ME and PEM recovery via Cyclophosphamide (personal story)

horton6 said:
@siobhanfirestone With any recovery stories, it's useful for me when they include details of how long they were sick, how severe they became (examples of things they could or couldn't do on a "normal" day), what symptoms they experienced when they overdid things at those levels, how they titrated the dose of whatever they took, how long it took before they noticed improvement, why they think it has plateaued if they are somewhat recovered but not completely, and what they mean by common acronyms or comorbidities (it seems lots of people have a different experience of what POTS or MCAS meant for them, for instance. Some people still call it POTS when it's not provoked by orthostatic challenge, and just refer to any tachycardia as POTS).
Click to expand...
roger, will try an be as descriptive as possible.
 
ok everyone, full remission story.
tldr: I started with severe ME/CFS as Long COVID and POTS and SFN in 2022, extreme PEM that hits 24 hours after an activity and disabling brain fog. Initially CBD felt like it reduce inflammation a little so i could walk maybe 4000 steps without PEM. Worked through this part time but it took everything I had and even counting numbers sometimes was hard. Read some science, was going to kill myself from poor QoL. Did chemo, reduced IgG specifically based on autoimmune theory, and focusing on plasma cell drugs nothing else as rituximab failed. I am in remission, no limit on steps or activity. Two random issues from POTS remains, i have a hightened feeling of anxiety thta is driven by body not thoughts sometimes, and i get very sweaty sometimes, mestinon has helped a lot (interestingly tried this drug before chemo and it did nothing). I am out living life now and very happy, planning tavels around africa next year.

So not sure how to say this but im in full remission from me/cfs. Dont have PEM, have not had extreme fatigue or tiredness for ages, brain fog is gone completely, I can exercise fully without PEM but running at the moment seems to increase my anxiety from POTS which is not nice. I also might have PTSD from medical trauma, not sure. Seeking a therapist.

I did this protocol; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201056/. I read a LOT of good science and came to the conclusion, after reading how poor Rituximab is for most conditions, that ME/CFS is either a b cell driven disease or a novel autoimmune disease. I then based my treatment on reducing IgG. I tried darataumab from india, this is legal in my country and I have IV training, but didnt lower IgG and had no corresponding effect at all. I then did the chemo, and from maybe infusion 4 ish (which corresponded ewith my IgG totals reducing to 4, it started at 8), I felt a huge change in my body, and my POTS went very strange. From then on I felt like my ME/CFS symptoms were vfery very slowly sort of going, this was about month fourish. I am honestly still actually getting better. I had monitoring from a doctor, one instance of anameia and I had an iron infusion for that.

A part of that might be that chemo also damaged my nerves and caused a lot of sickness, like actual vomiting. Thanfkfully these issues are slowly fading.

Im here to answer questions, and for the future I will come back and report if I have a relapse, consider me fine if I dont report. I consider myself in remission not cured, but I now know what it is for me and im so so so happy and grateful to the doctors who are researching this. Hopefully in the future there is a drug that is not chemo that is focused on plasma cells that i can get access to. Until then, im out enjoying clmbing and flirting with women again. I am consdering a IVIG infusion to make sure im not immunocompromised much whilst COVID is around.
 
Thanks for writing about your ME/CFS and recovery @siobhanfirestone. Sorry the mods didn't see your question about where to put the thread. The treatments section is fine, we will just expand your title to include the full name of the drug.

(If ever anyone wants to ask about where to post a thread you can start a conversation with a mod, or just post somewhere and click on the 'contact moderators' button to ask us to check the location.)

I think the idea of a problem with long lived plasma cells is plausible. What makes you sure that it was the treatment and not just time that made you recover? People do naturally recover from post-infection syndromes in that 2 to 3 years after onset range.
 
Hutan said:
Thanks for writing about your ME/CFS and recovery @siobhanfirestone. Sorry the mods didn't see your question about where to put the thread. The treatments section is fine, we will just expand your title to include the full name of the drug.

(If ever anyone wants to ask about where to post a thread you can start a conversation with a mod, or just post somewhere and click on the 'contact moderators' button to ask us to check the location.)

