

SV: Myelofibrosis is unfortunately progressive disease and I am sorry to hear about your husband’s condition deteriorating. Without knowing the details, in general, one would suggest searching for clinical trials in Australia with new medications, JAK2 inhibitors, that may help with many of the symptoms as well as with enlarged organs (they improve both). Ruxolitinib is a JAK inhibitor recently approved in the USA, Canada and Europe, perhaps it is/will be available in Australia.

RS: We are so sorry to hear that Ivan is doing badly.  The development of jaundice is not a good sign unfortunately.  It would be important to know if this condition has changed into a leukemic phase and so you should tell us what his bone marrow and peripheral blood showed.  Perhaps prednisone would be of help

Peg dosage and can it stop MF?

77. Jeremy…I am fifty-three years old and had PV for twenty plus years and was taking Hydrea for all of those years. I have recently converted to mylefibrosis. I am no longer on hydrea and my Doctor increased my aspirin to 81MG Low dose four times a day from one and stopped my Hydrea.  My Doctor has recommended PEG- treatment 45mg once a week for two weeks to start.  My question is am I starting on the right dosage of Peg-INFN and has PEG-INFN in clinical studies shown the ability to stop myelofibrosis or just PV?

RM: At this point in time, the data does seem to suggest, in P vera in particular, that the use of interferon may help delay progression to myelofibrosis.  There have been also individuals with early primary myelofibrosis, i.e. myelofibrosis with less than the most advanced grades of fibrosis and massive splenomegaly that have seemed to have some bone marrow regression to fibrosis in particular with use of the medicine.  Ongoing studies are looking at how much we can count or what is the likelihood of having this benefit with the use of interferon.

 RS: We like to start with low doses and gradually increase is tolerated.  PEG interferon can be very helpful in this kind of myelofibrosis presuming that the bone marrow shows residual hematopoietic (blood cell function).

SV: This is good plan and the dose is right. Therapy may positively affect the bone marrow and halt progression of the disease. Although there are no comparative studies done to prove that interferon therapy can stop progression of the fibrosis, and in some cases reverse it, there is enough published literature to suggest that this is indeed possible (particularly from work by Dr. Silver in NYC).

Peg studies hi-risk, any lo risk studies

78. Michael M… It appears to me that most studies done with Pegasys are on patients who are high risk. What studies, if any, have been done on Pegasys with low risk patients? If there are none, what results have you seen to date?

SV: Pegasys was studied in patients with PV, both newly diagnosed and in those with more advanced disease, and it was very effective in both in controlling blood cell count (85-95%). It was also used in patients with myelofibrosis, where it was more effective in those patients with proliferative disease than in more advanced disease, like the experience with regular interferon in the past.

RM: Up to this point in time, there is limited information on the use of pegylated interferon and individuals with low-risk P vera.  That being said, some of the benefits that we hope for in P vera [of helping delay] progression.  Maybe this is relevant with low-risk individuals.  The risk scores with polycythemia vera primarily relate to risk of blood clot or bleeding events and do not relate to the risk of progression.

RS:  Low risk patients with myelofibrosis have been treated by me and my group with interferon. [It] affects megakaryocytes and presumably its breakdown products and decreases the development of fibrosis  We believe that the treatment should be earlier than later.  Other investigators such as Hasselbalch in Denmark and Kalidjian in France also agree and published on this very same subject.  Our paper appeared in Blood June 2011.  It showed that 80% of patients with prefibrotic or intermediate one disease will benefit as manifested by improvement in blood count,  decrease in spleen size, bone marrow reversion, etc.  Of course this was a phase 2 single arm study and this data must be interpreted in that light, however, the results are most encouraging.

70 y.o. doing great on Jakai, what about a cure?

79.  Susan Hill… I am a Myelofibrosis patient who was diagnosed in 2001 at age 60 and was told this was a “ten year disease.”  I’m happy to report that Jakafi came along just in time as I was seriously ill in 2008-2010.  I participated in the Comfort I Study and was fortunate enough to receive the actual drug.  The rest is history!  Today I am an energetic, healthy grandma with a future to see my granddaughters grow up.  Other than my monthly blood transfusions, I am as normal as any other 70 year old!

My question concerns the current research efforts.  Having attended the last two MPN Patient Symposia in California, I am encouraged by the reports we heard from the researchers.   What is the current status of research toward a cure?

