As promised here are some plots showing two counts while off IFN therapy for 3 months. Leuk were also rising nicely. I stopped Besremi at the red line, mid Jan 2023. Last dose was reduced size since I already felt off. That is the one I passed out from.
At the January time my allele was at 8%, down from 14% 11 months prior.
The top green line for PLT is the standard 450 cutoff. PLT is high but in standard range. HCT is stable at just under 45 and in fact absent the outlier low point HCT looks unaffected. . At Dx PLT was much more out of range than was HCT so I was quite surprised to see PLT not going way higher here.
No doubt these would rise at at some point. But this persistence is not known for either HU or Rux. Maybe with good allele reductions on Rux it could be similar, no data I know of.
CMPs remained all in range, but I had no trouble there while on IFN.
I won't know longer results since I'm on Rux now, in hope immune troubles will improve.
The IFN experts long discussed IFN holidays, but usually after ~2years of therapy. This is an example of some persistence after just 11 months. This is one reason I hope to get back on IFN. I guess that one needs good CHR response to benefit from this persistence.
It's interesting that my counts were way down at the time of my reaction as seen here. I suspect the vax reaction (see my posts on that) messed with both IFN-a and IFN-gamma. Gamma can be a bad actor in immune troubles and vaxes can get both worked up from what I've seen. I may have had too much of a good thing here and killed the party. I wish there were standard IFN blood tests.
More broadly the lesson for my situation is to dose IFN the min required for CHR rather than go for alleged max allele effect. The Besremi study found no relation of allele to dose while there was allele to CHR as I've posted. I needed ~75 for CHR, while I was on 140. Result was regular malaise and maybe the mess I got into. Dr agrees if I resume it will be <100.
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This maybe a dumb question but I honestly don’t know. Would Besremi be considered “high” dose INF alpha as it is concentrated and long acting or low dose? I am getting prepared for my neurology visit tomorrow. I am still not sure he would want me to take anything else til I see him tomorrow. And what he would add! Maybe beta? Will find out. I am hoping we can just see if Besremi may work for both. But didn’t know if you knew especially since you had problems.
Besremi is neither high nor low dose. Same with PEG. The dose is easily selected by how many mcg are injected. But Bes is designed to be longer acting than PEG with more even drug levels in the body. In that way it may hold a lower peak dose and the mfr claims it is milder in its effect. But some members tolerate PEG better, so it's not all that simple.
In contrast the early IFNs had extreme peak drug levels since they were not "pegylated" to control the release rate.
My current concern is any IFN may aggravate my neuro problems. There are some rare case studies with IFN causing peripheral neuro issues, I'm qualified to be one I think, with the vax reaction adding confusion. But MS can benefit as we are discussing so look fwd to your improvements.
I would not expect any Dr to Rx both alpha and beta together.
I'm hoping to get to more normal conditions before trying to resume Bes.
At this point I’m not sure of anything but I had been under the impression that allele burden needs to be at or close to zero to be rid of this disease. My recent experience suggests there are more forces in action other than the mutant CALR. I’m waiting to fully understand my new BMB to know about other mutations in my case.
But speaking of durability I was hoping for lasting remission from peg but also ended up with a neurologic issue. . My allele burden never got below 30% after 3 years on peg but then rose up to 50% as my platelets dropped to 350k when I started having weakness in my feet in July 2020. I’ve heard CALR people have burden and platelets go in opposite directions. Then in 2021 when I finally stopped peg my platelets never went over 900k only half of the original 1.8m when I was diagnosed and feeling fine almost 9 years ago. But I felt extremely sick and neuropathy issues didn’t improve. One well known neuro thought my problem had nothing to do with peg so I took one more dose in February 2021 and it tore through me like a persistent lightning bolt. LOL. I can laugh now but it was just awful. I’d love to be able to take peg again but all my docs now agree it’s probably not a good idea. I felt best while on it.
How did you conclude a vaccine caused your neuro issues?
The experts use a term MRD, min residual disease, for the lowest alleles. This is usually below 2% but some use limit of detection which is ~0.1% or less these days. At this level long term cessation of IFN is considered. But Dr Silver also looks at marrow histology, this can be a tougher goal.
My test here was not planned, see my post "Cope with Hope". But it is neat to see what can happen with allele at 8%.
It will be good to know about any other mutations you have, and which type CALR.
I had Dx of brachial neuritis (Parsonage Turner) after the vax. This is a known possible vax, and viral infection, effect, and it came out of nowhere. I also had various strange effects right after and longer after, the flu vax. To make the connection official there is a status at 6 months after to recheck neuro issues.
It think it was a combo of IFN, Covid vax, and Flu vax all interacting. But the Covid vax the week prior felt normal, flu vax started it all. But a firm conclusion likely is never possible. There are a few case studies of IFN and neuro, but my neurologist also said my symptoms do not look like an IFN source.
Agree on that "one more dose". Tore me apart too as I posted, so no question it was a source of something. Absent that I might have got thru with just the resolving neuro issues.
I opted to start Rux esp to address the neuro and autoimmune troubles. Jak-i's are only recently being recognized as valid therapy for these conditions. Most pts get different Jak-i's that don't lower blood counts. So far it seems Rux could be working for me. If I get back to normal I might resume lower doses of IFN, but I think IFN is risky while autoimmune /neuro issues are cooking.
I suggest you discuss Rux with Dr if it's an option for your ET. We have a convenient option to use it on-label for MPN (maybe ET?) while off label for autoimmune/neuro troubles.
If you do resume IFN, titrating very slowly is wise I think, I will start extra low and slow if I do restart.
Thanks very much for the great info. I don’t have many negative tests other than my platets are elevated (722 currently) and my WBC and RBC are low normal. Protein in my CSF is twice the upper limit but no doc seems to be alarmed by it.
I was exposed to Covid a few months before my neuropathy symptoms in my feet while on peg with my plates in normal range. At the time I also picked up a weird extra burning in my lower back, I also had a mild TIA a month before the weekness started. A couple docs have suggested I have long Covid and one suggested I have an autoimmune problem causing my neuropathy. So I don’t know what the heck is causing so much sick flu like headache and weakness but I have read Rux and other jak inhibitors can be used for long Covid and reducing inflammation (hopefully in my lower back)
One other weird thing is my sick flu like head gets noticeably worse if I take vitamins especially D or B12.
I started in Rux 3 weeks ago and sometimes I feel like I can walk better but nothing really obvious.
Yes agree if/when I restart INF is will be very low and slow. Would love to feel good again.
Have you done the neuro electrical tests EMG, NCS? I expect some of your motor results were abnormal. These tests are a good way to track any improvements.
Neuro can take a very long time to resolve, years sometimes. But it may not fully resolve. I'm making progress by some criteria but the nausea in my arms and hands is a problem.
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I'm 1 week in on Rux.
Here is a sample of Rux in the literature:
"Finally, the potent anti-inflammatory and immunosuppressive properties of ruxolitinib can be exploited for the management of severe conditions including autoimmune or inflammatory diseases"
Neuro and autoimmune seem to have a lot of overlap, this was my motivation to request Rux.
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Another agent that correlated to improvement for me was restarting Curcumin. A couple weeks before starting Rux I noticed improvement. Of course correlation is easier to prove than causation. I'm still taking Curc while on Rux. But none of these might have helped at all in my worst days.
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Reducing Besremi dosing 
