MPNclinic MPNclinic MPNclinic MPNclinic
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
Clinical trial for polycythemia vera…
27. Sherri Pruce, Pittsburgh… My mom was recently diagnosed with post polycythemia myelofibrosis at the Hillman Cancer Center in Pittsburgh, PA. Her doctor recommended for us to take her to see Dr. Tefferi at the Rochester, MN Mayo Clinic. I took her on June 14 and 15th and she had extensive blood work and a third bone marrow biopsy …. Dr. Tefferi gave us all of the paperwork to start a clinical trial Multiple Ascending Dose of BMS-911543. It has been three weeks since her appointment and she came home with no medicine or no help. Enrolling into this clinical trial will require her to stay there for a month and also make monthly trips to MN from Pittsburgh, PA.
Today I found online another clinical trial for An Open Label Study of INCB039110 Administered Orally in Patients With Myelofibrosis. The details state that there will be a location in Pittsburgh, PA but not yet recruiting. Is there any information on this trial as to which option is better for her? She’s been on no medicines for her prior polycythemia vera or the myelofibrosis. her spleen is enlarged to about 25 cm and she is now transfusion dependent. Shehas had 10 units since April 1st. I’m trying to seek out the best care for her and not sure how long she can keep waiting with no help?
RM: In the setting of progressive polycythemia vera with enlarging spleen and transfusion dependence, this is clearly a challenging scenario in which the patient is clearly affected in a way that is concerning. The appropriate intervention, whether it be an available current medical therapy, a clinical trial or bone marrow transplant would depend upon the individual’s age and how they are doing. Given the complexity of the options, I do think that a face-to-face consultation with an MPN expert, but closest to your area, would be advisable in that there are really a variety of options, but based on your mother’s overall health, her age, and other diseases affecting her would impact which of these options are best chosen.
CH: Sorry to hear your mum is facing these difficulties. I am not aware of details of either of these trials but your hematologist should be able to help you with these. I think it is important to think about what the key issues are that you would seek to improve an example might be transfusion or symptoms. A balance of options could be available. You don’t mention how old your mum is but if she is fit and less than 70 a transplant might be considered too.
SV: BMS-911543 is a medication that belongs to a group of medications called JAK inhibitors. INCB039110 belongs to the same group. In November of last year one of the JAK inhibitors was approved and it is available as commercial medications to patients with myelofibrosis in the USA; it is called Jakafi or ruxolitinib. To receive Jakafi you do not need to travel anywhere, your doctor can easily prescribe it.
Nattokinase and ET?….
28. Marleque, Denver, Colorado… Is it safe to take Nattokinase with a diagnosis of E.T.? It has reduced platelets in 4 weeks and has continued to do so for 3years. At 1million, now 505
CH: I have no experience of this agent but I do see some literature of its lack of efficacy in precventing heart disease and risk of hemorrhage when combined with aspirin. So I would avoid combining the agents and not use if you have had bleeding with regard to reducing platelets I haven’t seen this.
(Editor’s note: To help the Panel respond to questions as quickly as possible, please limit inquiries to a single question with the applicable background briefly described. Thank you.)
Essential thrombocythemia, multiple questions…?
29. Anthony Simcoe, Sydney Australia…
…I am a 43 year old male in Sydney Australia with ET – JAK2 negative and mostly asymptomatic. By reviewing older blood tests we guess I’ve probably had it for around ten years but was definitely diagnosed with ET via a bone marrow biopsy three years ago.
It is this ten year mark that has me most concerned – reflected in my first question below.
- What studies have been conducted to measure healthy living on mortality for patients with ET? …
CH: The short answer is no-one has measured benefit of exercise, diet and lifestyle in ET patients. However there is a wealth of info out there for “healthy” folk. So I encourage everyone to take up the mantra of healthy lifestyle.
- What does the future hold for JAK2 negative patients in terms of new treatments?
CH: All new treatments (with possible exception of PEGASYS where there isn’t any detailed data) appear to benefit both JAK2 pos and neg patients.
- Does the untreated platelet count have any significance? Without treatment my platelets hit around 1800 – so extremely high. With my Anagrelide treatment I am keeping them down to around 600 – 700. (I was intolerant to hydroxyuria – killed off my red cells)
CH: Untreated platelet counts over 1500 increase the risk of hemorrhage.
.In Dr Mesa’s fantastic video outlining Essential Thrombocythemia on the web he mentions that medication does not stop the “progression” of the disease. It is this progression that interests me most – do we have a clear picture of that progression? What are the milestones of the progression? How do things progress from asymptomatic patients to symptomatic and what can we learn from that transition?
CH: These are questions we are trying to answer in long term clinical trials such as PT-1, the PEGASYS trials and trials with JAK inhibitors. Sadly we do not have good understanding of these events although we are learning more.
RS: There is no question that about 5% of the patients with ET will transform to myelofibrosis by 10 years, but the overwhelming majority of patients does not. Thrombotic risk may be complicated by associated medical diseases such as diabetes and hypertension. Notwithstanding the aforementioned, of the myeloproliferative disorders, ET has the best prognosis, I believe, agreed by all of us. I do think that exercise is good for everybody as is weight control. There is no systematic study of exercise in ET that I am aware of, but as the saying goes, “it can’t hurt.” I do not believe that allowing the platelet count to be allowed to rise untreated to 1,800,000 is prudent. I know there are differences of opinion regarding this. Your intolerance to hydroxurea, as I mentioned previously, is understated in the medical literature and “killing of your red cells” by hydrea is not uncommon.
