International MPN News, Science & Opinion

MPNclinic Special Section — September, 2012

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Dr. Richard Silver
Weill-Cornell

Dr. Srdan Verstovsek
MD Anderson

Dr. Ruben Mesa
Mayo Clinic

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

Dr. Attilio Orazi
Weill-Cornell

Dr. Ross Levine
Sloan Kettering

    

Dr. Jason R. Gotlib,
Stanford

Questions may be sent to MPNclinic@gmail.com.

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

Ruben Mesa = RM Richard Silver= RS Srdan Verstovsek= SV

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.

 

When is Pegasys use appropriate?

J.G.,  Eastern US I have found little recently published regarding Pegasys for MF patients. What criteria are desired for this therapy?

SV: Pegasys is one of the therapeutic options for patients with MF. there are no specific criteria for its use. However, it is known that interferon (Pegasys is a long-acting form of interferon) may help particularly in earlier stage of MF, in cases where there are too many cells in blood (i.e. proliferative phase of the disease) and low grade fibrosis in the bone marrow (vs. advanced MF with low blood cell count and very significant fibrosis in the bone marrow)

CH:: PEGASYS is an exciting treatment option, it is important to remember especially for MF it is really experimental. My own view is it is likely to work better for patients with early MF. My other concerns are side effects, I don’t think the data to date are compelling enough for a patient with significant side effects to stay on this therapy. Personally I am very excited that we are recruiting into a study comparing PEGASYS with HC in ET and PV.

Myelofibrosis with good counts. Is Pegasys an option?

D.C., Colorado… I was diagnosed with PMF in June of 2009; I am 56 yo with no other medical problems. A BMB concluded the PMF diagnosis with moderate to markedly increased reticulin fibrosis, 40% cellular marrow with abnormal clusters of large megakaryocytes, convoluted nuclei and abundant cytoplasm, no abnormal blasts. I have been on HU and aspirin since this time with eventually taking 500 mg. of HU five times a week and 1000 mg. twice a week. My doctor has told me that he would most likely be able to get Pegasys for me but with my counts being fairly good I am not sure if I want to “rock the boat” on the small hope that Pegasys will either reverse my fibrosis or hold it off for a while. I have been battling this decision…what would your advice be? Thank you so much for being willing to answer questions….wow!

CH: You are a young patient with what appears to be low risk MF, as I tell my patients, sometimes choosing the best treatment is finding the one whose side effect profile is best suited to you and also most acceptable. You could consider a trial of PEGASYS.  If it suits you well then fine, if not you could return to HC. Both are good treatments.

SV: Of course, there are no rules that one can apply in this particular situation, and approach needs to be individualized based on detailed review of the particular patient’s situation, pros and cons of proposed change, desires of a patient, and opinion of an involved physician. Detailed medical history and review of medications would be needed to see whether use of interferon is prudent. I don’t think one can give an advice easily, without proper detailed assessment.

Long-term use of Anagrelide…what are the effects?

A.S., Cambs UK:..Can I ask if there are any statistics or studies on the link of long term use of anagrelide with  transformation or progression from ET to MF?

CH:  The PT-1 study suggests that there is more risk of myelofibrotic transformation from ET to MF with anagrelide than with HC. This result came from 400 patients over 3.25 years. The only other study (anahydret) was not powered to demonstrate a difference. There is an on-going study EXELs a long term observational study in Europe following ET patients receiving therapy which should help show more results.

AO: There is no convincing evidence that anagrelide favors myelofibrotic progression in cases of “true” ET diagnosed in accordance with WHO 2008. Most cases of ET in which myelofibrotic progression was described were in reality early phase PMF (prefibrotic or minimally fibrotic) from the very beginning.  No fibrogenic potential of anagrelide was shown in the preliminary results of the large ANIDRET Study https://ash.confex.com/ash/2008/webprogram/Paper11545.html.  However, irrespectively of the anagrelide issue, there is a small risk of myelofibrotic progression even in true ET which is less than 1% at ten years but 9.3% at fifteen years [see: Barbui T, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29:3179-84].

Link between interferon and thyroid problems?

A.S., UK… Are any studies  or stats available on the link  of the use of Interferon with thyroid dysfunction?

CH: Thyroid dysfunction is a well-known complication of interferon use. Both over and under active thyroid conditions have been reported.

