CancerConnect Presents: Ask the Expert with Dr. Mesa
Ruben A. Mesa, MD recently participated in the CancerConnect guest moderator series on myeloproliferative neoplasms (MPN). Dr. Mesa answered your questions about polycythemia vera, essential thrombocythemia and myelofibrosis in the MPN Support Community on CancerConnect. CancerConnect is a safe and private online support community for cancer patients and caregivers.
Dr. Mesa is is a medical oncologist at the Mayo Clinic in Scottsdale, AZ. He is committed to improving therapies and quality of life for patients with myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis. Click here for Dr. Mesa’s bio.
Join us in the MPN Support Community on CancerConnect to view the entire Ask the Expert session with Dr. Mesa.
Myelofibrosis Questions
Question About Molecular Status of CALR, JAK2, and MPL: With all the clinical trials in phase 2 & 3, are there any that seem to work better for those with CALR, JAK2 or MPL?
Dr. Mesa’s Response: At this moment in time the molecular status of CALR, JAK2 and MPL, we do not definitively nor have an impact on choice of therapy. There are some early indications that patients with CALR might have very good responses to interferon and this may be relevant for MPDRCs clinical trials with interferon but it is unclear whether there is a differential benefit. In the past, molecular signature has not been crucial for choosing therapy.
Question About CALR Status: If I knew my CALR status, would that change my treatment options? Is the CALR mutation test routine yet? I am having trouble getting my insurance to pay for the test and am also wondering if there are links to any articles I could provide to ask them to reconsider?
Dr. Mesa’s Response: At the time being, CALR status may have implications regarding prognosis in a select group of patients but would not be relevant in terms of choice of therapy yet for the moment. This may evolve and may play a role in terms of choice of stem cell transplantation.
Question about SCT: My sibling and I are a 10/10 match for SCT. I have Intermediate 1 Myelofibrosis. Can my sibling’s stem cells be frozen for possible use at a later date?
Dr. Mesa’s Response: Stem cells can be frozen for use at a later date, although whether this would be supported by your physician or insurance company in terms of the expense is less than clear. In general, this is typically not done unless a transplant is clearly planned and there are significant health concerns regarding the donor.
Question about half- match transplants: Half match transplants seem to be an exciting new development. What are your thoughts on half match transplants with patients with Myelofibrois?
Dr. Mesa’s Response: Half match transplants are highly investigational and do hold promise but need to be looked at as investigational. There is real concern about graft failure in patients with myelofibrosis and in unmatched transplants this is considered a higher risk.
Question about Treatment Options: I have symptomatic MF that is JAK +. My doctor started me on Busulfan 6 weeks ago but I don’t feel any better. Everything I find on the web seems to suggest I should be treated with Jakafi; I can’t find anything on Busulfan and I am trying to understand the rational for using Busulfan.
Dr. Mesa’s Response: It is best not to advise you how to choose medical care specifically from such an internet-based question, although I will say that in terms of standard treatment guidelines in terms of Busulfan, Jakafi (ruxolitinib) is the only FDA-approved therapy for myelofibrosis so you may well benefit from a second opinion who considers all aspects in your case to see whether you are on the right choice of therapy.
Question about Vidaza and White Blood Cell Counts: I am in my 6th cycle of Vidaza for CMML and MF. My white cells/ANC started dropping on the 5th day of chemo and I have had to take numerous Neupogen injections. My Vidaza dose has been reduced and I am wondering how this affects efficacy and if I can expect my wbc’s to improve with Neupogen so that I can continue the planned dose and schedule?
Dr. Mesa’s Response: In general, growth factors are not used in support of azacytidine (Vidaza) and indeed improvement in white count is one of the long term goals of azacytidine. If the white blood cell count continues to be low in the face of therapy with azacytidine, it may be an indication to consider particularly after six cycles whether an alternative approach should be explored.
Question about When to Start Treatment: I am 60 years old and was diagnosed with Myelofibrosis a few years ago after having ET for at least 25 years. Anemia is getting lower 9.9, blasts in blood 3%, slightly enlarged spleen, some bone pain. I’ve never been treated with anything but aspirin. At what point do my symptoms trigger treatment other than aspirin and what are my treatment options and their side effects?
Dr. Mesa’s Response: Given the challenges you describe, it would seem that some therapy other than aspirin should be considered. It would be unwise for me and for you, for me to recommend which therapy you should receive, but I would say based on your age, the development of anemia, the increase in the blasts, and the symptoms that you have, we would have concerns about the risks with your disease and need to come up with a much more comprehensive plan.
Questions about Treatment Decision Making: I am a 65 year old female diagnosed with ET last year. Platelets 1249; rest of CBC within normal limits. Asymptomatic at diagnosis and now. Started on 500mg/day hydroxyurea and added anagrelide (platelets at 1188). BMX in November showed “patchy MF1 fibrosis.” Tested negative for JAK 2, MPL, and CALR. Now on 2mg AG/day and 500mg HU 3X week. I am concerned about reports of association of increasing fibrosis levels with AG. (1) Would you recommend periodic BMX and at what intervals? I’m thinking about asking my doc to do one this Nov. (2) In your patients, have you seen increases in fibrosis in ET with AG? (3) My hematologist is hesitant to consider Pegasys because of my age as studies have been conducted in younger patients. Do you believe age is a barrier to Pegasys efficacy or safety? Thank you!