Jakafi for PV…any alternatives?
30. Monique…The drug costs $8600 and with medicare part D, Incyte Cares will not deal with you. My itching is so beyond the pale, that I am beside myself. I get stabbing pain as well. Pegasys is not helping those symptoms. Medicare Part D won’t pick up enough of the cost. The clinical trials are double blind placebos which really doesn’t help me. Does anyone have suggestions for me?
SV: There are several ongoing trials with different JAK inhibitors for patients with PV and MF at our center (MD Anderson Cancer Center) in Houston, and medications are of course free for participants. Most studies are not blinded and placebo controlled. To make appointment with me (Dr. Verstovsek) one should call 713 563 2000.
What to do about aggressive mastocytosis?…
31. Shashanna Kocinski, Australia…
I am a 63 year old female who has had systemic masto (diagnosed) for 10 years. My spleen was removed in 1997 as it had grown too large and hard but the diagnosis of SM was not made then…I had a bone marrow biopsy 2 1/2 years ago. I have a serum tryptase level of 210, significant osteoporosis and extreme amounts of mast cells in the gut.
Two years ago my hematologist put me on Tasigna and that has made a difference in symptoms but has not lowered the serum tryptase level. I have habituated or accommodated to the gut problems but the bone pain and head aches are debilitating. My Doctor is not sure if it’s aggressive or not.And finally, the question: how do I determine if it is aggressive?Is tasigna the best treatment?
CH: There are standard criteria for assessing whether systemic mastocytosis (SM) is aggressive or not, nonetheless even patients with so-called indolent disease have marked symptoms. We have not yet identified the “best” treatment for SM; tasigna is one but there are also others too if this isn’t working for you.
SV: in general, aggressive means that the disease affects organ function, vs. indolent that does not. For example, if blood cell count is abnormal and one has low platelets or low red blood cells requiring transfusion, that means that bone morrow function is not normal and that patient has aggressive mastocytosis. Similar examples can be given for liver function, GI function (if patient loses significant weight due to malabsorption, etc…There is no “best therapy” for mastocytosis but there are several possibilities, including interferon, cladribine, prednisone…
Five year old with ET…
32. Jen Donohoe, Dublin….My 5yr old daughter was diagnosed with ET in April of this yr. i am totally in shock and devastated by this news. Also, the lack of information available on children with MPD’s. she is JAK positive, she had a bone marrow biopsy in April. She is currently on no medication. she is doing well apart from ‘cluster migraines’. i am very happy with my daughters hematologist, she seems to really know her stuff. at the same time from doing research online, people in the mpd community have urged me to seek an ‘mpd specialist’ for my daughter. i am wondering what your advice would be, since you’s are the specialists! Even though i am happy with my daughter’s doctor, i would hate to look back and regret not seeing a specialist…
CH: You seem to have an excellent relationship with your daughter’s hematologist which is really important. I would suggest you discuss this matter with her. She has probably discussed your daughter’s case with colleagues so in effect you already have an MPD specialist.
RL: There is little data on pediatric patients with MPNs, and even fewer experts on this rare subset. I would definitely seek out a specialist opinion, both to ensure her treatment is managed well and to keep posted on new diagnostic and therapeutic advances.
33. Patti Cooper, West Virginia… I was diagnosed with PV in 1988 at age 28. I had gone to a diet clinic which required lab work before starting their program and was told I needed to see my doctor immediately. The diagnosis of PV was confirmed through lab tests and a BMB which showed I was Philadelphia chromosome negative. I was treated by phlebotomy to bring my HCT down to 45 and continued with phlebotomy only for approximately 16 years…. In June of 2011, my platelet count started dropping, I started having night sweats, and the spleen continued to grow. In December of 2011, I entered a clinical trial for SAR302503 …. My platelets were 50,000 at the start of the trial… After several weeks, I experienced a reduction of the spleen to 19 cm and it was no longer across the midline. Wonderful relief!! However, my platelets dropped below 25,000 in cycle 3 and I had to go on a medicine hold, then re-started the meds at 100 mg. The spleen gradually grew back to 24 cm, my platelets dropped again and in June 2012, I had to be taken off the drug as my platelets did not show a consistent recovery. At that time, I was told that my BMB done in December 2011 showed “early myelofibrosis” and it was recommended that I have a splenectomy. I am not losing weight, am not in severe pain, and have fortunately not had any complications such as clots or bleeding. I sought a second opinion from another MPN expert and he is opposed to the splenectomy due to the poor outcome he has seen with some of his patients. He recommends Jakafi 15 mg once per day, keep a close eye on platelets and raise to 15 mg twice a day if platelets will allow….