SV: interferon can cause abnormality of a thyroid function, this is known rare side effect of interferon

PV and lymphoma – what is my outlook?

H.K., Melbourne, Australia…I have both PV (ET -2003) and follicular lymphoma (2007).  Have no symptoms and am in w & w as I have refused hydroxyurea & interpheron due to extreme sensitivity to chemicals. Now that I’m turning 60 I am re-evaluating. I am on aspirin and had 2 venesections last year when my ET morphed into PV. My haemocrit went through the floor after the venesections. Platelets 850. Lymphoma shows no change since first diagnosis. Extremely indolent. Have you ever heard of anyone with these 2 cancers? What prognosis is the most likely?

SV: it has been well described that patients with MPN have higher chance of having lymphoid disease. prognosis is related to the type of MPN and type of lymphoma, not to the fact that both are present at the same time. in this case it seems that both are indolent at present

CH: Sorry to hear about this. There is an association between PV and lymphoid disorders such as follicular lymphoma. I wouldn’t like to comment on your prognosis question because really I would need a lot of medical information and a proper hands on evaluation. Both diseases have good treatment options if needed.

Night sweats.

K.A, Rochester MN….I found out I had ET in 2004.In 2007 I started bleeding and was diagnosed with mesenteric ischemia.From then on I was put on Warfarin ,Hydroxyurea and aspirin and  haven’t had any problems except night sweats.Is there anything I can try to stop these night sweats.I go to sleep and wake up 5 – 10 minutes later sweating and then every two hours.After 6 a.m. I am pretty much ok except once in a while I get it about 9 p.m.This has gone on every night since 2004. .I get very fatigued during the day which I am sure some has to do with not getting a good night’s sleep.I would like to go back to work part time but right now that seems impossible. I would appreciate any kind of suggestions. My hemotologist is at the Mayo Clinic for this.He has suggested to me to try an anti depressant but I do not like the thought of trying that being it can cause problems sleeping, interfere with my blood thinner and cause high blood pressure which I already take meds for. I am hoping you have other suggestions to try.

RM:  Night sweats can be a problematic issue in myeloproliferative neoplasms.  We have been involved in assessing the symptoms associated with MPNs since 2007 in combination with colleagues and investigators from around the world.  Night sweats are most common in patients with myelofibrosis (or those with post-PV and post-ET myelofibrosis) but still can be present in individuals with ET or P vera.

These can vary in terms of how they affect individuals.  They can range from being a mild sensation of warmth to being drenching hot flashes at night, sometimes with enough perspiration to require individuals to change the bed linens.  These likely are a side effect of the myeloproliferation going on in the bone marrow.  We do believe that they likely are related to proteins made from the bone marrow that are circulating in the blood.  These proteins are called cytokines and can lead to a variety of the symptoms associated with the disease.

For women who have undergone menopause, we sometimes do have to distinguish these from hot flashes which can occur from the lack of estrogen.  For individuals who are recently menopausal, it can be difficult to distinguish between the two.  If women have been menopausal in the distant past, we will find that there was a cessation of their hot flashes and then a recurrence.

In terms of options for helping night sweats, this has been an area where the JAK2 inhibitors, whether approved or experimental, have been helpful.  Other medications that have been helpful have been medications that have helped to suppress the myeloproliferation going on in the bone marrow.  There has been benefit that has been experienced with interferon depending on an individual’s clinical situation and other non-MPN medications have included certain antidepressants that have been helpful.  Good therapy of night sweats should be taken into consideration in the broader program in terms of treating the MPN.

CH: Sorry to hear about these troublesome night sweats. They are likely to be associated with your disease but it is worth excluding other factors perhaps hormonal, your thyroid, or diabetes as well as perhaps female hormones for example. Night sweats sometimes respond to drugs like hydroxyurea and very good control of the blood count. If this is really troubling you and it sounds like it is I would ask to be considered perhaps for a trial with a JAK inhibitor since these agents do provide better control of symptoms like sweating. Only your haematologist can tell you if this is appropriate to be considered for you.

Leg ulcers and hydroxyurea.