JM: There is a significant laboratory research effort to better understand the biological mechanisms that drive myelfibrosis. As we advance our understanding of the different gene mutations (genetic lesions) and associated protein abnormalities (epigenetic lesions) that work in concert to cause hematopoietic stem cells to transform into clonal MF cells, we can better target these cells and eliminate them. Currently, stem cell transplantation is the only therapeutic option that offers the potential for cure at a risk of transplant related mortality that is not insignificant.  The approach to transplant is being refined and improved and transplant outcomes are continuing to improve. We do not have medications that reverse the bone marrow abnormalities that characterize this disease and extend life expectancy (disease course modifying agents). Future trials will combine current experimental therapies that have shown signals of activity as monotherapy in myelofibrosis (e.g. JAK2 inhibitors, histone deacetylase inhibitors and immunomdulatory agents) with the hope that these combination therapy approaches will better target and remove the malignant bone marrow cells sparing normal bone marrow cells.

SV: Development of JAK inhibitors as therapy for myelofibrosis is the first building block toward finding a cure. I am very happy to hear about your excellent response. Ruxolitinib improves signs and symptoms of the disease and it seems that with that it can actually prolong life of patients with advanced myelofibrosis. It does not eliminate bone marrow fibrosis, or the malignant cells from bone marrow or blood. Efforts are underway to combine with JAK inhibitors other targeted medications, either commercial or investigational, to improve the response, perhaps to improve bone marrow fibrosis, improve blood cell count, and further extend the good quality life. This is more realistic next step, but an important step toward finding a cure

 RL:  No long-term remission and/or cure.  Please keep coming to the meetings as we keep working towards that goal. No current treatment is curative, but we are all working to identify better therapies, including combination treatments, which might allow us to work towards that goal,

RM: At this point in time, we view that ruxolitinib and other JAK2 inhibitors are giving a significant benefit to those with the disease.  We do not feel that it is a cure.  Combination studies are ongoing to see if we can greater impact the disease.  Clearly our goal is moving in the future towards a cure of the disease, but we do not yet have a medical therapy that we can say, outside that of stem cell transplantation, we could accurately call a cure.

RS: How wonderful that you feel so well, Susan!  This is great news and it encourages all of us working in the field.  We are all trying to work towards a cure.

4 yr old son, high platelets, confused dx, BMB?

80. Holly Swanson…My 4 year old son has been a fairly healthy child up until last October when he suddenly came down with acute pneumonia. Then in December he had labs drawn for the first time after he had been complaining his feet and hands hurt. He has since had persistent thrombocytosis for 10 months highest was 684,000 back in and lowest he has ever been was 487,000 (<that was a recollect draw because lab error) he has had over 6 CBC w/ differential w/platelet tests and all 6 times come back looking the same; elevated platelets slightly elevated: hematocrit, hemoglobin, RDW, eosinophils and at times monocytes….He has since had rashes all over his body that come and go for no apparent reason; his former pediatrician said he has never seen “eczema” this involved on the body but since it itches he is going to diagnose it as eczema. He had been complaining that his hands and feet hurt and they feel “funny” (that was when his platelets were in the 600,000 + range) and he will still complain about them hurting but not as often now. He has seen an hematologist at Loma Linda Childrens Hospital 2 times back in January (5min visit each) who said “he prob has a virus his platelets will come back down within normal range soon” “reactive thrombocytosis”; he sent my son back to his pediatrician for follow up with his care who has retested him 2 more times and its still elevated and doesn’t know why it’s like that and said there is nothing he can do.  No more testing is needed. … His new Pediatrician agreed and said maybe he has the Essential Thrombocytosis a Myeloproliferative Disorder… His new pediatrician said in the 37 years he’s been practicing medicine, he as never been so puzzled by one of his patients labs because even though he has thrombocytosis and other labs are only slightly elevated, they are not in any critical value ranges and all the other organ functioning tests come back completely normal. My questions are what are these doctors missing if anything? Is the next appropriate step a Bone Marrow Biopsy?

SV: I am very sorry to hear about your son’s condition and hope that involved doctors will find the answer soon. The bone marrow biopsy is reasonable next step; I do not see anything obvious that has not been done so far. Hope the answers will be coming soon from further testing, but sometimes we find no answers. 

