I received my first MPN diagnosis about 7 weeks ago: PMF, stage 2, calreticulin positive (52-bp deletion mutant) without other somatic mutations. Initial platelet levels of 950-1200 (prior to Dx) were not reduced significantly by taking 500 mg HU/day, so nearly 2 weeks ago that was increased to 1 g/day. Spleen has probably increased in size in past two months, as it now provides a little pain when I climb hills for >30 minutes (when I force myself to get out, as fatigue is bad). First spleen measurement ever, via ultrasound, was made 3 days ago: ~500 cc. I'll do another CBC on Saturday and talk to oncologist on Monday. If platelets levels are not lowered, how much increase in HU can I endure? I have had some itchy rash in response to HU apparently, but I can handle it, as it's nothing compared to the fatigue and pain. By the way, I'm 77 yr old male.
What is the maximum safe dose of hydroxyurea/hyd... - MPN Voice
What is the maximum safe dose of hydroxyurea/hydroxycarbamide?
A typical max I've seen here is ~2000, with 1500 max more common for ongoing doses from posts here. I was on 1000 for about 5 months. But each of us can have very different tolerance for different doses so you will want to watch for any severe effects as the dose increases.
Are your other CBC results ok? We can have a trade off where controlling one blood count makes a different count too low for example, this is part of the tolerance. So your Dr should spend time discussing your best dose and the reason for it.
Did they also give you your spleen size and weight? I think this is often part of the Dx. I got only the size in my ultrasound.
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Your CALR is sometimes referred to as "Type 1". In this recent interview with an MPN expert:
<<CALR type 1 mutated is more favorable>>. It is also more common from what I've read:
targetedonc.com/view/mesa-c...
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Has your Dr discussed Jakafi? (Rux) It's called a "Jak" inhibitor, but according to this report it seems to be relevant to CALR as well. It is known to be able to reduce spleen and improve symptoms. I'm not suggesting this, but only maybe to discuss with your Dr if it has not already come up.
ncbi.nlm.nih.gov/pmc/articl...
<<The effect of JAK inhibition with RUX in MF does not appear to be affected by the underlying driver mutation. ...the COMFORT-II study showed no difference in the response of CALR mutant patients in comparison to the cohort as a whole>>
I really appreciate your detailed response, EPguy. Good to know that I can go up in dose - probably without major problems. Yes, I know CALR, Type 1, has a more favorable prognosis, although I'm pretty surprised that I ended up with PMF as my first Dx. While my Hb and hematocrit are a bit low by normal standards, they are high enough that I can stand a bit of a hit. Since HU (and the JAK2 inhibitors as well) will bring down my Hb along with platelets, assuming HU works, I will need some cushion. I guess it is possible to get EPO or something else to pump up the erythrocytes somewhat as I undoubtedly will become anemic. Right now, I'm OK with staying on HU just to get the platelets more under control and to reduce spleen size. Reading the recent medical science literature indicates that more than half of patients taking Jakafi/Jakavi have to stop within 2-3 years, so I don't necessarily want to get started on it really early. True, CALR Type 1-positive patients generally benefit from the JAK2 inhibitors too, but their allele burden is not improved at all, unlike some patients with the JAK2 V617F mutation.
Right now, besides lowering platelets and spleen size, I would like to improve quality of life. In my case that mostly means less fatigue and less pain. Those are driven by the cytokines, especially interleukin-1β for the sleep-inducing fatigue. Unfortunately, I'm off NSAIDS due to the dangers of taking these at this stage of PMF. I'm not yet convinced that the interferons will be so useful for me. I'm holding my breath for the success of bomedemstat or similar, as I like the target chosen for that drug.
As Hunter says here you will need to monitor dosing closely with your specialist.
We all learn from each other, I was not aware of the diff in allele response on Jaki for CALR vs Jak2. In general the allele responses on INF seem to be superior and deeper. But as you say there is lots more to our goals than a single parameter.
I have seen the same regarding Rux effective period for MF. It seems to be more durable with PV, as My Dr also says. Maybe because there are fewer troubles with anemia in PV?