T.A.,  Perth, Australia… I was diagnosed with ET 4 years ago and was started on lowdose aspirin and as my counts became higher I was placed on hydroxyurea which gave me leg ulcers therefore I was switched to anagrylin.  My blood counts have now dropped from 1.3m to .3 and according to the specialist I should be showing no symptoms at these levels. My problem is I still have severe itching, total exhaustion after 3 hrs trying to work,violent headaches and shortness of breath. Is this in any way normal for ET? I have just had my first bone marrow biopsy and am waiting on the results. Any info you can give me would be great.

RS: Suffice to say,  leg ulcers are a frequent complication seen with hydroxyurea, often overlooked by enthusiastic users of this drug.  It occurs in a frequency of about 15 to 20% of patients.  They also heal slowly.  Often patients are referred by uniformed hematologists to dermatologists who in general have very little idea of this being a complication of hydroxyurea so the medication is continued and various local dermatological medicaments are applied without any effect.  The only way of treating hydroxyurea ulcers is to discontinue the drug.  Healing is slow, unfortunately.  Local wound care should be applied.

SV:There are many possible causes for symptoms reported and one cannot simply say whether they are related to ET or not. Detailed medical history and review of current blood work and medications would be needed. Apparently, involved physician is trying to answer this question as the bone marrow biopsy was just done. Therefore, follow up with him is mandatory, to resolve the issue and try to provide answers.

JG   Regarding your symptoms of headaches, shortness of breath, exhaustion–
a.  Ask your doctor whether you have an elevated red blood cell count, measured by the hemoglobin/hematocrit, and whether there is a role for phlebotomy.  Some patients have an overlap between ET and polycythemia vera (PV), and if the red blood cell count is high, a phlebotomy could be helpful.
b.  What is the dose of anagrelide you are on?  Anagrelide itself can cause headaches and fatigue, and sometimes effects on the heart that could contribute to shortness of breath.
c.  Because myeloproliferative disorders can be associated with blood clots in the arteries or veins, speak to your doctor to determine whether there is any concern for blood clots that can be contributing to your symptoms..

CH: These symptoms do sound bad. My suggestion is you discuss them with your haematologist. Anagrylin may be the cause of some of them – particularly headaches, splitting the dose may help. You need a medical evaluation for shortness of breath and exhaustion. Itching may be your MPN but worth checking other causes too – is it new, what triggers it, is there an associated rash?

PV to ET – what are my options?

S.H., Aliso Viejo, CA… In 2002 I was diagnosed with PV based on an RBC of 21. Today my RBC runs in the 3-3.2 range and my platelets are elevated, at around 500+ using HU (500 mg daily with addl 500 2x wk) . My current hem/onc (not the diagnosing physician) says I’ve converted to ET. As I continue to increase HU to control platelets RBC continues to drop. Anagrelide is not an option. I tried that after a heart attack in 2004 with terrible side effects. Would appreciate any insights you have to offer.

RS: The importance of doing a bone marrow biopsy in all patients with ET has recently been stressed by Thiele and there is an excellent article on this subject by Barbui in the Journal of Clinical Oncology in 2011.  This shows that those patients who present with thrombocytosis may in fact have an early phase of primary myelofibrosis and not ET.  The difference in prognosis is significant and such patients may be candidates for different forms of treatment.  Itching is an unusual complication of essential thrombocythemia.  The distinction of early essential thrombocythemia and early polycythemia vera with pruritus is very common and can only be resolved by performing a red blood cell mass which a number of us believe is a very important adjunct to the diagnosis of patients with myeloproliferative disease.  In general, the development of myelofibrosis occurs 8 to 10 years after the diagnosis of PV in patients who do not receive specific myelosuppressive therapy.  It is for this reason that some of us believe that interferon is the drug of choice in patients with significant phlebotomy requirements from the onset.  Patients with PV who have residual hematopoietic tissue and who have fibrosis in the marrow do respond to interferon and so these patients should be considered, in my opinion, with interferon therapy i.e. in Pegasys or interferon alpha 2b

JAK2 variation and Pegasys.

J.S., Cincinnati… I was diagnosed with PV in 2002 and have had good control of my CBC counts with interferon in the initial years and Pegasys in recent years.  My latest round of Pegasys started in late 2007 with 135 mcg/week and was reduced to 65 mcg/week fairly evenly over that time.  My doctor has started taking JAK2 tests twice a year, based on the good results from the Verstovsek study of Pegasys.  About 9 months ago, my JAK 2 was down to 4%.  Recently, it was up to 14%.  My counts have held steady over the past couple of years, HCT 40-44, platelets 104-180, White count 3.7-4.6.  Before the most recent JAK2 results came back, we had agreed to take a break from the Pegasys to see if the good results would hold steady.  Since the test came back with the increase, my doctor has restarted the Pegasys at 100 mcg per week.