RM: MPNs are possible in children, but there are many potential confounders and other congenital situations that can mimic MPNs in children, particularly those very young such as a 4-year-old.  I think having expert second opinions in pediatric hematology specifically would be very important to be sure that the diagnosis is both accurate and to determine the therapy.  Almost all the information that you will read in MPN clinics or on the [list serves] are really specific to adults and the use of medicines, which medicines and what are their goals will be a different discussion with children that needs to be very individualized as there is unfortunately very little information on optimal treatment of these patients if they are pediatric in age.

RS: Absolutely see a pediatric hematologist.

PreMF diagnosis, is MF inevitable?

81. Amy… Is there a difference between bone marrow scarring from ET vs MF.  My doctor indicates I have scarring of the bone marrow but has stuck with ET dx. My BMB states the following: Final Diagnosis: Chronic myleoproliferative neoplasm with mild myleofibrosis. Diagnostic Comments: The differential includes the pre-fibrotic stage of primary myleofibrosis and essential thrombocythemia.  It is difficult to differentiate between these entities at this stage as approximately 15% of PMF cases present with thrombocytosis and a minority of ET cases present with mild reticulin fibrosis …. Followed up with CAT Scan of pelvis and abdomen which came back fine.  JAK2 positive, Platelets usually 1.25 -1.32 million…  Dr. says it just means I have a pre-cursor to PMF, is pre-cursor same as inevitable

SV: Presence of bone marrow fibrosis in the bone marrow does not automatically means that one has disease Myelofibrosis. Some fibrosis can be seen in patients with ET and PV, as well as in some other bone marrow diseases. For each entity, ET, PV, and MF, there are diagnostic criteria that need to be fulfilled and I would suspect that your doctor is following them.

RM: The rate of progression for individuals with ET, even with mild fibrosis, can be quite variable and in some individuals it could take potentially many years before they would progress to overt myelofibrosis.  It is possible that new therapies may impact this rate of progression, but I would not say that it is inevitable that progression will occur.  Many factors remain.  Given your youth at the age of 46, we would tend to think that the likelihood of progressing at some point in your life is possible, but surely that might be impacted by therapies being developed.

RS:Amy raises a very important point.  Fibrosis (reticulin fibrosis) is seen in 5% of patients with ET.  This does not mean you have the disease entity “primary myelofibrosis”.  It also does not imply “scaring of the bone marrow” nor does it have the same implication.  However, an experienced hematopathologist should be able to distinguish the pre-fibrotic stage of primary myelofibrosis and true essential thrombocytosis.  We do it in more than 85% of cases.

 Omega 3 better than Aspirin?

82 . Susan Kennedy… I am taking aspirin 81mg daily for PV blood thinning.  I have recently read (Journal of the National Cancer Institute) that daily aspirin increases risks for breast and pancreatic cancer.  Also, The American Journal of Preventative Medicine states that omega 3’s naturally thin blood and are more effective without the risks of aspirin. Does anyone know anything else about this?  Do some MPN patients take omega 3’s instead of aspirin? 

SV: In PV it has been shown that taking aspirin is beneficial for patients and has therefore become standard practice to prescribe it. I am not aware of any studies in PV with omega3.

RS: Dear Susan, please do not refer to “blood thinning”.  Aspirin is used for preventing coagulation because of its effect on platelets.  It prevents them from clumping.  It does not “thin” the blood.  I am not familiar with a decrease in pancreatic cancer and such study should be read very carefully; the study you have reported, I have not read as yet.

 MF, why are some hem’s against Ruxo?

83. Tiziano Giunti… I am afflicted with myelofibrosis post PV I am using Ruxolitinib for two weeks, my spleen has already reduced and I feel much less tired than before. My hemoglobin is 14 and platelets 190 thousands (before beginning 110 thousands).I would like to know why some hematologists aren’t in favour of Ruxolitinib/Jakafi, that remains the first and only JAK2 inhibitor at our disposal.

SV: Good question but no good answer to it. Ruxolitinib is good in improving quality of life in patients with MF, and it is very good in reducing enlarged splee and liver in MF. Therefore, it is not for every patient. In those needing help, it should be tried. If it lowers significantly the blood count, the dose needs to be adjusted, otherwise in general there are no other common side effects

RM:  Ruxolitinib is a very helpful medicine in that it has impacted splenomegaly symptoms and potentially how long an individual lives with more advanced myelofibrosis.  It has been particularly helpful in those with PV myelofibrosis as these individuals tend to have less issues with anemia or low platelets with this medication.  I think it is not a question of whether someone is for or against ruxolitinib, I think it is important to have a realistic expectation of the benefits one might have with this medication and how to monitor it accordingly.  The medication is not a cure for myelofibrosis, but does seem to benefit many of the individuals who have received it.  What the level would be in earlier disease is something that still remains experimental.