So, I’ve taken all this information to my local hematologist who has followed me since diagnosis and he feels unqualified to be the “tie-breaking” vote between two of the top experts in the country. (neither is a part of this panel of experts) Splenectomy or Jakafi? I’m very afraid of the surgery after reading about some of the potential problems associated with the surgery itself, post-surgery complications…. However, I’m a music teacher, not a doctor and don’t know what risks I may be taking if I don’t have the surgery. My doctor is also not sure how to handle low platelets during treatment with Jakafi, so I’m somewhat concerned about how this would work. I have made myself sick trying to decide what to do. Please, can you help to sort through all of this and suggest the best way to proceed??….
CH: Patti your questions are excellent and there is clinical data which should help and perhaps also a thought that you can always try the drug then think of splenectomy but not the other way around. Two studies are underway using JAKAFI in patients with blood counts exactly like yours showing (so far) that it can be used safely and effectively. So on this basis I would use drug then consider op if needed. I am also thinking you should have a consult on SCT because it seems to me that your disease shows some features which would make me consider this option in the near future. You could consult on this while taking the JAKAFI.
SV: Jakafi is a pill that is taken twice a day, not once a day. In patients with low platelets count the starting dose should be low, to offset a risk of lowering platelets and requiring platelet transfusion. Therefore, since your platelets are low at 60, one may start with 5mg twice a day for the first month, then dose is increased to 10mg twice a day during second month, if there is no major benefit and no significant decrease in platelets, and then increased to 15mg twice a day for the third month, again only if there is no benefit and no significant lowering of platelets. Hope this will help. It is much safer to take pills than undergo surgery of course
ET to Mt. Everest Base Camp…
34. Colleen Rudnisky… I am a 52 year old female diagnosed with ET two years ago. My blood work is very consistant with my platelets being in the 800 range. I take no medication. I quit taking aspirin because of nosebleeds( several a day)I am in good health!
I am planning a 19 day trek to the Base Camp of Mt Everest and was wondering if I should be aware of any limitations because of my high platelets. I will be accending at a slow pace to 18,000 feet. Two years ago I did hike to 14,000 with no trouble. I took Diamox to help with altitude sickness. The tour company is aware of the dangers of altitude sickness and have a slow and steady pace set out for us with several acclimitasation days en route.
Is there added danger because of high platelets? Is Diamox a good option to help prevent altitude sickness? Any input you give would be greatly appreciated. My hem is on holidays at the moment.
CH:Any advice needs to be premised on knowledge of all your medical history, based on what you have said – completely fit and assuming no bleeding or clotting. Then this seems fine. Please make expedition leaders and insurance companies aware of your condition too however.
SV: Diamox is good to take, yes. There is no correlation between platelet number in blood and risk of clotting, so you are fine with that too
RM: Patients with MPNs have been successfully able to pursue a variety of very active sporting activities including significant endurance events, long distance cycling events and being at a high altitude. Factors that weigh in on the safety for these individuals depend upon their other illnesses, what difficulties the MPN has had on them in the past and how well controlled they are. In theory, a high platelet count alone in an individual who is being appropriately managed would not necessarily be a contraindication for being at high altitude, potentially even the Everest Base Camp; however, that final decision really is best left to your treating physician who knows the full situation regarding your health, the symptoms that you have with the disease, the symptoms and issues you have had with your illness and your current therapy. I would say in the ideal world, a normalized platelet count for such an activity would probably be best, but again that specific recommendation comes best from your physician.
MPNs and lymphoid malignancies….
35. Karen Letts…I was diagnosed with ET in 2010. My question is:
My family history has Hodgkin’s Lymphoma in it. My maternal grandmother and her sister both had Hodgkin’s. My maternal aunt was diagnosed with “too many red blood cells” (PV?) and maternal uncle died from Leukemia. I have the JAK2 mutation. Has there been any link made between Hodgkin’s and MPNs?
CH: There is a known link (but rare) between lymphoid disorders such as Hodgkin’s disease and MPD.
SV: in patients with myeloproliferative neoplasm, there is increased incidence of lymphoid malignancies, like lymphoma. This is well established. Link between lymphoma in family members of a patient with PV, ET, or MF have not been established.
RS: There is an increased incidence of other malignancies in patients with myeloproliferative disorders. The association has recently been reported in Blood. We have seen non-Hodgkin’s disease and Hodgkin’s disease in patients’ myeloproliferative disorders.
AO: JAK2 involving rearrangements [e.g., t(4;9)(q21;p24)] have been recently found in cases of classical Hodgkin lymphoma but no JAK2 mutation is documented in this condition. Familiar MPNs are usually JAK2 negative. To my knowledge, no evidence for a link has been established so far
Asymptomatic with high blasts…treatment?
36. Jaswinder Singh….This is medical oncologist – 70 yr old with dx of cmml1 – normal cytogenetics and now low grade cytopenias. Asymptomatic has increased blasts to 24 percent. Is it unreasonable to treat with dacogen ?
SV: Very reasonable
RS: Clinically, it is unusual for someone to have 24% blast in the peripheral blood and also to be asymptomatic. Personally, I would treat this patient with chemotherapy.