Questions: How much variation is common with JAK2 percentages?  Is a movement from 4% to 14% significant?  Is there a level that causes concern?  What is the best practice concerning Pegasys “breaks”, especially in cases where the CBC numbers are good, but he JAK2 numbers are still fluctuating/increasing? Thank you so much for offering this opportunity?

 SV: Variation in JAK2 percentage is common and one usually follows a trend in change rather than be concerned about one measurement. however, most importantly, percent does not correlate with clinical outcome so there is no reason to be concerned. usually the use of pegasys is based on a clinical need, to control blood cell count, and it is not judged on the JAK2 percentage. traditionally interferon is given continuously, at the lowest active and safe dose, to maintain response, without breaks.

CH: Great news that you are doing so well on PEGASYS, congratulations! You are asking some great questions. JAK2 percentages: We are working on this in the field and the answer is each lab is different. In my lab we only use JAK2 percentage to guide therapy after a transplant. I don’t change PEGASYS dose according to these results since I am not sure we know enough about it. There is no best practice for PEGASYS breaks in our clinic.  We increase gaps and reduce dose once we get to every 4+ weeks I consider stopping, but I discuss and consider each patient individually.

MPN and Rheumatoid Arthritis…any connection?

,R.S., Norwalk, CT...I have ET.  I have been taking Hydrea for 2 years and my blood tests are in the normal range. I am living an active life but stopped working 2 years ago to reduce stress levels. I do get tired and sometime off balance.
Question: I have just been diagnosed with Rheumatoid Arthritis.  Is there a possible connection between these 2 diseases and/or the medications?

RL: There is no clear connection between these two diseases.  However, there is data that by different mechanisms, that JAK2 and JAK1 are involved in both diseases, and JAK inhibitors are being tested both in MPNs and in RA.  So it is possible, depending on how these trials report their results, that a single medicine might help both diseases.

CH: Sorry to hear about the rheumatoid arthritis.  To my knowledge this is unlikely to be connected with your ET.

Genetic markers…an aid to therapy?

 J.C., Cleveland…  My genotype for European Ethnicities is CG    JAK2 V617F-positive myeloproliferative neoplasms. Will knowing the location of the marker help in developing a treatment/cure for PRV?

CH: Yes I believe all this information will ultimately help us to find a cure but we would not base current treatment on this.

RM: The location of the marker does not help in any way now, though many of us are trying to determine how genetic markers influence risk of these diseases.  Right now this has no value in treatments being used or tested in trials

Ever higher doses of hydroxyurea

J.C., Cleveland… I was diagnosed in 1997, my hematologist considers my blood to be very stable however over the years the hydroxyurea has been steadily increased from 500 mg/day to 1500 mg 3x a week and 1000 4x a week. Dosage may go up to 1500 4X a week soon. Hydroxyurea is tolerable but I don’t like to keep having to increase the dosage to control the platelets. The dosage increase is because platelets spike over 400 which is not high for some but causes tingling in my arms, hands, feet and legs. Agrylin did not work, Interferon did not work. Is there any other suggestion or should I continue consuming large amounts of Hydroxyurea?

SV: If hydrea works then one sticks with therapy that does the job. Alternative therapies include chemotherapy agents that are known to increase risk of transformation to acute leukemia, so this is not advisable

CH: Provided there is no other explanation for tingling in your arms, I would continue with the current dose. There is no clear evidence that bigger doses of this drug are more harmful than smaller ones. An expert panel considered 2g per day to be a maximal dose for patients weighing less than 80 kg and 2.5g for those above this weight.

PV, sarcoidosis and now non-Hodgkins lymphoma? 

J.V., W. Australia Dxd with pv 2011, been on hu and interferon pretty much all that time and last week was told i had sarcoidosis, the dr told me he was 99 per cent sure i had nhl, but the last week had a fine needle biopsy and thats where this dxd came from, could this be wrong? I was reading my ct scans and pet scans and they  say in keeping with stage 3

CH: This is clearly a concern I am afraid that your case sounds complicated and sarcoidosis and NHL can show features in common. I would advise a frank conversation with your clinician.  Raise your concerns, take someone else with you to the consultation and write out your questions beforehand.

