A recent post discussed the trial in China on the high dose protocol for Besremi. The discussion focused mostly on VAF (mutation) results. The other important item we can miss is CHR (blood response)
I made a plot comparing CHR vs Time from the Proud/Conti PV trial to the recent high dose trial. The ContiPV has a text table I used for this plot. Both trials used high maintenance doses, Conti PV being ~400mcg, but the Chinese trial started more aggressively.
Most trials of all 3 of our drug types report some loss of best CHR over time, these follow this trend. Assuming they are comparable, this plot suggests a possible faster best-CHR burn out with the high dose protocol. Maybe the Chinese trial will report a third year to get a better comparison.
One subtle item in the Chinese trial is the starting the premise that CHR and MR (molecular) have been assumed to be connected while this trial showed a disconnect. Some confirmation that this CHR-MR connection has been previously acknowledged, I've posted often on it. If the high dose method breaks the connection, is that desirable? Or is it instead just bringing all the effects forward?
A related question, if best-CHR burnout is faster, will VAF rise start sooner. Or will the rise be avoided/delayed? The median starts slightly rising after 5 years in the IFN trials where this was knowable.
Very good observation. I can only one point to supplement. Dr. Gisslinger said in his presentation last October that - If I understand it correctly - there are benefits come only with long term use of interferon. Molecular response does not provide sufficient explanation and he also mentioned in the analysis of earlier trial there did not seem to be a correlation between dosage and time to achieve HR. My understanding is that he refers to the benefit for individual patients with different dosage. There seem to be difficult to say doses higher than response dose yield clinical benefits. I could be wrong though.
Both Rux and IFN share that long time for best benefit. IFN uniquely has wide variations in effective or required dose for CHR as Dr said. I would have been good (and likely wreckage free) on 50 while some require 500.
Separately from a vague assemblage of all the reports I've seen I'm increasingly thinking that MR benefit is tied to non-driver mutations. The presence of certain ones might create resistance to being disease free even with complete Jak2 response. The existence of triple neg ET is one cause to support this idea. We may get an answer if the new Jak2 drugs that target Jak2v619f so well continue thru trials. There will be multiple pts free of Jak2 allele who should be disease fee if Jak2 is the only disease cause. All this still leaves unknowns for CALR or MPL.
After 4 years of Peg my CALR HR was great, platelets in mid 300k range while VAF was going up. Then came severe neuropathy which lasts until today. VAF for me dropped from 49% to 39% after a trail of IVIG last year which also beat me up pretty good for about a month with night sweats and severe cytopenia. Now i suspect the entire ET thing could be an immune system disorder.
The type of neuropathy and experience you've been thru suggests autoimmune (A-I) reaction for which IFN is known, and unfortunately you may be among those, including me, for whom it's permanent as in the IFN label. Did you get the A-I panel tests?
Did you get any further conclusion for the anti mag A-I condition? If you've been unable to get a clear conclusion on any of the neurological Dx's one condition to explore remains Sjogren's for which IFN is associated among the rare A-I reactions. This disease is very under dx'd esp among men who present with stronger disease on average. ET does involve the immune system as does almost every medical condition. But MPN's are less known for the extreme permanent sort of neuropathy you are suffering. This report has some good info on neuro and Sjo, esp focused on seronegative if your SS-a result was negative.
No diagnosis yet but a few tests seem to be leaning towards Lupus. Anti mag still going up. Also when I take even 1000iu vitamin d my flu like feeling is a lot worse for a day. Vitamin D is below normal too.
And haven’t been able to get a doc to order the tests you recommended but am still hoping one will soon.
Was thinking about trying subcutaneous IG since the IV version hit me so hard but then I think I maybe should instead do things that won’t rev up my immune system too much since it seems to be my enemy.
I also have a strange one, EPO well over limit. Seems your Drs can't tell you what's up with your D same as my EPO.
SG IG is supposed to be easier tolerated, and be longer lasting in the body. I think these days IVIG is best reserved for when needing more urgent effect.
If your Dx ends up Lupus, that is as serious as its close B-cell mediated sibling Sjogren's, so not too fun. And it shares a tendency to stronger presentation in men, for whom both are ~10% of cases. Both are known as IFN rare events, But a "good" thing is Lupus is much better understood and respected in the med field and has treatments unlike Sjo. Most hopeful if it's Lupus is the large number of Cell trials popping up for the indication. (Near or Every A-I cell trial has Lupus included) One has breakthru status with case studies indicating curative effects. And MPN pts have a good shot to qualify for these trials. I can give you more info, but maybe wait till you know more definite on that Dx. Even if it's really Sjo, or a combo of both as is known, getting the Dx as Lupus puts you in a better place with these new Tx , so maybe ok not to push on too many more tests.