RM: Answer: If I read the question correctly, it appears it is regarding transformation to CML blast phase. CML blast phase, if it is BCR-ABL mutated, is a very challenging scenario; in particular, in an individual who is 70 years of age. There are several questions that would need to be done in the setting of a comprehensive consultation with a hematology team as to whether an eventual bone marrow transplant would be a consideration. Age alone would not preclude that, but on the basis of age response to the acute leukemia to other therapy, availability of a donor and the patient’s wishes would all factor in to such a decision. There are medical treatments that have activity, potentially the tyrosine kinase inhibitors, but this would depend upon what the history had been prior to the development of CML blast phase. There has been activity and experimental trials with a new medication, ponatinib, or one would be able to treat it with our other non-induction chemotherapy regimens such as hypomethylation therapy, decitabine or azacitidine. Again, a very complex situation that really requires an entire team looking at the spectrum of options from available therapies, clinical trials and bone marrow transplant to come up with the best issue
Hydrea and low sodium?…
37. Freddie Rosenfield…I have myelofibrosis and my internist has diagnosed SIADH/hyponatremia. I charted hydrea use and it seems to correlate with the low blood and urine sodium values.
Has this been noted in other patients? If yes, is there a standard treatment? I’ve tried water restriction which didn’t help.
CH: I am not aware of this link. I would expect a thorough work up to look for other causes of low sodium which should then guide treatments.
SV: I am not aware of the connection between hydrea and SIADH. Would follow instructions from your doctor on how to treat SIADH.
Spleen and ruxo?…
38. Cheryl Boyd….I was diagnosed with primary myelofibrosis in1981. I have been on differing doses of HU for 20 years. I am also Jak-. I have been on radiation treatments twice in the last 4 years to reduce the size of the spleen. I had 5 treatments of radiation in May, but my WBC and RBC went to zero and my platelets to 35. My oncologist does not think Ruxo would benefit me since I am negative. What are your thoughts on what options I might have? My spleen is huge and I take 500 of HU 3 days a week. My WBC is now 1.5 and my RBC is 3 and platelets 191. …
CH: Ruxolitinib or JAKAFI works for patients regardless of whether the have the JAK2 mutation or not; based on what you have said I would consider this treatment but there may be other factors which may be affecting your doctors decision.
SV: Ruxolitinib is JAK inhibitor (not JAK2 mutation inhibitor) and benefits patients with and without JAK2 mutation to the same extent, there is no difference. According to your counts, you are excellent candidate for ruxolitinib
PV keeps progressing….
39. Dave, Florida My PV just keeps progressing. I started out with phlebotomies, and am now on 1,000 mg Hydrea per day. I am tired of taking Chemo. Does the disease just keep progressing until death? ( I realize it can turn into another MPN at any time)
SV: No. Disease can be effectively controlled with hydrea, interferon or new medications in development and people live normal life
RS: The myeloproliferative disease group (MPD-RC) does have a protocol regarding the use of interferon in patients resistant to hydroxurea which you certainly seem to be eligible. I suggest you contact one of the physicians in the MPD group. You will obtain Peg-INF without charge.
Pregnant with an MPN…
40. Jennifer Olsen…Hi! I am a newly diagnosed 38 year old female. Coincidentally, just as being diagnosed I found out I was pregnant. I understand that I am a rare bird and there isn’t a doctor on my great team that has treated someone that like me. With that said, I’ve been relying on others opinions and what outdated info I can find on the internet to answer my questions. (thanks for being here to also ask!)
The two things weighing most on my mind right now are….
1) as I approach my due date (1/1/13) by OBGYN feels I need to be induced at least a week early, I would love to hear your thoughts on that. (I delivered 11/1/04 and 5/1/09 both healthy girls w/normal delivery).
2) is there any information out there that would solidify an answer as to whether we should pay to privately bank the babies cordblood vs. donating it? would it benefit me in any way?
CH: Congratulations. In our center we would not induce patients with MPN and pregnancy as long as prior pregnancies have been OK and the patient is healthy. I generally advise against banking cord blood specifically for MPN since we rarely do cord transplants and you are probably unlikely to need one for many many years at which point we cannot be certain about how useful the cord blood would be.
SV: What is the diagnosis?
Breast cancer, lymph node biopsy with PV?….
41. Kristy Nordaas…. My mom was diagnosed with polycythemia vera several years ago, and has treated it with phlebotomies, hydrea, & aspirin. Now she has Stage 0 DCIS breast cancer. I’ve seen that often it is recommended to do a lymph nodes biopsy with breast cancer surgeries. Her surgeon and oncologist do not know much about PV, so we have not gotten clear answers on whether or not to mess with the lymph nodes. My aunt has the same 2 diseases, but was diagnosed with PV after her breast cancer surgery. She had a lymph node biopsy, so now she has to do her phlebotomies from her hand, which is painful.
Another concern for my mom, is that since her PV diagnosis, she has gotten pneumonia, shingles, and bronchitis (multiple times). So it seems that her immune system is not as strong as it used to be. What will be the effect on her immune system if lymph nodes are disturbed. I realize that it’s important to check for the spread of cancer, but just wondering about weighing the options.
SV: Breast cancer is very serious condition and I would strongly suggest that all recommendations/suggestions by treating doctor be followed, including lymph node issue. PV is bystander that can be effectively controlled with measures already in place, and should not interfere with attention to breast cancer.