PV with high platelets, phlebotomy only?

C.G., NAWhat is a platelet count to start treatment for Pv?    Is is 1mm 1.5 or 2 mm?   Is age a factor as well?   The only symptoms I am having is occasional headaches lightheaded dizzy  feeling.  I have 1 mm platelets and am 40 yrs old.  I get phlebotomys when hematocrit is 45 or higher.  Platelets are the only problem so far which have been increasing over the last few years.  Do you wait until a serious Event?  ( seizure stroke clot) before treating w Pegelated interferon

CH: Good question. We have no international agreement on a platelet count to start treatment for PV. Also, in my own practice, I would individualise this for each patient depending on other things. Have they had a clot, are there other vascular risks etc. I would also aim to treat before a serious event, not forgetting that venesection and treatments like aspirin offer protection against most events.

 RM. Perhaps as a broader interpretation of this question, I think the individual would have to discuss what are the goals of therapy for patients with P vera and how does Pegasys potentially play into those roles?  The goals of therapy with P vera have potentially both short-term and long-term goals.  In the short term, therapy of early MPNs, ET, and P vera primarily focus on trying to prevent vascular events, which are blood clots or bleeding.  This could include as well microvascular symptoms or symptoms where blood flow is impeded causing symptoms such as difficulty with headaches, complex headaches, recurrent migraines, difficulties with concentration, erythromelalgia and other difficulties.

Another goal with ET and PV would be to potentially improve the symptoms associated with the disease and a final goal and a goal that at this point does remain more theoretical would be to try to delay progression in the illness.  Pegylated interferon has been shown in single-arm phase 2 studies to help to control counts, help to improve symptoms, may help to improve or decrease the risk of blood clots or bleeding, and that is currently undergoing proof in a randomized clinical trial between Hydrea and pegylated interferon.

Finally, there is speculation and hope that Pegasys may have an impact on delaying progression of the disease, but that still needs to be proven beyond a shadow of a doubt.  The impact of phlebotomy rate and platelet count on both the initiation of Pegasys or the adjustment of the dose is a more individualized decision that should be discussed with the physician and the patient, but those are secondary considerations in terms of creating the overall plan for the patient.

MF, big spleen, no meds, need treatment.

D.P., North Wales…  I am a post PV myelofibrosis patient with an enlarged spleen, anaemia with a haemoglobin reading of 8.7.  I am based in North Wales, UK.  I was diagnosed with ET in 2000, PV in 2005, MF in 2010.  Up until the MF period I have had very limited symptoms and only took baby aspirin during the ET period.  Currently I take no medicines at all.
I am about to start a trial period on EPO to try and raise the haemoglobin.  Apart from the impact of the anaemia on walking uphill, general tiredness etc I have no other symptoms such as bone pain, night sweats etc.  However since my diagnosis of MF in January 2010, my condition has deteriorated and I have yet to meet a haemotologist who knows much about MPNs. Would the panel recommend the use of pegasys to try and halt this deterioration which is presumably caused by the ongoing fibrosis in the bone marrow and its impact on the spleen?  If not, what treatment would you recommend in my situation?

CH: David there are many treatments potentially available for patients with the concerns you describe; which ones to offer depend upon individual patient factors. EPO is a good choice I would say since symptoms of anaemia are the ones which seem to bother you most. Really you ought to have a proper evaluation to individualise treatment perhaps seeking a second opinion at least to set a plan.

Ring sideroblasts and Pegasys

S.S., Michigan… Diagnosed with ET, JAK2 positive (2008)

Pegasys 22.5 MCQ (every other week)  All counts in normal range except  WBC always below normal but function appropriately when necessary. The bone marrow is hypercellular with trilineage hematopoieses and myelofibrosis (grade 2/3 WHO 2008). Latest BMB showed that there is dyserythropoiesis with increased iron storage and occasional ring sideroblasts (<10%) in the aspirate.  No circulating blasts.

My question:  Is it unusual to see increased storage and ring sideroblasts in MPNs and could this be caused by the suppression of the bone marrow due to the Pegasys?  If it is unusual what should be done?