Have you and Dr discussed Momelotinib for future options re anemia? It's still in Phase 3 trials but seems to improve anemia:
<< anemia appears to be the leading cause of ruxolitinib discontinuation in MF patients>>... <<the odds of momelotinib-treated patients remaining transfusion-independent were 9.3 times higher (P < 0.0001) as compared to ruxolitinib-treated patients>>
jhoonline.biomedcentral.com...
I did see some of the results reported on the Phase 3 trial for Momelotinib that looked promising wrt anemia. I certainly have that in mind. I have not really talked with my oncologist in detail about treatment other than him acknowledging the possibility of using a Jak inhibitor if HU doesn't work out. It is such a shame that everything gets to be so incredibly expensive once you get past HU. Yes, I know, it's about 4-5X less expensive in Europe, and we can often get others (e.g., Medicare) to pick up some of the bills. Still, I'm not happy with sticking my fellow taxpayers with such bills either.
You are 77 years old. You have been paying others bills your entire life. Don't worry about medicare helping you out now. Sometimes the manufacturers have programs to help with costs and there are foundations that can help if you qualify. I don't understand how drug companies can expect patients to afford their medications for some drugs. The retail cost of besremi (the new drug for PV, which I have) is 180K per year. I don't know what the medicare cost for besremi or jakafi or the other new drugs are currently. Best.
Jakafi price is $16,984 for a 30 day supply of 10mg tabs(60) which is $203,000 a year, this is totally ridiculous.
In addition to ridiculous, it is also immoral and obscene that many people who need these drugs cannot afford them. Write to your senators, they are considering a bill right now that would limit the out of pocket costs for drugs for medicare beneficiaries to 2000.00 per year, they need to hear from us. I sent mine. Best to you.
I see your likely trouble with interleukin-1β. I've been taking bio available Curcumin and NAC supplements, with Dr consult, as are others here. These are reported to be active against interleukin-1β among other things. I think it is helping me reduce misery but of course no proof. Have you tried or considered any supplements?
Thanks for the suggestion of supplements. I need to look into that, as I don't really know much about them. By the way, what is NAC? N-acetylcholine?
N-Acetylcysteine. It's been studied for MPNs, in mice with good results and empirically in humans. There is a phase 1-2 dosing trial going on now. I'm taking much lower doses than the trial.
clinicaltrials.icts.uci.edu...
HU dosing is weight-dependent for ET. The dosing recommendation for HU for ET is:
*thrombocythemia, essential
[15 mg/kg/dose PO qd]
Info: titrate to control platelets and maintain WBC count
online.epocrates.com/drugs/...
Here is a bit more information on HU that you may find helpful.
drugs.com/monograph/hydroxy...
rxoutreach.org/monograph/hy...
oralchemoedsheets.com/sheet...
You will note the phrase "low therapeutic index." This means something specific.
Narrow therapeutic index drugs are drugs where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity.
fda.gov/industry/generic-dr....
The best course of action is to consult with a MPN Specialist who is familiar with dosing and managing the risks of HU. This provider can discuss how to best manage HU in your case.
Thank you very much for the information, Hunter. I'll check further on your links.
Hi welcome, daunting news isn’t it. I started on 500 hu a day. 17x 500 wasn’t enough so eventually 9 anagrelide a week was added. Some people are on 4x500 a day some people are on more than that. it’s all about your tolerance and full blood count numbers. You will be monitored closely and hu will be increased slowly until your correct dose for you is found.Good luck
OK, so you've had quite a bit of experience -- and going to higher doses. Sounds like you've just titrated to a level with which you can deal. Good to know, Wyebird. I appreciate your response.
I was on 2500 a day but stopped working so I have now been changed to Anagralide which has been up and down will see if it works any better. I have a BMB booked for 2 weeks as my haemotoligist thinks I may be shown signs of myelofibrosis at present I have ET with Jak2 positive hope you get sorted take care
Very sorry to hear of your diagnosis. The only thing I might add is that I have read that starting Jakafi early leads to a better long term course. It would be best to discuss that with your mpn specialist. Best to you going forward.
Hydroxyurea: how long it takes to reduce platelet level?
Hydroxy or Interferon for ET Jak2?
Hydroxycarbamide Dose 
Hydroxycarbomide