I think the idea of a problem with long lived plasma cells is plausible. What makes you sure that it was the treatment and not just time that made you recover? People do naturally recover from post-infection syndromes in that 2 to 3 years after onset range.
Click to expand...
There was not a chance I was getting better without medical intervention, i am actually finding it difficult to go back and reflect on how ill I was as it’s so traumatising. I was actually starting to decrease before I started cyclo.
I had also tried a bunch of things to no avail; aside from rapamycin than helped brain fog and put me into all the autoimmune literature.
The extreme response and like “snap” at the exact point (with blood tests) that my IgG started to get really low is evidence enough for me, as I said it was about month four.
Tested a lot of other stuff like T cells and NK cells and nothing else correlated.
Combining with the evidence from Scheben etc I think it’s a solid case study for autoimmune/ b cell component. People should look more into the literature on rituximab, it’s nowhere near as powerful a drug as I think some believe and has failed in several key trials for autoimmune diseases like Sjorgens. I know lots of people on it whos IgG didn’t drop.
 
siobhanfirestone said:
I know lots of people on it whos IgG didn’t drop.
Click to expand...

Just to be clear, when we introduced rituximab for autoimmune disease it was never intended that it should lower IgG levels. The aim was to abort self-perpetuation of auto reactive clones without significant lowering of IgG. Repeated use of rituximab does produce a low IgG in some but there have, unsurprisingly, been infection deaths in this group. Maintaining low IgG levels has the expected severe risk, even if most people survive pretty well.
 
Jonathan Edwards said:
Just to be clear, when we introduced rituximab for autoimmune disease it was never intended that it should lower IgG levels. The aim was to abort self-perpetuation of auto reactive clones without significant lowering of IgG. Repeated use of rituximab does produce a low IgG in some but there have, unsurprisingly, been infection deaths in this group. Maintaining low IgG levels has the expected severe risk, even if most people survive pretty well.
Click to expand...
Yeah your right, I’m not discrediting the game changer that RTX was for certain autoimmune diseases either- but it’s clearly not the one for a disease that at least in my case matched significant improvement with a vast lowering of IgG (didn’t even know it was the case till I got my bloods about two weeks after the signifiant “snap”)
I’m doing IVIG soon for the very reason you give - Covid could kill
 
Siobhan has kept me updated on her treatment journey. This is my summary which I wrote for another group and she has checked and approved. I hope a few additional details help.

She was of moderate severity with typically 4000 steps per day. Brainfog and PEM were the symptoms that caused her the most frustration. She was (with difficulty) able to work part time remotely. She has tried many treatments since getting ill and had absolutely no response to most of them which makes it less likely she is now experiencing a (very dramatic) placebo effect.

Before cyclophosphamide the drugs she best responded to were steroids and rapamycin in particular with regards to reduction in brainfog and prevention of PEM. ME patients who respond to rapamycin are rare.

In December 2023 she did two doses of daratumumab. It gave her the expected side effects, but failed to reduce her Igg. She could not afford more daratumumab so switched to bortezomib between January and February. Bortezomib caused serious constipation and grade two neuropathy.

Although she did not notice any symptom improvement before starting cyclophosphamide then it is possible that daratumumab and bortezomib did contribute to her subsequent improvement through cumulative immunosuppression. However cyclophosphamide is likely responsible for most of the improvement that she is now experiencing.

She did five doses of IV cyclophosphamide dosed at 800mg/m2 spaced three weeks apart. The first dose was in March. This is higher and more frequent than the Norwegian protocol which starts at 600mg/m2 followed by five monthly doses of 700mg/m2. Since she did five doses not six so the cumulative dose is the same.

She felt VERY ill for several days after each dose and found the whole treatment period emotionally very difficult.

She experienced hair thinning and mild bladder irritation. She is still experiencing neurological foot pain, but is confident that this will pass.

She noticed a definite improvement in her symptoms after the second dose and has steadily continued to improve since then. She introduced rituximab after the third dose, but since she was already strongly responding to cyclophosphamide it is impossible to know what if any role that is playing in her continued improvement.

Six months after her first dose she has improved from moderate to near full remission. She no longer takes rapamycin for brainfog as she says that is now 90% better.

Compared to most of the study participants I would say she is a very strong responder. This could partly be due to the increased dose and higher frequency of dosing. Based on the study data it is likely she will continue to improve over the coming months although no-one can predict what will happen in the long term.

I also did four monthly doses of cyclophosphamide per the Norwegian protocol. Since I did not experience a response I did not continue and ten months after my first dose my symptoms still have not changed. Our sample of two supports the Norwegian data of an approximately 50% response rate.