RS: It is best to ask those hematologists who are not in favor of ruxolitinib.

 Compare benefits Peg and Jakafi

84. Dave Mueller…I am 52 and was diagnosed with early PMF in 1/11.  I was a bit anemic and had a large spleen of 9cm.  I began Pegasys a few months later at the suggestion of RS, and ramped up my dose to 90mcg before beginning a trial for SR Jakafi.  My spleen was measured at 15cm at this time and my decision to try Jakafi was based on my enlarging spleen.  I am now currently on 20mg Jakafi and 90mcg Pegasys.  I think I’m doing well, but other than feeling good on this combination, is there any way to tell if I am benefiting from it?

I have tracked my counts back a year before diagnosis, and they have been pretty much stable up until starting Jakafi which lowered my platelets and hgb.  My platelets are now stable at around 113k and hgb is back up to pre jakafi days at 12.2.  Most people I speak with see a lowering of counts while on Pegasys, and I can’t tell it’s made any difference.  No change the 4 months on Pegasys alone before starting Jakafi.

I know a bmb may provide some answers, but I want to wait a bit longer.  The benefits I see from Jakafi are reduction in spleen (now at 7cm) and reduction in night sweats.  What I see from Pegasys is reduction of bone and joint pain and an increase in energy.

So has this combination helped keep me stable, or would I have been stable without it?  I think my spleen would be a whole lot bigger now.  Latest CBC wbc 5.9 rbc 4.06 hgb 12.2 hct 35.5 rdw 17.6  plt 113.

RM:  At this point in time, the benefits of these two approaches are different and there is a potential that there may be some synergy to be explored in the future.  Pegasys potentially can help the control counts, help to improve symptoms sometimes and may have an impact on delaying progression of the advanced disease.  Ruxolitinib has been tried in people with more advanced disease and has helped splenomegaly symptoms and potentially survival.  The goals are slightly different with the use of these medications and needs to be discussed with your hematologist, as I would have a different expectation on timelines of benefit for both of these medicines.  As I mentioned, there will be efforts to see what a combination approach with both medicines will do in terms of helping individuals.

RS: Dear Dave: the combination of pegasys and jakafi is a very intriguing one.  A study is beginning in Europe with this combination.  It is very hard to tell how much you are benefitting from the combination without assessing the bone marrow but in general, responses to interferon in PMF take at least 6 months to a year so I won’t rush into getting another bone marrow.  The dosage seems about right.  As long as your spleen is getting smaller and or stable and you are feeling much better, I would stay on this current course

 ET with good numbers, premature for BMB?

85. Elizabeth Goldstein…   I have ET, diagnosed almost two years ago.  Right now, my blood work looks good but if my bone marrow becomes fibrotic, how long will it take to show up in myblood work?  Am I being over cautious to ask my hematologist for a bone marrow biopsy every two years (assuming blood work is still good)?  She is a good doctor and has agreed to do this but am still wondering if I’m just worrying too much.

SV: In patients with ET bone marrow biopsy is usually done as needed. This means that it is done if/when blood count shows significant change, e.g. anemia, low platelets, abnormal types of white cells, or similar. How long, and if at all, these changes will happen we do not have a way of predicting. We do not suggest bone marrow biopsy just to check whether there is any change. A presence of some fibrosis in the bone marrow does not mean that the disease has changed to Myelofibrosis; there are other factors, like those I mentioned one can see in the blood, that make up a criteria that needs to be fulfilled for Myelofibrosis to be called.

RM: A bone marrow biopsy is very helpful as a baseline in people with ET and P vera to see if there is any fibrosis, any increase in blasts, any changes in chromosomes.  If an individual is stable, the bone marrow would only need to be repeated if there was evidence of change in the disease in terms of blood counts or how the individual was feeling, but a baseline is very helpful so that if an individual does progress, we know where they started from.

RS: Dear Elizabeth, you did not tell us what your bone marrow showed initially.  If it was consistent with essential thrombocythemia, and if your blood work “looks good”, you may not need a bone marrow at this time.

PMF. Jak 2 Neg and MPL pos… what does it mean

86. Jack Pelfrey… was dx with PMF in 1998, I go to Stanford for blood draws, I feel good do not take meds.  I was told I have the MPL mutation.  I do not have the JAK2 mutation.  What does having the mutation mean to me?