I have been let down by two cell trials near me for Lupus that considered and then passed on Sjo. The Tx is the same. These cell trials are distant relatives to the exciting therapies for CALR ET.
Looking back to our posts, I think we may share the experience of a "Last Dose" of IFN, where we felt somewhat not right, suspected the IFN, then one last dose clearly triggered a quick, large and durable adverse event. For me I can know this in hindsight. You mentioned "My last dose of Peg caused fairly intense burning in my upper abdomen and lower legs." Is your experience similar to mine in this dose being a life defining event , or would you say something different?
We may also share a triggering event while on IFN, you noted the early 2020 Covid, mine was likely the botched vaccine. A-I's are prone to triggers, including viral or bacterial infections. I also had the early 2020 Covid, but no long C and well before IFN. Covid infection is known to increase this risk:
"...lupus (SLE), rheumatoid arthritis, or Sjögren’s syndrome, have been noted in some patients with Long COVID"
Another risk factor for many autoimmunes is a history of a severe case of mononucleosis. I had that as did near 100% of those answering in the Sjo forum. The Epstein–Barr virus is being implicated with new research.
Yes, my last dose of peg I believe caused a lot of pain in my legs and abdomen. I’m usually a little dramatic so I was restrained when I said fairly intense. I took it about 10 hours before it hit me and I’ve not experienced anything like it since that day, luckily.
Looking back now after speaking to so many docs and conversations on this forum and searching the internet including ChatGPT, I think I must’ve picked up an AI disorder in early 2020 in combination with peg and likely exposure to COVID that resulted in chronic tendency for some microvascular clotting, not enough to show up on a vascular ultra sound of the large veins in my legs for example. This seems to be related to antiphospholipid syndrome or less likely a mild form of hemolytic anemia, based on me testing very high for ACA IGM. The ACA IGG would be worse (I’m negative for that) but since I already had ET the two together I believe are causing me microvascular trouble. I’m pretty sure the AI itself or the microvascular dysfunction in body parts where there was already inflammation like my lumbar spine attracted an extra share of microvascular dysfunction which has led to or enhanced the progressing neuropathy in my lower legs. Of course I could be wrong on part or all of this but since taking more aspirin (a whole 325) daily it seems to help me feel noticeably better and walk a little better.
During that last 9 months of peg use the AI was likely establishing itself and gradually peg was aggravating it more and more until the last dose.
Now almost 4 years later my gastrointestinal issues are basically gone after working hard on my diet. My sick flu like feeling is better but occasionally still bad. Otherwise all that’s left is the neuropathy which shows some signs of improvement now and then but I’m not expecting much there but will always hope and work for more.
There’s a remote chance I picked up some kind of AI from Lyme which I had and was treated “successfully” for 20 years ago which may have contributed to development of the ET which in my case showed signs of starting, 12 years ago. This is a theory that’s nagged me for a while but cannot prove beyond still testing positive for IGM P23. Here again you need another Lyme marker to be positive to officially say you have Lyme. My sick head feeling that’s been bothering me for 4 years is a lot like how I felt when I had Lyme officially 20 years ago.
Can’t stress enough to get on a great healthy diet and exercise as much as possible. A healthy gut is foundational to good health. I remember when first started treating my ET 10 years ago the anagrelide almost immediately gave me gastrointestinal issues and tingling in my feet. Stopped that after two years and went on peg. 4 years of that I think was not allowing my gut issues to heal perhaps and all came to a head on that last injection.
With those gut troubles, a good diet is esp indicated. But it helps with just about everything else too.
Autoimmune seems to have biases in so many other conditions. Lyme is one for sure. Mono is a biggie. Could be any episode where the immune system is given a new or hard task can be a precursor to A-I. I agree your early covid (what scientists call the Wuhan HU-1 strain) could be a big part of it.
So we do share the experience of a specific last dose of IFN leading to identifiable long term jump in events. I'm not aware of any other members with this experience from one dose. It seems most of yours are improving except the neuropathy. Great that you were able to do something to help yourself get better. Maybe ever more time might help the neuropathy some.
Interesting that mine started with formal neuropathy Dx from the botched vax, and that has actually healed over a year or so. But the 2nd act that blew up with that last dose is not going anywhere.
I did find exercise was a cure to fatigue while on IFN, I would get up and move around vigorously when feeling droopy. But that no longer works with the Sjo.
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