Siobhan’s (pre daratumumab) baseline Igg was 8g/L. I did not measure before treatment, but three months after the end of treatment mine was 10.8g/L. This also supports the Norwegian’s (tentative) observation that responders have slightly lower baseline Igg than non responders.

I have no lasting problems from cyclophosphamide and I do not regret doing it. The unpleasant experience was absolutely worth it for a chance of long term improvement and to know I gave it my best shot.
 
Last edited:
Please everyone be aware, however good it is to hear stories of improvement, that from a scientific point of view we are talking of improvements or recoveries, but not responses to treatment. Without controlled data there is no way of knowing which if any of the drugs contributed to improvement in a naturally remitting condition. The person improving may subjectively feel confident that drugs helped but nobody else is in a position to judge.
 
Jonathan Edwards said:
Please everyone be aware, however good it is to hear stories of improvement, that from a scientific point of view we are talking of improvements or recoveries, but not responses to treatment. Without controlled data there is no way of knowing which if any of the drugs contributed to improvement in a naturally remitting condition. The person improving may subjectively feel confident that drugs helped but nobody else is in a position to judge.
Click to expand...
about 5% of patients getter better with no intervention.
 
siobhanfirestone said:
about 5% of patients getter better with no intervention.
Click to expand...

Maybe, in a different context, although it may be more like 20% long term and higher in young people and loads of members here report having had remissions even if not permanent.

More significantly, the getting better rate on both placebo and rituximab were substantial and the lack of difference suggests that rituximab was doing nothing more than being a placebo.

People in trials or trying drugs off label have a much higher improvement rate than the general statistic - for reasons that may be very complicated.
 
Jonathan Edwards said:
Maybe, in a different context, although it may be more like 20% long term and higher in young people and loads of members here report having had remissions even if not permanent.

More significantly, the getting better rate on both placebo and rituximab were substantial and the lack of difference suggests that rituximab was doing nothing more than being a placebo.

People in trials or trying drugs off label have a much higher improvement rate than the general statistic - for reasons that may be very complicated.
Click to expand...

A placebo response is much less plausible in a patient who has tried and completely failed multiple strong (and in some cases expensive) treatments like daratumumab, bortezomib and several others.

A coincidence is also less plausible when after over two years of stable or worsening disease you see a dramatic improvement weeks after starting treatment.
 
Last edited:
dankeen said:
A placebo response is much less plausible in a patient who has tried and completely failed multiple strong (and in some cases expensive) treatments like daratumumab, bortezomib and several others.

A coincidence is also less plausible when after over two years of stable or worsening disease you see a dramatic improvement weeks after starting treatment.
Click to expand...

On what do you base that opinion? Do you have some particular experience with running trials?

Having been studying the research in ME/CFS for ten years I don't think we can make statements like that. There are many stories of people with ME/CFS suddenly getting better after long periods unwell. They include treatments like the Lightning Process. Unpredictability of time course is perhaps the most characteristic feature of ME/CFS!

'Placebo response' in the loose sense relevant here, includes a whole of confounding factors that mean that people often improve in the context of treatments for reasons not directly related to a pharmacological action.
 
Jonathan Edwards said:
On what do you base that opinion? Do you have some particular experience with running trials?

Having been studying the research in ME/CFS for ten years I don't think we can make statements like that. There are many stories of people with ME/CFS suddenly getting better after long periods unwell. They include treatments like the Lightning Process. Unpredictability of time course is perhaps the most characteristic feature of ME/CFS!

'Placebo response' in the loose sense relevant here, includes a whole of confounding factors that mean that people often improve in the context of treatments for reasons not directly related to a pharmacological action.
Click to expand...
I had a feeling that any data presented would be met with a luke warm recentption here, even though there is enough data to present as a case study. I was not in a trial.
I feel that this attitude is massievly letting down patients who are at a risk of suicide about 8 times higher than the usual public. Everyone here can make thier own mind up with my findings, if you wish to ignore the woods for the trees I cant do much to change that, althugh i do understand why there is rigeou in the medical system to ensure your not giving patients nothing, or worse sometihng that hurts them.
I wish everyone the best and to hopefully be a part of these magic people who achieve remission without medical intervention. I will likely be back in a few years either due to LLPC or if an infection triggers it again, and will work to lower IgG then in order to do this again.
 
Jonathan Edwards said:
Without controlled data there is no way of knowing which if any of the drugs contributed to improvement in a naturally remitting condition.
Click to expand...