RM: In an individual who has the need for a breast biopsy or a lymph node biopsy in the setting of breast cancer, P vera should not be a limiting factor to undergoing the appropriate diagnostic and therapeutic plan for breast cancer. If an individual has uncontrolled PV, the physician may choose to try to rapidly normalize counts prior to an invasive procedure with phlebotomy or other anticoagulation if appropriate in the individual setting. That being said, the urgency of an accurate diagnosis and plan in the individual with breast cancer is tantamount and will try to make the best of the PV risk while undergoing that necessary medical intervention
Iron intake and PV?….
42. Peggy Frederick, Nutley NJ… Since primary PVers are overproducing red blood cells, our iron intake is closely monitored via ferritin levels. Many of us are extremely diligent about cutting down or eliminating red meats from our diet to reduce our intake of heme iron. We also watch how we ingest non-heme forms of iron particularly with regard to consuming it in concert with Vitamin C because we know that the combination will enhance the ability of iron to be absorbed. Are we proceeding wisely in this regard? If not, how would you recommend we adjust our nutritional intake via diet and supplements. Are there any food sources or supplements we should reduce or eliminate given our high red blood counts? Thank you
RM: Iron itself is not a stimulus for a P vera, nor is it harmful. The challenge is that when individuals are on phlebotomy alone, phlebotomies primarily work in controlling the hematocrit in patients with P vera by inducing iron deficiency. So, in these individuals, if we give them oral iron, it would just stimulate more red cells to be created and more phlebotomies need to be undertaken. This is primarily in the issues of iron supplementation and iron vitamins. The amount of iron in food, even red meat or other rich sources of iron, is still relatively modest compared to iron supplementation, so in general, I have not found that it is necessary to be overly restrictive with iron in the diet and instead just focus on individuals who are dependent upon phlebotomy alone that we try to avoid specific iron supplements that are working contrary to the goals of the phlebotomy.
Kidney disease with PV….?
43. Jeannete Sense… Background: I’ve been a patient of my local Hematologist for 5 years, taking Hydroxyurea for a “classic” case of Polycythemia Vera. From 1989-1993 I received treatment for Minimal Lesion Disease from a local Nephrologist. I failed a year trial of prednisone and became stabilized on a year of (100 daily) cytoxin.
My kidney functioning has been declining…. What should be my focus, as I want as little intervention possible (hence the referral to the nephrologist to do the CT scan if he feels it necessary–instead of each doctor doing their own tests).
SV: The two problems should be dealt with separately and in parallel. PV apparently is treated properly with phlebotomy, aspirin and hydrea; that should not be changed. Kidney problem is under care of kidney specialist, which is fine too.
On Pegasys…with side effects.
45, Tom Weissbach…I am now in my fourth week of Pegasys at 45mg. I have an enlarged spleen 21cm and liver 19cm. My only side effect has been severe gastro discomfort with no appetite and weight loss. I have had problems like this my whole adult life, just not this severe with weight loss. I just received my old colonoscopy/endoscopy report from late 2006 and it shows gastritis and colitis with non specific chronic inflammation. I know one of the side effects of Pegasys is exacerbation of auto immune disease and colitis. Do you have any suggestions for dealing with this side effect? I really would like to continue with the Pegasys.
CH: I would look at what factors seem to spark the discomfort keep a diary including food and drink; think about dose of pegasys and discuss with your hematologist all these things and whether starting a lower dose and building up might help.
SV: 45mcg is very low dose and unfortunately, if this dose causes problems, the usual approach is to discontinue it. I am sorry.
When is phlebotomy needed?
46. Susan Kennedy, Lexington KY I have recently read that there are different opinions about when a phlebotomy is needed. The guidelines seem to be more flexible than in the past. What are some of these latest guidelines and do all countries agree on the same ones?
CH: Most countries use 0.45 as a target; some recommend a lower target if the patient is symptomatic at 0,45.
RS: We are very liberal with the use of phlebotomies. In our own practice, we believe the hematocrit should not exceed 45% in men and 42% in women. Our attention to this detail has made our thrombotic risk virtually zero compared to other studies recorded in other literature. Blood is a non-Newtonian fluid. By that I mean, viscosity increases logarithmically as the hematocrit rises. Increases in HCT over 45 causes significant increase in viscosity. Therefore, the hematocrit is of significant importance with respect to thrombotic risk in my opinion. Having said that, we do know the hematocrit level is not the only issue regarding tendency towards thrombosis in PV. Certainly, platelet, white count and other vascular factors play a role. However, controlling hematocrit is such an easy maneuver with phlebotomy, I see no reason in not paying strict attention to this detail. Our clinical results substantiate this fact.
Monthly phlebotomies increase blood counts?
47, Sheridan Emery, Clayton California…66 years old, diagnosed with PV three years ago, JAK2 negative. 8 weeks of weekly phlebotomies @500cc each. Then every 3-4 months, now, in last 1.5 yrs. – bi-monthly – consistently with Hem between 15-17 and HCT 45-47; platelets between mid-to high 400’s except last July and again this July, 2012 – slightly over 500 mark. I am now seeing a new Hematologist, Dr. Esther Q. Catalya at Mt. Diablo Oncology and Hematology Center and she has “suggested” 250cc draws – monthly, as needed. She allowed me to go 2 months this May/June and I had a 500 cc draw July 11, 2012 which has left me wiped out and very pale – not so unusual, but I’m wondering if she might just be right! Less stress…..with less withdrawal – makes sense? BUT, my concern is having such frequent Phlebotomy Treatments – does this just exacerbate the renewal of new/more cells…..? Also, now being watched/tested for hypercalcemia. Would appreciate any comments.