SV: There is no particular clinical relevance whether a patient has JAK2 mutation, MPL mutation or no mutation.

RM:  MPL is a mutation that can function very much like mutations like JAK2.  We do not feel that there is a significant difference in how the disease behaves.  Individuals with MPL mutations will tend to respond to JAK2 inhibitors just like those who have the JAK2 v617f mutation.

RS: You have excellent hematologists in Stanford who should address this question.

ET…burning, skin sensitivity.  HU?                                                                                                                     

87. Amy Rubin ET, burning pain, back and hands.

I am a female age 60 living in SeattleWa. I was diagnosed with Essential Thrombocytosis at the age of 59 through blood work; I have a Jak 2 mutation.The  hematologists I have consulted see no need for a bone marrow biopsy.

My platelet count has been between 570-650 for the last 18 months; my counts have exceeded the normal range since 2008 but have never been over 650. Dr. Harlan is my current hematologist. For the past fifteen months I have had burning in my hands and arms which occasionally goes into my legs and back. The touch of any fabric on my inner arm or wrist will trigger even more pain so I can only be reasonably comfortable when dressed in a t-shirt and shorts.

I have had all sorts of medical tests including a complete neurological workup which showed nothing… The hematologists I have consulted think that there is only a 10% chance that the Essential Thrombocytosis is causing this pain. I am afraid to take hydroxyurea because of its potential side effects and possible connection to cancer, so am only taking a baby aspirin. Has anyone else with ET reported symptoms similar to mine? Would you advise me to try a trial of hydroxyurea to see if my symptoms abate?

SV: Symptoms from ET include those symptoms you have described, yes. If the extensive work up, you mentioned, has      not revealed any other possibility to explain the symptoms, it is reasonable to assume it is due to ET. The real answer will come, you are correct, from trying hydrea. After a couple of months the symptoms should go away. Alternatively, one may try different medications that are used for neurological conditions, for example, Paxil, Elavil, Neurontin or similar. Occasionally they may work as well

RS: All patients with a myeloproliferative disease should have a bone marrow done at diagnosis.  Of course not only to aid a proper diagnosis but establish a baseline for development of future fibrotic changes (see question 85).  I certainly will not give hydroxyurea without defining the issues as much as possible and in this regard a bone marrow biopsy would be of help.  You also did not say what your hematocrit or white blood cell count were.

Connection between Low cholesterol and MPNs

88. Matthew Hicks…I am 49yo male diagnosed with PV in august 2010, almost a year after a MI. Under care of experienced haematologist. Main symptoms at time of dx were arthritic type joint pain in wrists, knees, shoulders and aquagenic pruritis. All blood counts were elevated. Have had 3 BMBs. First showed reticulin fibrosis MF-2 but later ones show had lessened. Initially had 8 venesections. On INF – Intron A – (Pegasys not available for MPNs in Australia). Ferritin iron readings had been very low till early this year but increased significantly in 2 months. Will be checked for haemochromatosis next CBC. My question though relates to cholesterol readings. Mine have always been low and at time of dx I was 2.4 total chol (range 3.5-5.5 here in Australia) which I think is about 100? in US range ie very low. Currently 2.6 total chol. I know of some literature on connection between low chol and MPNs (Harriet Gilbert I think) and thought had read somewhere of possible unfavourable prognosis with very low chol in MPNs. Any comment on any significance of very low cholesterol?

RM: We have identified in the past that MPNs, perhaps through making the spleen more active, may help to decrease cholesterol by the spleen chewing up some of the cholesterol in the bloodstream.  It tends to lower the good and bad cholesterol, LDL, and HDL.  We do not know, in fact there is no proof, that the lowering of cholesterol by the illness is beneficial in terms of protecting from heart disease.

RS: You are right.  Harriett Gilbert was the first to note the low cholesterol values and myeloproliferative neoplasms.  She attributed this to patients who had large spleens.  Patients with PV of course have low serum irons as you did since you had phlebotomies.  Serum iron will rise in response to the use of interferon.  That is a characteristic, it does not suggest hemochromatosis at all.  You might check on your cholesterol values as your polycythemia continues to respond to interferon.  It should rise.

 Pegasys, menopause and skin issues…continue Peg?