AO: There is limited information. You have normal hemoglobin and a low frequency of ring sideroblasts that is well below the threshold of 15% (used for suspecting an MDS, refractory anemia with ring sideroblasts type). Most likely this is nothing to be too much concerned about. Possible role for interferon. Some of the cancer patients who developed transient ring sideroblasts (>15%) in a MD Anderson study (see ref.) had indeed received interferon (alpha). So it is conceivable that the ring sideroblasts may be due to interferon treatment. If you are worried, an important test to check in occasion of your next marrow is karyotype. In addition, if there is a previous bone marrow to compare it might be useful to know the percentage of ring sideroblasts pretreatment. Reference: Ok CY, et al. Leuk Res. 2011 Dec;35(12):1605-10.

CH: This is very interesting. Ring sideroblasts are red cells with excess iron around their nuclei they look very pretty down the microscope but if there are less than 15% of them generally they are not significant. I am not aware that PEGASYS might increase the chance of seeing them or indeed extra iron in your bone marrow.  I assume this wasn’t seen previously. Difficult to give an opinion here but I would keep an eye open (?)and possibly think about getting checked out for haemochromatosis, an inherited iron loading condition.

RS: This case demonstrates the importance of the bone marrow biopsy in all patients with ET especially at diagnosis.  The World Health Organization criteria are quite specific in saying that in general, patients with ET have normal cellularity whereas in patients with early myelofibrosis, the marrow is hypercellular with evidence of increased granulopoiesis and erythropoiesis.  With early PV a definite increase in reticulum fiber may be seen.  Of course megakaryocyte morphology in the hands of experts such as ourselves can be very helpful although it is a matter of contention in certain centers in Europe.  The findings of siderocytes is troubling since this is not part and parcel of the MPD picture.  Certainly FISH tests on marrow cytogenetics should be performed at the very least.

Why can’t we donate blood?

S.A.Wigan, UK…   (1) Why can’t we donate blood or bone marrow? If the effect of our disorder (PV) is that we produce too many red blood cells surely this would benefit those requiring blood products?  at the same time i am having a venisection for too high a Hct there are people with single figure Hct receiving blood products.  The surplus (iron rich) blood is a consequence of the disorder and not the cause, so why does the NHS not utilise this rather than incinerate our blood, or are we misinformed and it can be transmitted via blood transfer such as blood transfusion….

CH:  Unfortunately you can’t donate blood for transfusion to other patients because you have a blood disorder. You may find that the venesected blood could be used for other purposes. For example our lab use it to check normal ranges etc.

RM.  First, as always, I am impressed by individual’s altruism in that even while facing a blood illness, with their spirit of altruism, they still wish to donate blood or marrow.  First, with marrow, there is of course concern that an individual with an MPN would potentially have the MPN present in the stem cells that would be donated in bone marrow and, on this basis, potentially impact the individual who would receive the cells.  Even if the donor was in an earlier phase of MPNs, it still could be quite problematic in terms of the recipient. So I would say, in terms of bone marrow, there is concern that it could be harmful to the recipient.

Now in terms of blood, I think the issue is more complicated.  The blood of individuals with MPNs is highly unlikely to be contagious in any way and certainly unlikely to be able to transmit the disease.  Indeed, individuals with P vera who have had phlebotomies, if this blood was given to recipients who needed a blood transfusion, the likelihood of transmitting anything harmful is probably exceedingly low.

That being said, the American Association of Blood Banks has very conservative guidelines that they follow which can include multiple years of being disqualified as a blood donor for international travel to places even such as Mexico or the UK.  So the real reason that patients can’t donate blood is primarily because of the strict guidelines the American Association of Blood Bank pursues to try to have the safest blood supply possible, even though the likelihood of harm to any recipient really is probably not a major factor.

RS: The question why phlebotomy blood cannot be used for patients in dire need because of thrombocytopenia, leukopenia or anemia is an interesting one.  For many years when I was a resident and junior attending, polycythemia vera blood was highly sought after.  Suddenly, it could no longer used therapeutically.  As I remember it, through long ago conversations, polycythemic blood was transfused to a “normal patient” who subsequently developed polycythemia vera.  Apparently, there was a law suit and the possibility of some transmissible factor in the polycythemic blood causing polycythemia in a normal patient could not be conclusively excluded.

For that reason, polycythemic blood was no longer accepted.  This is a pity, since polycythemic blood is rich in red cells, platelets and white blood cells.  The white cells are physiologically active and is one of the reasons polycythemia vera patients do not develop infections.