CH:I would monitor you symptoms and try to correlate these with the size of phlebotomies I think the approach is reasonable I have used this for several patients myself. I would not be concerned about monthly phlebotomies increasing blood counts. The hypercalcaemia needs to be investigatd it is not likely to relate to your PV.
48. Patricia Harrison… Hello, I’m a 59 yr old lady who has had E-mail correspondence over the last year with Dr. Mesa, who has been wonderful. My question is:
I have just had #50, Venofir iron infusions over the last 4 years. I was told that because my RBC’s are so immature , they die off before the iron has anything to adhere too? Is this always going to happen to me? And am I just a complex case , as Dr. Mesa calls me? My counts dropped and my ferritin also dumped to about 4, so just walking across the room was almost too much. I was taken off my Hu for a month and given 2 infusions, which made me feel human again, and now counts have re-bounded, and started the 500 mg Hu daily again.
CH: Things are clearly very complex for you just as Prof Mesa says. It is impossible really to answer your question without a thorough face to face review of your case and all results. I am sorry
Jakafi, heart disease, and jet fuel…
49. Mike Masello Boston… My name is Michael,I am 50yrs old father of 4 children…I have 20 yrs in the transportation industry. I was born in Boston Ma. and grew up right next door to Logan International Airport. There is a reason why I need to let You know where I grew up.I lost my dad(also 30yrs in transportation industry) to acute leukemia when he was 58yrs. old,he also grew up in the same area as did his parents, both died from bowel cancer, both where late 70,s.I was diagnosed with Myelofibrosis and the JAK2 mutation through a bone marrow biopsy in 2005. …and I have been on Jakafi 20mgs 2x a day since march 27 2012. Since my last visit approx 4wks ago, my blood counts where good spleen reduced 20% still have bone pain some fatigue, night sweats but not as frequent and have been going through EMG testing( having pain,cramps,weakness in legs & back pain) ….I started feeling extreme tightness in right arm and chest roughly 8-10 times in the past 45days and Im getting frequent severe headachs very strange feelings.
I have a couple of questions: 1-Do MPNs cause heart disease? 2-What does JAKAFI cause? 3-Living near jet fuel,diesel fuel and other carcinogens have a major role in the breeding of MPNs and gene mutations? 4- and what can be done to stop it?.
SV: 1. No, these is separate issue in your case. 2. Jakafi may lower blood count too much in some patients; it does not cause heart problems, blood pressure issues, or any of the problems you mentioned. 3. This is presumed, yes. 4. Follow your doctor’s recommendation, you are in good hands
After SCT, how long before RBC and HG normal…?
51. Jen Speyer… How long does it typically take for RBC and HGB to get back to normal after a Allogenic Stem Cell Transplant. Platelets and WBC are going up nicely. I’m currently at day 130.
CH: This is very variable depending on donor and recipient factors and complications like infections etc.
RL: It can take up to a year for counts and marrow changes to normalize after a bone marrow transplant.
RM: The response to a stem cell transplant in MPNs, particularly in myelofibrosis can be delayed where we see that it can take up to a year for individuals to see resolution of the enlargement of the spleen and improvement in fibrosis. The anemia of myelofibrosis can be slow to respond post-transplantation because aspects of healing from the transplant can also lead to anemia from the other medications, from chronic graft vs. host disease and even from delayed engraftment from the donor marrow. I would say that this amount of time in terms of needing transfusion, it would not be uncommon that this could certainly extend into several months or even a year. There are some individuals that have successful stem cell transplantation who never fully return to a normal hemoglobin.
On second opinions….
52. Vicki Bazin, Victoria, Can….I would like to know how important it is to get another opinion when dealing with MPNs.
I have e/t which was diagnosed at age 47 I am now 51. I am concerned about my e/t moving to mylofibrosis. I understand there has been some information that perhaps e/t is early stages of m/f.
I was tested for JAK 2 in 2007 when I was diagnosed which was negative but after I received my 23 & me results they suggest that I have substantially increased odds of developing JAK 2.
I am really not to sure what all of this means. I spoke to my haematologist about this but he really did not say to much at all. My G/P told me that I really would not get any different information so I should not bother seeing someone else.
CH: Vicki whether you have the JAK mutation or not does not effect the likely course of your disease and it is rare for patients to go from being negative to positive. If you have concerns which aren’t being addressed you could consider a second opinion.
Menopause and ETand BMB timing…?
53. Aileen Shaw, Northeast England…I was diagnosed with Essential thrombocythemia November 2010 and am Jak2 positive. It would seem that treatment is quite different here in England. My platelet count is 750,000 and stable at the moment and I take aspirin every day. I notice from contact with others in USA that it is routine to have a bone marrow biopsy taken but was told this was not necessary, is this correct. I would also like to know if ET is a form of blood cancer as I was told that it definitely wasn’t yet have seen on websites that it is so am quite confused. For the past year have also suffered from recurrent UTI infections and have been a Urology patient since last July and have been taking antibiotics every day for past 3 months and have another 4 months to continue until I return to Urology in October. A cystoscopy last September showed no abnormalities and was wondering if I’m just unlucky or if this is a common problem with ET. I am constantly exhausted and have night sweats but this has been put down to the menopause ,is this likely.
