CALR type 2 here with severe neuropathy that came on after 4 years of peg. Could be a coincidence or from the peg, not sure. I also have an antibody that is known to attack nerves called myelin associated glycoprotein. Traditionally it is known to only effect nerves if you have an mspike/myeloma but repeated tests do not show me having that. IMO my ET might be interacting with the MAG AB in a non traditional way but no doctor seems to agree. IMO the docs may just have not connected the dots to a CALR ET situation yet.
7 weeks ago I was given 3 days of IVIG in an attempt to improve a motor neuropathy in my feet. It’s not scientific but the weakness seems to have gotten a little worse and I have felt much worse with a continued sick dizzy feeling in my head to go along with it. Most notably about a month after the infusions my white cells dropped to 1.0, neutrophils to .67 and lymphocytes to .17 and platelets to 262k. I was taking my usual 1000mg Hydrea at the time the infusion started but stopped it completely two weeks after as counts began to drop. The low point was one week after stopping all Hydrea. He was so worried my hematologist did a BMB on me that was basically unchanged from one I had a year ago. The counts have come back up to my previous baseline and I’m back on Hydrea.
I’m being advised by my neurologist to do more IVIG to try and improve the neuropathy but the side effects that include such a dramatic drop in blood counts are very concerning.
It also seems quite interesting that my cells especially platelets could drop so dramatically from IVIG. Prior to the IVIG they were just under 600k on 1000mg of Hydrea daily. The white cells and lymphocytes were just a little below normal. Neutrophils well into normal range. IVIG can cause counts to drop but not as much as mine did.
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George1976
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Sorry to hear about the challenges of managing the ET along with peripheral neuropathy. It sounds like it is hard to determine exactly what is causing the PN. It is a rare adverse effect from Pegasys. Given that Pegasys can cause autoimmune disorders and that anti-myelin-associated glycoprotein (MAG) neuropathy is a rare autoimmune disease, it seems reasonable to think that the Pegasys could be involved. Given that your doc switched you off the PEG, it sounds like that is is a working theory.
It is worth noting that PN is also a potential adverse effect of hydroxyurea. It is hard to tell what to do but I would wonder about Jakafi, which would be off-label for ET. That is something to discuss with a MPN Specialist.
It sounds like you are experiencing significant cytopenias with the IVIG. I am wondering if it would be appropriate to suspend the HU prior to doing another round of IVIG. Perhaps a different treatment approach to the PN would be a better option. This is something to review with your care team.
In a complex case like what you are experiencing, a very high degree of collaboration is needed between the providers. If I were in this situation, I would seek a second opinion from an institution with both a MPN treatment center (MPN Specialist) and a neurology department with a specialist who is familiar with your form of peripheral neuropathy. Involvement of an immunologist might also be indicated. Your best recommendation would come from an integrated team approach. This would likely be a large teaching/research hospital system. Depending on where you live, this could involve significant travel but it would be worth it.
Please do let us know what you learn and how you get on.
Thanks Hunter. I’ve been traveling around the country quite a bit already to several well known research hospitals/universities and despite my best efforts I’ve not been able to get any of these neurologists and hematologists to put there heads together for me. I’m personally conveying the info between them and it’s not real effective.
I tried Rux last year and had a strange euphoric reaction to it at first. Then it almost felt like a stimulant that I was addicted to, giving withdrawal symptoms if I missed one dose. Plus my platelets kept going up so I went back to HU after 2 months.
Yes, if I do another round of IVIG I’ll definitely stop HU at least a week before. I do agree something in my immune system is likely way off but the immune docs I’ve seen only treat hay fever and reactions to bee stings. I hear you need to take at least two infusions of IG to see any benefit so I may try and tough it out and hope for the best.
We may share the permanent autoimmune outcome from that Last Dose of IFN that is in the Black Box warning. I see your prior post:
" In February 2021 my last dose of Pegasys gave me horrible neuropathic pain in my legs."
and "All the while I am feeling absolutely horrible almost all day and night every day" I relate all too well. Have you been checked for POTS (Postural Orthostatic Tachycardia Syndrome)?
"one neurologist thought I had an autoimmune disease driving my neuropathy" What have you learned since this old post?
You likely have seen my post with Last Dose in the title. We had the warnings but they were not obvious enough to act on and our Drs have no idea. I wish my neurologist had known.
Has your Dr discussed SCIG? This is sub-cutaneous, sort of like a PEG injection but slower. It's supposed to have milder effects than IV, but it's relatively new and not all Drs, or conditions, may be suited.
Could you rechallenge (try again) with Rux, but titrate up very slow while slowly reducing the HU? Some are taking the combo longer term. Rux, like IFN for some, can take a while to take effect. My PLT is higher on Rux than it was on IFN or HU.
Rux is known for adverse reactions upon quitting but your reaction seems more than usual.