Refused venesection.

S.A., UK...I’ve been 0.001 away from target threshold Hct and despite being symptomatic the local hospital has refused venosection , requiring  unecessary conflict to get a venosection done – is there a central info base for medical people to be referred to? To be refused treatment after 13 years effective self management is both humiliating, frustrating and stressful.

CH: Sorry you have experienced this I understand it is exasperating unfortunately we do not have a central information base but perhaps find a member of the local team who listens to you best and try to arrange to see them?

Does Pegasys work?

A.M., Massachusetts… As someone who has used pegylated interferon (aka Pegasys) for more than two years now, I’m more than a little interested in knowing more numbers with regard to this drug. Assuming that this is medical information in addition to proprietary info, I’d like to know a bit more about what the medical community has found out with regard to its efficacy.

CH: There have been several papers showing efficiency of pegasys from French and MD Anderson groups and most recently an international consortium convened by Ruben Mesa.

JAK2+ runs in the family.

J.P., Michigan…  I am a 53 year old female diagnosed with JAK2+ ET about 3 years ago.  My 72 year old mother was just diagnosed with JAK2+ ET as well.  Should my 4 grown children and 8 grandchildren be tested that or wait for symptoms to appear?

RL: Although family members of MPN patients have a 3-5 fold increased risk of developing MPN, and you have a family history, I would not test your family for JAK2. I would consider routine blood counts in the adult family members. 

CH: About 1 in 8 ET patients will have an affected family member just as you do. My advice would be to raise awareness in your family and that if members have a blood test it should be checked for signs of MPN. I would not advise mass testing of your family however mainly because a normal result now would not necessarily remain normal and particularly young children often have vigorous bone marrows with high platelet counts which return to normal which can cause a lot of anxiety. So I would test in two scenarios: first if there are symptoms and second if there is a risk situation e.g., a young woman needing contraception or a planned surgery.

High platelets, on Anagrelide…

C.M., New Jersey.. . On Anagrelide for 5 years 4 mg a day. My platelet number is 843. No symptoms other than the high platelet number. I see a hematologist regularly. I sent a saliva sample to 23 and me. Was offered to participate in jakafi clinical trial but chose not to participate at this time. What is best treatment for me? What can I expect? How does this progress? Should I travel outside US?

 CH: The best treatment is one which is individually tailored to you and reviewed to ensure it is still the right treatment. I would think you should be aiming for a better platelet number (sub 400 as a rule) however there may be excellent reasons for being kept at the level you are currently at. I can’t see any reason at the moment to travel outside the US.

 PV, no meds, what next?

A.F., Lousiana…I am a 47 year old female, in excellent health,  diagnosed with polyscytemia rubra vera 3 years ago. I see my hematologist every 6 months.  My only treatment is 1 baby asprin a day.   My concerns are: What should I be looking for, physical sign and symptoms, as indicators the PV is progressing? What should I be doing to prevent progression? Where can I find simple information about this condition?

CH: Well you have found MPNforum. As a source of information there are other websites linked to that one as well. The first thing to say is your disease is unlikely to progress fast if indeed it does progress. It is important to be aware of signs of a blood clot – usually pain and swelling (not always both present). Patients who progress usually start to notice a change, usually, but not always, a drop in blood counts, perhaps a fullness where the spleen is (left upper abdomen) and increasing symptoms particularly weight loss, bone pain, sweating etc. To prevent progression and prevent thrombosis it is important to have as active and healthy a lifestyle as possible. No drug treatments have been shown to delay progression.

Liver enlarged post-splenectomy

J.H., WisconsinSince my splenectomy 5 years ago my liver is getting larger.  What is the best line of treatment for this?  I began Jakafi 2 weeks ago.  My hematologist is advising me to get checked out at Mayo again.  Since you are not in Rochester anymore I must see someone else.  Who would you recommend.  Since United health care has recently approved Pegasys I would like to go back on that.  I will see my hem on the 6th.  My counts are good, in fact the hemaglobin has been slightly above average for the last months, plts are normal wbc is high most likely due to nucleated reds.  I have taken diuretics since the splenectomy, but my legs are swelling more with water retention in the last month. Any advice for us?