89. Susan Ketcham…  I started Pegasys on July 28th at a dose of 90 mcg which I am still on.  My WBC is under control after rising to the low 20′, but unfortunately my platelets have been rising, presently at 745 (I stopped HU 3 weeks ago) so my doctor wants to raise my dose to 135 mcg. So far my HCT and HGB are holding at around 42 and 13 respectively.
I have had the usual side effects (mood swings, achy joints, headaches, fatigue, dizziness) which are far from fun but which I can tolerate, however I am worried about a few things.  Since I began treatment my AST which averaged 35 prior to treatment, has risen to 65, which is above normal.  My ALT, which averaged 16, has risen to 43 – still normal but just.  In addition my LD has gone from around 560 to an above normal 675.  All of my other liver enzymes remain pretty steady, but my liver, already compromised by a portal vein clot and Nodular Regenerating Hyperplasia, is obviously taking a beating from the Pegasys.
In addition, at the same time I started the Pegasys I also seemed to have started menopause with a vengeance! …. AND, finally, I am having a weird skin problem where I have little red bumps randomly appear on my arms, trunk and crotch area, that itch briefly then scab over.  …Continue Pegasys?
(Background) Other medications – Warfarin, Omeprazole, Nadolol, Cymbalta, Aspirin 81mg, Sonata PV diagnosed in 2006, but present since at least 2000, sMF diagnosed in 2010.  HU therapy for six years with fluctuating counts… Platelets that WILDLY fluctuate as much as 400 points in a ONE WEEK PERIOD. Have gone from 31 to over 1,000,000 in a ten day period – both labs repeated, both labs done at UCLA.

SV: As with any other therapy one should balance the risks and benefits of Pegasys. The best strategy in long-term therapy like this one is to engage closely with treating physician and work things out as a team. I would suggest talking to your doctor about your concerns, and listening/understanding his view on the matter. Only then the proper plan can be put in place. For example, since you mention multiple side effect (although tolerable) one may want to wait some time to see whether they will go away as the body adjust to the therapy, or will get worse on the present dose. In general, with chronic therapies there is no rush in changing the dose/schedule and one needs to be sensitive to side effects, for therapy to be given long-term and produce desired results.  

RS:  I would first check the laboratory for your platelet counts.  This cannot be due to the disease or medication.  Of course UCLA is an excellent institution.  Perhaps your blood was not done in the same lab or by a different technician or SAT before being submitted, etc.                                                                                                                         

 Two kids with mastocytomas. Need BMB for dx, risk for MPN

90.  Bonnie Nasar Two of my four children have solitary mastocyomas. We have not had bone marrow biopsies, so I do not know if it is systemic or not. My question is, what are the odds that I have 2 kids with solitary mastocyomas in the same place on their bodies and this is not considered a genetic disease? Also, is there or will there be any way to find out if it is systemic without a bone marrow biopsy? Also ( I guess I have more than one question) one of my kids showed a significantly elevated risk for developing an MPN but the other showed normal risk. Both kids are diagnosed. What does that mean?

RS: I think a geneticist would have to comment on the risk of developing a MPN in this case.

SV: Mastocytomas happen in the kids and are considered benign condition. However, depends where in the body they are, they may interfere with the function of affected organ/body part and may need to be removed. It is unusual to have two kids with it.

Systemic disease can only be diagnosed by the bone marrow biopsy. If body organ function is not affected (normal blood count, liver function, etc) then there is no need to do bone marrow biopsy. There are 2 types of systemic mastocytosis: indolent type which is present in the bone marrow but does not affect organ function (indolent in its name indicated its benign nature), and aggressive type that does affect organ function. The one that matters is aggressive type which would already be evident if blood count is abnormal, liver function abnormal, etc, as mentioned.


 Have ET…Any link between aspirin and boils

92. Jackie Donegan …   I have probable ET jak 2 negative current platelets 705 on aspirin and have recurrent boils. Is there a link?

RS: No connection between the boils and essential thrombocythemia that I am aware of.  Likewise aspirin.

SV: I don’t know of a link between aspirin and boils.

RM: Difficult to say.  There are people who have aspirin allergies.  Typically would manifest more as hives than as boils.  ET certainly can cause itching.  It certainly can cause redness in the skin called erythromelalgia, but typically not boils.  I would work with your dermatologist to look for potentially alternative causes.

 PV dx 09,converted to MF. Is Peg a good option?