Thanks EP. I do remember your autoimmune story related to IFN. You’ve got Sjögrens? Haven’t seen a post from you in a while, Hope you’re getting along as well as possible.
I think i was tested for POTS and I think it was negative. Pretty sure my heart rate does not increase when I stand up. The sick feeling in my head often literally starts in the morning as soon as I wake up even before I open my eyes. I’ve thought it could be platelets but i feel it even when they are lower. It could be that I am just sensitive to some byproduct of the ET or I have neuropathy in the nerves on the surface of tissues in my head.
I was checked out extensively for autoimmune diseases by a couple rheumatologists including Cleveland Clinic and nothing was found except mildly elevated tnfa.
I have had low gamma globulins and back in March they were below normal but the other IG’s are normal.
My neurologist probably would not endorce SCIG as he wants me to take 55 grams a day for 3 days once every 4 weeks for 3 months. I don’t think SCIG would deliver the large dose he is recommending.
My experience with Rux was pretty bad too so I’m not sure I’d want to try it again. But I might at some point. Never say never.
If the IVIG doesn’t pan out I’m going to push harder for a neurologist and hematologist to work together at a research hospital. A few hoops to jump through to make it happen but I have a possible path to that.
My last hope is that this is all (or mostly) linked to the ET and if one of these new CALR meds work out maybe it will fix me or at least fix this sick feeling. I find it very interesting that IVIG lowered my platelets so much. Makes me think there’s a possible link from ET to the immune system. I mean my platelets will run up to 1.8 million with no meds. And to think they came down into the 200k’s on IVIG a week after stopping all Hydrea seems almost like a miracle.
Correct I "caught" Sjo via vax and IFN. It is an evil opponent that is among the more common of the very rare IFN Black Box events.
I am still posting but not so often. You're the only other member I know that had an extreme before and after Last Dose experiemce. There are several who got Sjogrens while on IFN, some quit in time others did not.
It is possible to have auto-immune (A-I) while near all A-I tests come back normal. I learned this from the Sjo forum, where I asked about it specifically, and other sources. It leads to huge frustration for some pts trying to get the Dx.
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I looked into IG dosing a bit. It seems SC is more accepted in Euro while less commonly used in the US. In this report the issue is discussed:
"Those ...who are on high-dose therapy should be aware that a number of European studies have documented that SCIG seems to be effective."
Interesting there is a modification (hyaluronidase) to the active substance that allows for longer dosing and more even levels in the body. (brand HYQVIA ) This is similar to Pegylation in IFN. The report implies this further helps tolerance of higher SC doses. A promising new SC therapy (Yyvgart) for Sjo also uses this hyaluronidase. (phase 2 just finished)
This deep report describes specific agents in use:
"Currently, there are four FDA-approved products that can achieve high-volume s.c. delivery of mAbs; these are formulated as fixed-dose combinations with recombinant human hyaluronidase "
It doesn't mean SC is appropriate for you at all, but worth asking about in case it might lower your misery in some way.
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Understand on the Rux, you had a fast really bad outcome. With your unusual issues below it could be connected to that.
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Interesting on the reduced PLT with IVIG. It seems usually associated with increase levels and helping with thrombocytopenia can be a reason to use IVIG . This report has some case studies with your unusual contra result:
"This is the first reported case of thrombocytopenia as a possible adverse effect of IVIG."
Has your Neuro discussed reasons for the unusual result? For ET it's not necessarily an "adverse" event but does call for more inquisition. I agree you need a Hem in this mix.
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I see you have misery in the head and pain in the legs. That is a whole system effect. Sjo doesn't leave any system alone so I relate to such troubles.
Thanks for the thoughts EP. A lot to think about. The neuro leading this just says he’s seen counts drop but not as severely as mine did. My local hematologist doesn’t know what happened. One of the MPN experts I communicated with suggested the IVIG may have caused my spleen to take up more cells than usual.
One additional snag is that things that work on JAK2 don’t always work as well on CALR. Which is why there is great hope for the new CALR drugs.
My mother was suspected of having Sjögren so it could be that I simply inherited the neuropathy from her and the ET and/or meds are not playing much of a role.
Welcome to the club of rare reactions. The spleen theory would seem to go with a temporary enlargement of it considering how dramatic the effect is. Maybe an ultrasound or other check after the IG would be telling.
You're right a family history of autoimmune adds to the odds of having one. Sjo has loads of neuropathies. I recently saw a Sjo specialist who was intrigued by my Sjo that came "out of the blue".
Agree on Jak2 vs Calr. The cell therapies are quite hopeful. Same with some autoimmunes, there are early signs of curative solutions in trials now.
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Pegasys and low White cells 
High White Blood Cells
Took some time but my platelets finally dropped on Peg
Veins Tapped, Blood Trapped, White Cells Zapped ! 😎
Unbearable itching! Any ideas to calm it down?