This is exactly the problem. I’m not aware of more than 5 (max 10) ME CFS official drug trials (with controlled data) going on at the moment, and most are very cautious - trialing drugs that are low risk (e.g. LDA, LDN, etc).

And, we actually are talking here about an illness that is NOT a naturally remitting condition for most ME CFS patients. For a a huge group it’s slowly Progressive. And the worst 25% is (very) severe. With a decent chunk of that bedbound (5% ?). We know it can lead to death.


So I do think we need a Paradigm Change by the Medical Communit to allow more experimental treatments.
– Just as with a very serious condition like M.S. where there’s a long list of treatments (e.g. also Cyclophosphamide treatment)
- IMO Doctors should either facilitate - or be willing to give minimal care and guidance - when well-informed patients are willing to experiment

As The reality is: we will have more and more patients trialing themselves
-because ME CFS Research is still going at snail space (ME Budget = 6% of M.S. Budget - acc. to CDC data 2020)
- Realistically It will take a decade (or more) before we have an accessible breakthrough treatment
- The numbers of patients have more than doubled / tripled with Long Covid
- And Publications and scientific/medical information is becoming more and more accessible to patients

Trialling comes with (sometimes high) Risks, but for many this illness can be brutal, so it can be worth it.

I hope our doctors Will soon accept this reality and take their responsibility.
To have an open discussion with knowledgeable patients, discuss drug trial publications and experimental treatments.

Often ME CFS / LC researchers are actually learning from patient’s experiments.
(E.g. Just a few weeks ago OMF researchers presented 2 cases of Jak-Stat Inhibitor experiments curing 2 patients)


I know this opinion will be seen as controversial, but it’s already happening and The amount of trialing Patient numbers are growing (specially since Long Covid ). Mostly treatments like LDN, POTS/OI drugs and MCAS stabilizers. But often without guidance of a doctor. This can be risky.


*****

So while it’s very clear we should not condone trialing heavy dangerous drugs like cyclophosphamide, we should be inquisitive about it, and try to get as much details as possible to understand a remission (o non-response).

Like what bloodpannels have been done before and after illness?
- What are the exact details of patient’s illness timeline / process?
- Smart-watch data, like steps, RHR, HRV, sleep, oxygen, etc.
- What is the list of all the treatments / drugs done before the cyclo protocol?
- Does Patient fit an ‘auto-immune profile/cohort’ ? Meaning an ‘auto-immune blood panel’, and/or responsive to to immune treatments like IVIG, Rapamycin, etc.
- Can a possible remission be ascribed to placebo when side-effects of high dosage Cyclo are very strong and mimic MA symptoms (Brain fog, nausea, Fatigue)
(The few patients that tried cyclo I talked to directly, were fitting the classic ME profile: moderate severe, 10–15 years)


By lack of enough drug trial Publications, we need to learn as much from n=1 anecdotes.


sad, but true.
 
Last edited:
Dear @siobhanfirestone thank you for sharing your story.

Do you think there is any reason why your story should be viewed any different to a person with a similar illness duration and severity that had tried various things and suddenly reports recovery in period that followed after they had also tried a supplement, the Lightning Process, a mAb against SARS-COV-2 or even Rituximab (which we know doesn't have a different response than a placebo in the general ME/CFS population)?

Would it be possible for you to present some more information on when exactly you tried various different things with regards to your illness duration?
 
Arvijansen said:
So I do think we need a Paradigm Change by the Medical Communit to allow more experimental treatments.
Click to expand...

All I can say is that having spent my life studying disease mechanisms and doing trials I disagree. We want more physicians to do small focussed trials capable of producing meaningful results. For me that meant buying £10,000 of drug from my own pocket and making up, infusing and monitoring treatments without any nurse help. I had to judge very carefully whether or not I would get a result that meant something. I have sat on trial design boards for hours agonising over how to do that. It can be done, but what we have at present is people trying out drugs in a way that provides no basis for recommending to others.

Inducing hypogammaglobulinemia (low IgG) may indeed be a way to get ME/CFS to remit but we now live with a virus everywhere such that very low IgG is likely to be associated with something like a 5-10% mortality. Immunosuppressive drugs still regularly induce bladder and skin cancers. If these drugs are used at least it should be within trials that tell us something useful.
 
You must log in or register to reply here.
Back
Top Bottom