CH: In the UK national guidelines do not mandate a BM biopsy for the diagnosis of ET provided certain criteria are met. If you are concerned about a possible mistaken diagnosis I would discuss with your hematologist. The symptoms you describe do occur with the menopause and ET so tricky question to answer are you definitely menopausal?
54. Helen, Sussex, England…I have ET, well controlled with Anagrelide, and I should like to know what triggered the peripheral neuropathy I have in my feet now. Plavix hasn’t helped much so is there any other treatment or research into this.
CH: Peripheral neuropathy has many causes including drugs but also diabetes, vitamin deficiency etc.; Helen this really needs a thorough medical work up I am afraid.
SCT — Decision
55. Sue_Waite Cleveland…. am 42 years old, diagnosed with MF in February of this year. I went to the doctor, after many years, because I was feeling exhausted and had a lot of side pain. I was pretty overwhelmed at the diagnosis. My doctor was going to start me on Jakafi, but then in the last month I have been feeling great and we decided to hold off on doing any kind of meds or treatments. My counts are almost normal and my spleen was 10 cm and has shrunk to 6 and my energy is great. He believes my spleen shrunk because I had read in Jakafi info that if you were of child bearing age you had to be on some kind of birth control, so on my own, I had it prescribed. Since it increases clotting risks, my hem/onc had me stop taking it.
We have started discussing the possibility of a BMT. Deciding the right time to do it is overwhelming me. My dr. says I have to do it when I am strong enough to beat it, but also have to weigh the risks of taking on a whole other host of problems that come with it knowing I could live well with MF for a very long time. Plus, there seems to be a lot of hope in the advancement of MF treatments.
I would like another doctor’s opinion on when it is the right time to have a BM
CH: Sue this is a big decision for you and your family it needs careful review of your disease the risk factors you have and what type of BM donor you might have all of these things impact upon decision making.
SV: Unfortunately there is no clear answer to this question. Approach to therapy (including bone marrow transplant) is individualized and depends on disease characteristics, trends in a change for worse, patients other medical problems and age, personal beliefs, etc
RM: This is a very important but very complex question that we struggle with each day as a field and we struggle with each individual patient that we visit with. There are many factors that we look at and the factors involved have a big impact on what is the right timing. First, the donor. Is there an appropriate donor? Is it a safe donor? The less safe the donor, the less the enthusiasm for a transplant. Next, what is the risk with the myelofibrosis? How problematic is it? How likely is it to be life threatening within the next one year, two years, five years? Typically, we think that individuals who we think are expected to live well beyond five years, a young asymptomatic myelofibrosis, the risk of undergoing a bone marrow transplant may be excessive for the risk of the disease. Next, we look at the health of the patient. First, their risk with the myelofibrosis – how life threatening is it; secondly, what are their other illnesses, and then finally the age of the patient; additionally, clearly the philosophical goals of the patient in terms of how aggressive they wish to be with their disease. All of these are important factors in determining the appropriate timing for an individual and need to be considered.
How often should BMB be done?
56. Gwendolyn Wall, Hi I have ET taking plavix, hydrea and pravastatin. I was diagnosed back in 2002. My question is How often should I have a bmb done or is it unnecessary only at diagnosis
CH: Strictly speaking a BMB is only needed at diagnosis or if the disease shows signs of progression.
SV: Bone marrow is usually repeated only if there is a significant change in blood count, and one suspects change in disease characteristics and therefore would repeat biopsy to address that possibility
Extramedullary hematopoiesis and nuclear bone scan…
57, Peggy Reeve Does a nuclear bone scan show extramedullary hematopoiesis? I am having one soon and hoping it will show all the bone pain I am having which I imagine is hyperactivity
CH: Sometimes a bone scan can detect this abnormality but other tests may be needed too.
RL: This test will not show EMH in all cases. The diagnosis is more clinical than radiographic, though a MRI of a specific bone with pain can see EMH.
Physician: Patient consult…
58. Dr. Anthony Ruggeri … I have a 52 yo man who presented in oct 2010 with night sweats and fevers to his PCP, CBC and CMP were drawn which were significant for platelet count of 627,000
Bone marrow biopsy revealed hypercellular marrow megakarryocytic hyperplasia and increased reticulum fibrosis normal male cytogenetics, peripheral blood negative for JAK 2. Pt was placed on aspirin and observed by December night sweats were so bothersome it was interfering with his ability to work due to fatigue the following day. His platelets had increased to 900,000. I then started Hydrea 500mg every other day. Pt had complete resolution of night sweats and platelets have hovered in 600-700,000k. Pt feels good. PS=0 Pt did undergo imaging of c/a/p to look for other causes of night sweats only Abnl was liver hemangioma no splenomegaly or LAD.
My question is would you advise any change in management any role for transplant, currently only other lab Abnl. Is mildly elevated LDH 291 (nl=234) WBC =6.8 hgb=13.7 plt=638.