93. Augusto Filho..My name is Augusto Ornelas Filho, 48 years old, and I am from Brasília, Brazil.

I was diagnosed with PV (JAK2 V617F positive) in 2005. Before treatment, I had portal vein thrombosis, inferior cava vein thrombosis (partial) and a renal vein thrombosis. It was all asymptomatic, detected during image exams….I have been taking hydroxyurea (1.000 mg/d), warfarin (7.5 mg/d), aspirin (81 mg/d) and omeprazole (20 mg/d).

I have had very good quality of life: asymptomatic disease, blood counts under control (hematocrit <= 45%; hemoglobin around 14.5 g/dL; platelets around 280.000 /µL; and leucocytes around 6.000 /µL); little splenomegaly; few phlebotomies during this period (2 or 3 each year); and no additional thrombotic event. Suddenly, I had my blood counts reduced, checked in my routine blood test of August, 2012. My hemoglobin dropped to 12.0 g/dL, my platelets to 160.000 /µL and my leucocytes to 5.000 /µL. At that time I could feel some fatigue and I started to have, sometimes, very low fever (37 °C) and night sweats.

I had a BMB September, 2012 and we could see that my disease transformed from PV to PPV MF. Now I have myelofibrosis.  The karyotype is normal, but the bone marrow fibrosis grade is MF-3

As far as I can understand, hydroxyurea is not a good option for me right now because it has no effect on the fibrosis. Maybe, Pegasys could help me with the stabilization of the bone marrow fibrosis or even with some reversion effects on it. I have read that Pegasys would be better for early MF but I don’t see any other better option for me. Even with the MF-3 grade, my bone marrow is hypercellular (95%), my CBC counts are still fine and the only constitutional symptoms that I have had are unexplained low fever and night sweats, sometimes, during the last month…Considering that splenomegaly is not my main concern right now (spleen of 19 cm, palpable at 4 or 5 cm below the left costal margin), do you think Pegasys would be a good choice for me? I didn’t have any problem with hydroxyurea but, as far as I know, it doesn’t help with the fibrosis reduction?  I imagine this is the best option for me now! I am feeling good anyway, but very worried about what direction I should take!

RM: Pegylated interferon may have a benefit for individuals with early myelofibrosis.  Clearly it is difficult to advise what would be your optimal therapy based strictly on your question, but given your youth and your time with myelofibrosis, certainly it would be a consideration that would be potentially helpful in trying to delay further progression of the disease.

SV: I think that Pegasys is very good choice for reason you have mentioned. I am very happy to see how well informed you are about your disease and therapies.

RS: Many patients with portal vein thrombosis have a “forme fruste” (hidden) of polycythemia vera.  The reason they do not have an elevated hematocrit is because the plasma volume is increased and thus a “falsely low” value for hematocrit is found.  That is a the importance of a red blood cell 51 chromium mass study which in these cases virtually always demonstrates an increased red blood cell volume which has been masked.  Hydroxyurea will not prevent the further progress of fibrosis in the bone marrow.  You have read earlier questions, patients responding to interferon.  This is the drug of choice for you in my opinion.

ET at age 39, brain aneurysm, ET related?

94. Sandra Birdsall… Was dx with ET back in 1994 at age 39 and have taken hydroxyurea ever since, with a 500 mg daily dosage effective all this time in keeping platelets in the 450 range.  3-1/2 years ago I suffered a nearly fatal brain aneurysmal hemorrhage and subsequent stroke.  I have always wondered if the ET contributed to this event–I have tested JAK2 positive.  It has been a very long road to recovery.  Any comments?

RM: In an individual with an MPN who had a stroke at an early age, we would have to be highly suspicious that the MPN could be a contributor.  There is no guarantee that the MPN is the cause as you mentioned a bleed from an aneurysm that could have been an anatomic event.  That being said, we would have to be very cautious that it could be the ET and aggressively control counts accordingly.

RS: Very hard to say.  If it were a true aneurysm and if your platelet count was very high at the time, it could have contributed in part to bleeding.

PV controlled w/PEG, need equivalet INF

95. Richard Albert… I have been turned down for PEGASYS after having used it successfully for 2 years. I have PCV for 23 years now all counts presently well controlled. I would like to continue with some kind of INTERFERON as I believe it is presently the only drug that can arrest the prgression of the disease I was taking 135ug PEGASYS What would the equivalent dose of Inteferon be? Is anyone looking at combo therapies of Interferon AND HU? When INTERFERON was the old Standard Remedy many years ago,for those who could tolerate it what was the conversion rate to AML and Myelofibrosis like.