Dr. Mesa’s Response: I prefer not to advise you specifically what to do in terms of your care but will answer the general questions. First, pegylated interferon (Pegasys) can be an option for patients who are evolving into myelofibrosis or having some degree of fibrosis that is still viewed as somewhat of an experimental indication for the drug but is well worth discussing. There is currently a clinical trial through the MPD Research Consortium that may be a consideration. Second, anagrelide is a drug that is approved for ET and has been found to be safe. It can lead to an increase in fibrosis in the bone marrow, at least in clinical studies. Whether that is detrimental to the patients over time, that has not been demonstrated.
Question about MF Risk Groups and Prognosis: Can you discuss how risk groups are determined: low, intermediate, or high for primary myelofibrosis and associated prognosis?
Dr. Mesa’s Response: There are multiple different prognostic scoring systems with the DIPSS and DIPSS+ being primarily used. They identify that increasing age, higher white counts, constitutional symptoms, blasts in the peripheral blood, anemia, transfusion dependence, chromosome changes and low platelets all are prognostic factors and with these one can generate a score that can at least give a general impression on overall prognosis for individuals. It is best to do this in the context of discussions with your physicians in that there are other factors that need to be considered.
Polycythemia Vera Questions
Question about Charcoal and Chlorophyll: Do charcoal and chlorophyll help PV? Is it safe to take?
Dr. Mesa’s Response: I am afraid I am unaware of specific information regarding charcoal and chlorophyll in patients with polycythemia vera. I am not aware of any formal studies looking at this as therapy for polycythemia vera. That is not to say that there may not be benefits, there is just no scientific analysis that I can refer to.
Question about JAK2 Status: My diagnosis seems to have changed, Firstly, it was said that I have Polycythemia Vera, but no JAK2 was detected, now my last letter from my hematologist stated I was JAK 2 positive now. Do you know why this could happen?
Dr. Mesa’s Response: The blood tests for JAK2 have improved over time so it is found that we are now finding some individuals with low level of JAK2 positivity that did not have it in the past. This may represent a change in the lab test as opposed to a change in your disease itself.
Question about Symptom Management: I have PV and ET, Jak2V617F positive. My bones ache terribly and my itchiness is bad too. How can I reduce these symptoms?
Dr. Mesa’s Response: It sounds like you are having difficulty with symptoms with your JAK2 mutated polycythemia vera. For this, there would be potential therapies with either standard cytoreductive therapy such as interferon and the MPD Research Consortium studies or there are JAK2 inhibitor trials which are ongoing, the current one being with Momelotinib in patients with polycythemia vera. In the future, there may well be FDA approval for Jakafi in polycythemia vera and at that time that might become a consideration.
Question about Skin Symptom: I was diagnosed about 2 years ago with MPN unclassified. I do not appear to be having many symptoms, however, I have many small mauve/purple dots/spots, and also sporadic larger red spots, are these a characteristic of this disorder or is it not connected?
Dr. Mesa’s Response: It is difficult to comment on skin changes by an e-mail question but there are times that patients with diseases such as an MPN can have skin-related changes whether they be painful such as erythromelalgia or even infiltration of other cells. I would recommend you visit with a dermatologist and have these evaluated.
Question about Treatment Options: My husband was diagnosed with ET about 3 years ago. According to our new hematologist, it has progressed to PV. His CBc is elevated with HCT 60,000. His platelets are now 1,400,000. He is unable to take hydroxyurea due to severe adverse reaction of high fevers and flu symptoms. Anagrelide caused severe headaches and now he is going for a phlebotomy weekly to reduce HCT (but may not help the high platelets). The hematologist is hoping to get him on Jakafi. My husband chose not to treat for 3 years after the medications made him sick but now he is 67, no major risk factors (he is thin, eats well, non-smoking). We are concerned about high risk for CVA, Cardiac events etc. He used to be very active, now he is tired all the time, has severe headaches, gout symptoms and weight loss along with itchy skin. What treatment options should we consider next, including clinical trials? Also, holistically are there any herbal things that may help? What about diet?
Dr. Mesa’s Response: Overall, it seems that your husband has P vera and has failed hydroxyurea and is having difficulties. It is unwise for me to recommend specifically which therapy to have in the setting of an e-mail question; that being said, I do think that medications certainly should be considered and be a discussion for your husband. Jakafi, which your husband’s physician has mentioned, has been the subject of clinical trials and most recently we did report on the response study of people like your husband who did seem to benefit. This may well become FDA approved in the future and certainly your physician can try to get approval from your insurance company to cover in the off study setting at the current time. Additionally, there are ongoing clinical trials of JAK2 inhibitors in patients with PV, most specifically one with Momelotinib which is ongoing with a variety of national sites and that might be a consideration.