SV: Management appears excellent. Would not suggest any change or transplant
AO: The reported presence of marrow fibrosis (degree unspecified) in conjunction with the presence of marrow hypercellularity and elevated LDH might suggest the possibility of very early PMF. You might want to consider repeating a bone marrow biopsy to precisely assess the current marrow status (e.g., cellularity, degree of fibrosis and megakaryocytic atypia). The marrow findings might be helpful in determining the need for management changes, e.g., starting peginterferon alfa-2a. The latter has been found useful in stabilizing the disease by preventing further myelofibrotic progression [Silver RT, et al. Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report. Blood. 2011;117:6669-72].
Anemia and HU…?
60.Gilliam Beamish…on my last visit to my hematologist he said he was worried that my hemoglobin has dropped to 10.4, he said if it drops by 1 on my next visit which will be in 8 weeks he will have to consider a different medication. what would be the best meds for me to take i am taking 500mg HU daily and 1000mg on sundays which has just been increased by one extra due to my platelets rising over 8 weeks from 220 to 406. i would appreciate as much advice as possible so i can feel informed by my next visit
CH: Gillian it is important to check for other causes of anemia eg iron deficiency and balance out treatment benefit with side effects. This will depend then if other causes have been excluded on whether you have symptoms of anemia (like tiredness for example) and how well controlled your blood count needs to be.
What does Jakafi do?
61. Dean Finch… I am fortunate to be able to take… Jakafi (5 mg twice daily). My first question is … could provide an understandable explanation of what this drug really does? I know my spleen is decreasing in size, however, my blood counts are still low and I am currently on weekly Procrit injections (50,000 units) to manage my low hemoglobin. My second question is will this drug eventually permit my bone marrow to produce healthy red blood cells so I won’t need the Procrit any longer?
CH: The drug is a JAK1 and 2 inhibitor as such it will sometimes worsen anemia, in some patients anemia has improved. In clinical trials this generally stabilized by week 12. There is experience of using procrit and the JAK inhibitor. Clinical trials show that this drug reduces the size of spleens and improves quality of life possibly improving survival.
SV: The drug inhibits the growth of cells and therefore reduces spleen and liver size, if they are enlarged, and provides anti-inflamatory effect and therefore controls systemic symptoms like fatigue, bone aches, sweating, etc. it is unlikely to increase red blood cell count. Typically patients are on little higher dose, 10mg twice a day or more.
– MPNclinic Project Coordinator: Mary Morochnick, R.N.
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Comments on: "MPNclinic Special Section — October 15, 2012" (5)
This is so helpful you have no idea. As a friend and caregiver to a PV patient who has had horrendous care( never a BMB, unbelievable HU side effects that no one has addressed in 10 years) this has been great. Thanks all
Thanks to the panel of experts for taking the time to answer questions. Also thanks to those who have asked the questions. Some I never thought of asking and find the answers helpful. And most of all thanks to Zhen for publishing them.
I thank each and every one of you for your most valuable input on our MPN’s and will look forward to next month’s MPNClinic report.
Hi, Mariel… Sorry. I can sense your frustration and despair. It might help to clarify how MPNclinic works. Questions are logged in as they arrive , aggregated, and sent as a group to the physicians on the panel for response. The results are published each month,with individual responses sent to patients as we receive them.
Two groups of questions have been sent to the Panel. We thought each doctor would answer a few questions however some of the doctors feel compelled to answer many questions which is far more generous than we anticipated. In fact, all 61 questions in the first two groups have been answered. Your question on managing both MPN and Porphyia is #68 and in the third flight of questions. Hopefully you will have a response. Meantime, I’m glad you have a good relationship with your docs at Mayo.
It’s great to get information this way. Thank you! No one answered my question either this time or last time we had a forum here. I don’t expect anyone has ANY idea how you manage a person who has both PV and Porphyria (HCP porphyria). I was unable to take any chemos (tried Interferon, Pegasys, HU and Angrelide) but had success with p32 last spring. I will probably have to take p32 again, but my platelets, which did go down under 400,000, have been rattling around in the 635 range for a month. I was wondering if I should have a blood aggregation test–would have to go to UNM–to see if I need to take p32. I have not had a stroke or clot, but I did have a nosebleed for the first time two weeks ago, associated with very high blood pressure (my pressure is usually low normal, and the attack may have been a porphyria attack). My worst symptoms are very painful feet and jerking/spasm of hip and legs if I don’t take enough magnesium. the night I had the nosebleed I couldn’t seem to get control with magnesium, so I was in stress. Anyway, I have met only two other people in the world (on the internet) who have both PV and Porphyria. Some specialists have seen no one who has both, they claim, and know practically nothing about porphyria, which is, to put it mildly, a darn shame.
I learned to almost totally manage my porphyria, not diagnosed until I was over 60 through medical ignorance. But with both PV and Porph, the battle is ongoing. I don’t expect anyone can answer my question but I believe it is important to keep putting it out there, because people with porphyria are the very bottom of the barrel in the medical knowledge area. Thanks for answering questions of others so well. My oncoologist at Mayo is Dr. Cammoriano (I like him a lot) and my radiation oncologist is Dr. William Wong (he talks very little but thinks very well).