CHThere are several different treatments for liver enlargement after splenectomy I think Jakafi is reasonable to try in this setting but there are others.  You mention interferon but hydrea and 2-CDA have also been used. If you are stable I would try Jakafi for at least 6 weeks before deciding if it works or not.  Livers respond more slowly than spleens and some patients’ spleens take longer than12 weeks to respond.  It would be important to get a proper check of the water retention.

MF – spleen shrinking, anemia increasing.

F.M., Ontario, CanI have had PV/MF for the past 21 years. I have been on 90 micro gm of  Pegasys for the past 3 years. My last cbc showed the white cells at 16, platelets at 350 and Hgb at 104, the lowest that it has ever been!  In the past 6 months I have increasingly been feeling chronic joint and muscle pain (in conjunction with the Hgb dropping from 127 to 104) and the Spleen changing from 23cm to 15cm. The white cells and platelets dropping very marginally.

Is it possible that my dropping Hgb is caused by the Spleen getting smaller? Is the spleen helping my struggling bone marrow make blood cells? I have not had a BMB for the past 5 years.

CH: Hello Frank it sounds as though things are going well with your spleen but less well  with your Hgb and symptoms. I would say it will be really important to get checked out for other causes of anaemia (for example iron deficiency or thyroid disease linked to the interferon) and joint/muscle pain.

A difficult case…

 Dr. M. G. Baltimore… A 75 year old man was referred because on a preop CBC he was found to have a WBC of 45K with a H/H of 11.4/34.3 and a platelet count of 296. On smear review he has neutrophilia with a mild left shift,  monocytosis of 13% and a rare blast. He feels absolutely well.  No fever, chills,  anorexia, pruritus.  He is active,  still working full time in an office setting.PE is completely negative.  No lymphadenopathy;  no hepatosplenomegaly. Comp met profile is unremarkable.Bone Marrow:  Markedly hypercellular  (95%.)  Atypical megakaryocytes.  Reticulin stain shows very mild increase in reticulin fibrosis. Flow cytometry: No increase in blasts.  Half of the granulocytes express CD56. Cytogenetics:  Normal karyotype. Fish for BCR/ABL is negative.  MDS FISH panel is negative. JAK2V617,  JAK2exon12 and MPL are all negative.Slides were reviewed at Hopkins Conclusion:  ” difficult case to classify.” the pathologist ruled out CMML was because there was no monocytosis in the marrow.

Any suggestions as to furthur diagnostic tests?

AO: The case seems to fit best CMML-1. PB and bone marrow should be reviewed to confirm monocytosis (esterase and/or CD14 helps on the bone marrow). CD56 expression in granulocytes (aberrant) and monocytes  is quite common in CMML. A small proportion of CMML with WBC  >13 x10/9/L (proliferative subtype) may have a proportion of  megs. “MPN-like”  in addition to the more common dwarf forms.  Some of these proliferative CMML may have a JAK2 mutation (rare) other may have RAS mutation.

The presence of bone marrow monocytosis can be subtle. Its identification is greatly aided by esterase and/or CD14 immunostaining. In general, if the PB monocytosis is persistent  (>3 months) this might suffice for diagnosing CMML based on PB findings. The alternative is a diagnosis of MDS/MPN, unclassifiable, a heterogeneous group of neoplasms which besides RARS-T, also includes  truly unclassifiable cases with MDS/MPN overlap features. There is no much information on how to treat MDS/MPN, unclassifiable. My guess these cases  are approached similarly to CMML, tailoring the treatment to the predominant clinical manifestation(s).

MPNforum Project Coordinator:  Mary Morochnick, R.N.

Note:  Please submit your concise questions to MPNclinic@gmail.com.  Responses from Roundtable physicians are immediately forwarded to patients, prior to publication.
Take me back to the Contents

© MPNforum.com, 2012. Unauthorized use and/or duplication of this material without express and written permission is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to MPNforum.com with appropriate and specific direction to the original content.

 

Comments on: "MPNclinic Special Section — September, 2012" (2)

  1. Leeya James said:

    Just read all this myself! Not sure how I missed it but these are wonderful, thoughtful replies! Thanks so much to all the doctors and of course to Zhen for bringing this about!

  2. Thank you so much for this. I have to say I found it by accident. I was waiting for an announcement with a link. Perhaps you should publicize it again? . . .better?

    Brenda Pena

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