Essential Thrombocythemia Questions
Question about Transplant: My wife is treated with ET since for the last 4 months with hydroxyurea, she is Jak-2 and BCR-ABL Negative. I want to know whether mini bone marrow transplant can cure the ET and whether or not there are other curative treatment options?
Dr. Mesa’s Response: In general, we reserve allogenic transplant for patients only who have progressed to myelofibrosis and we fear that their disease might become life threatening in a handful of years. This is based on the risks of allotransplant and in general is not considered for patients with ET, not that anyone wants to deny patients with ET the potential of curative therapy but really the risks of an allotransplant really exceed the risks of ET. I am hopeful that in the future we will have even better and more effective therapies against ET so that such a drastic move such as stem cell transplant would not need to be considered.
Question about Erythromelalgia: I have ET and recently started getting symptoms of erythromelalgia -sharp intermittent pain on top of left foot. I have been using acupuncture and Chinese herbs. Are there treatment options that could help with the pain? My doctor wants me on hydroxyurea.
Dr. Mesa’s Response: Erythromelalgia is a typical and can be a difficult symptom with essential thrombocythemia. I would leave it to your physician to recommend the optimal therapy for you, but individuals in the past have found benefit to aspirin with this particular difficulty as well as cytoreduction. The choice of cytoreduction is its own conversation with your physician between the three most commonly used agents of hydroxyurea, anagrelide and interferon.
Question about Status: Have you ever seen a patient with a PDGFRB ET, JAK2 negative with normal eos?
Dr. Mesa’s Response: It is difficult to give an accurate diagnosis by an e-mail comment. The mutations in PDGFR beta can be associated with a spectrum of myeloid malignancies and from what you describe may not classically fall into the exact category of ET but may be a slight variant. I think the calreticulin mutation might be helpful to be obtained in this case.
Question about Bone Pain: I have PV and ET, I am on hydroxyruea and pegasys interferon, telfast for itching and zyrtec. What could be causing bone pain?
Dr. Mesa’s Response: PV and ET patients both can experience bone pain even in the setting of therapy with hydroxyurea and pegylated interferon. We work to try to achieve optimal analgesia and sometimes see whether there is opportunity in terms of Hydrea and Pegasys dosing and whether other medications could be considered.
Questions About ET: I am a 69 year old female diagnosed with ET one and a half years ago with a Jak2 mutation. I take low dose aspirin daily. My platelet count has gone from 630 to 850 over this time with minimal and intermittent symptom of sharp pain on top of left foot. Otherwise very healthy and active lifestyle. I have several questions.
a. Is there anything that can get my platelet counts down?
b. Are there any evidence-based complementary/integrative strategies that help individuals with ET? (Chinese herbs,acupuncture, medical marijuana) for ET?
c. Since age seems to place me at high risk what can I be doing to decrease risk of a blood clot?
d. Are there any clinical trials you would recommend?
e. What should I be looking for in determining a serious medical event?
f. As numbers go up and I assume symptoms as well what is the next thing to do?
Dr. Mesa’s Response:
a: Currently the three main medications utilized for cytoreduction in ET would be hydroxyurea, interferon and anagrelide. Which of these is most appropriate for you should be a discussion between you and your physician.
b: I do believe that there are complementary and integrative strategies that can be helpful to dealing with stress and to promote wellness in patients who have ET. I cannot recommend any specific therapy that has directly decreased the platelet counts into the normal range or decreased the risk of vascular events.
c: Decreasing the risk of vascular events in patients with ET is a combination of consideration of aspirin, selective use of cytoreduction but as well as people being physically active and taking measures during periods of increased risk of blood clots such as getting up frequently during air travel, drinking plenty of water and prophylaxis during elective surgical procedures.
d: There are potentially clinical trials of which you might benefit, including the MPD-RC 112 study looking at up front therapy for patients with high risk ET and I would recommend you go to www.mpd-rc.org to investigate possible sites.
e: The risk with ET, in particular, is that around vascular events and one would really look for any unexpected signs or symptoms in combination with guidance from your physician. A swollen leg, pain in the leg, chest pain, shortness of breath, visual changes, a whole constellation of things which would go along with difficulties with blood flow.
f: Your physician really should sit down with you and devise a comprehensive plan, both in the short and long-term, for the ET trying to prevent risk of vascular events while being cognizant of risk of long-term progression.
Question about Latest Research in ET: Please speak about latest research for cures/treatment for ET?
Dr. Mesa’s Response: At the moment we do not have a cure for ET; we hope that this will change over time. Therapy for ET at the moment, by current guidelines, includes three available agents: hydroxyurea, interferon or anagrelide. They each have their pluses and minuses in terms of activity and side effects as well as availability and complexity of taking them. Which one is most appropriate for you is an in-depth discussion to be held with your physician or with an MPN focused investigator.
The Ask the Expert Guest Moderator is not intended to be a substitute for healthcare professional medical advice, diagnosis, or treatment. Speak to your healthcare provider about any questions you may have regarding your health.