RM: It is difficult to translate the dose of pegylated interferon and regular interferon, but similar ranges of Pegasys which would be about 90 mcg a week would typically be similar to about a million units of regular interferon three times a week.  Individuals with regular interferon typically will need between 1-3 million units three times a week whereas as you’ve seen people with Pegasys will typically need anywhere from 45 to as high as 180 mcg per week.  The goals of this therapy are twofold.  1) To try to control counts; 2) to try to delay progression.  Delaying progression may need lower levels of the medicine than the level needed to control the counts.  There are times that individuals that need higher doses of the Pegasys or regular interferon to control counts, we will consider combination therapy.

RS:  You have asked a recurring question.  There is no qualitative difference that I can find between the different types of interferon.  Only convenience and perhaps decreased side effects with PEG.  Therefore, it is perfectly safe for you to take interferon alpha 2b.  There is no exact equivalent dose of interferon.  You can start at 2m units 3 times a week that is roughly equivalent to the 135mu of Pegasys.  Interferon is not an “old standard remedy.”. We use it all the time.  We do have patients whose insurance company does not pay for PEG for reasons I do not understand.  There is no evidence that interferon of any type predisposes to the development of AML or myelofibrosis


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Comments on: "MPNclinic…November 15, 2012" (8)

  1. Having been told I am jak2 neg and secondary polycythemia as a diagnosis ,Iam now being told I’ve got true polycythemia.My hct 0.514 ,hb 16.7,white cell count 10.19,platelets 363 Iam being venousected every 6weeks but feel no benifit as Iam still fatigue and blood letting makes me feel shocking ,I have normal sleep studies ,normal erythropoietin,normal p50 oxygen dissociation curve,normal chest X-ray, red cell mass consistent with true polycythemia ???your forum has told me more than my own hospital which now tell me I’ve been put down to see a professor Porter at uch London can any one please help a very worried 43 year father with some advice as I feel very alone and to look at my children is breaking me mentally as I feel helpless. David

  2. Fantastic to read the different views of the well regarded experts. I found it fascinating and learned so much on this type of forum. Thank you to the Doctors for answering the questions so a lay person can understand. bonnie Evans

  3. ALSO, most importantly, THANK YOU TO EACH PERSON involved in putting MPNclinic forth! There are so many little bits of info to be gleaned from each post that may be helpful to each of us, so we should read every one carefully. It’s amazing how much valuable information I’ve gained even when I didn’t thing a topic pertained to me.

  4. RE ABOVE: He seems very asymptomatic except for the fatigue which I attribute to the phlebotomies. The only other issue he has is that he has these strange lumps & bumps on his hands & forearms. He was tested for RA & that came back negative as well. Some of these bumps are hard small ones & others are large & squishy.

    Since he’s negative for almost all marking of PV, I’m wondering if something else could be going on with him. Any insight you could provide would be appreciated.

    My Comment/question: I have the lumps and bumps on my forearms and, just Friday, my Hematologist also did not connect them to my PV. She did suggest having one biopsied. As well, the underside of my forearms seem swollen and I notice that this does come and go. While the lumps do not always hurt, even when pressed, there is often pain and discomfort and sometimes so intense I cannot ignore it. I’ve had this since being diagnosed w/PV in 2009 and frequently use a pillow under my arms, even when sitting in a chair. Laying my arms on the arms of a chair is almost impossible. My arms get very tired very easily. Is it part of the Erythromelalgia, which I do havae but do not suffer in the extreme sense?

  5. Again thank you to all the doctors for all their answers. This was very valuable to me.

  6. A huge thank you to all the wonderful MPN specialist physicians who are so generously give their time and share their expertise to provide the MPN community with this amazing resource of a free online clinic. Also, a very big thank you to Zhen for instigating the online clinic and for all the work involved in collating and publishing the questions and answers, so we can all benefit from them.

    • Thanks to the quiet and efficient efforts of working RN Mary Morochnick, an MPN caregiver, the MPNclinic closes its ultimate doctor-patient link. Mary, Project Coordinator, logs in all patient questions and forwards physician responses to patients as they are received We all benefit massively from this profound base of MPN knowledge created by the Roundtable, but it is a free clinic whose primary purpose is providing counsel to patients. And for that, Mary is our indispensable on-call support. Thank you, Mary.

  7. A thank you to all of the Doctor’s for taking the time out of their busy day to supply us with such invaluable information.

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