ME and PEM recovery via Cyclophosphamide (personal story)

[forestglip]

If these drugs are used at least it should be within trials that tell us something useful.

I wouldn't imply that @siobhanfirestone describing her story is useless. Every anecdote has some worth, even if only potentially as one of many anecdotes. If fifty more people post here in the next two weeks that they had the same experience with cyclo, outside of a controlled trial, that would certainly feel like evidence of something, at least in the proximity of an ME treatment, and it might perk up a researcher's ears and motivate them to do a controlled trial. Even though each anecdote individually might only be as conclusive as this one or less, I think they add to something which can have significant value.

The more inquisitive we are about this particular experience, the more "controlled" and potentially useful we can make it, in the broader scheme and the long run.

Absolutely not recommending people try this drug on their own, and there might be something to the argument that openly discussing such an anecdote presents unnecessary risk of others trying it and being severely hurt. Though I think the discussion being very clear and forthcoming about the risks of people getting injured might decrease the risk enough that it doesn't outweigh the value of the data.

 

[MrMagoo]

Of course this will get a lukewarm reception here, this is primarily a science forum and it is one personal anecdote. It’s nice that it helped one person but it’s not scientific. It’s interesting, it’s worthy of some debate which, is always rigorous here.

 

[duncan]

Of course this will get a lukewarm reception here, this is primarily a science forum and it is one personal anecdote.

The irony that this is indeed supposedly a science forum accessed via the internet notwithstanding.

 

[Haveyoutriedyoga]

I really appreciate the debate that has followed the story, this sort of thing helps me think more critically.

 

[MrMagoo]

The irony that this is indeed supposedly a science forum accessed via the internet notwithstanding.

I don’t understand?

 

[duncan]

I don’t understand?

Ah. Sorry. I must be dating myself. There was a time (not too long ago it seems to me) that using the Internet to uncover scientific facts or truth was considered a fool's errand, riddled with risk of misinformation, and anything but scientific.

So. Ironic?

Or not.

 

[Jonathan Edwards]

Every anecdote has some worth, even if only potentially as one of many anecdotes. If fifty more people post here in the next two weeks that they had the same experience with cyclo, outside of a controlled trial, that would certainly feel like evidence of something,

I agree that it is of interest. But there is also a risk of confusion. My understanding now is that cyclo was not what was associated with improvement here, but low IgG levels - requiring using other drugs? Cyclophosphamide on its own is not a useful way to get low IgG for any length of time without huge toxicity risks. With several drugs being used in sequence we don't really have much idea what to conclude.

I wonder if anyone with ME/CFS has had an allogeneic bone marrow (haemopoietic stem cell) transplant. Autologous stem cell treatment (your own stem cells) has been tried for diseases like lupus and MS but there is relapse. Allogeneic transplant (someone else's immune system) is much more radical in terms of immune memory - you probably end up losing all your old B cell lineage. It is a risky process but if we are looking at risky options maybe it would tell us something important. It is sort of the acid test experiment because if ME/CFS has an immune basis it would be very unlikely to start up again with a completely new immune system.

 

[MrMagoo]

Ah. Sorry. I must be dating myself. There was a time (not too long ago it seems to me) that using the Internet to uncover scientific facts or truth was considered a fool's errand, riddled with risk of misinformation, and anything but scientific.

So. Ironic?

Or not.

Ah, I think citizen science, free online education and the like has overtaken.

 

[Kitty]

Or not.

Maybe not?

The thought about the internet and scientific fact still holds, though as so many facts turn out to be wrong, it must be true of all sources.

Discussion of it is different, especially as a lot of it's about science's increasingly brazen fact deficit.

 

[duncan]

Invoking science standards to admonish a poster while using the Internet (when historically the Internet was considered by many as such a low bar) strikes me as ironic. Full stop. The observation was purely whimsical.

That being said, I have been a supporter of researching on the Web, and fleshing and hashing out theories - while staving off vitriol of all sorts from devotees of conventional media - for decades. You're preaching to the choir.

I meant no offense, folks. I am here because I believe in the voracity of this vehicle - just like you. Peace.

 

[MrMagoo]

Well humour is subjective. Like a lot of research these days…

 

[Hutan]

about 5% of patients getter better with no intervention.

Although that statistic is often used in information about ME/CFS, it is based on scant evidence. The time since onset seems to have a big impact on chances of recovery - recovery seems to be common up to 2 years, and is still happening up to 3 years. If someone is taking heavy duty drugs that cause lots of side effects, that could mask a gradual recovery. When the side effects stop that could seem like a rapid recovery.

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.

Yes.

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.

Case studies are met with a lukewarm reception here too, for the same reasons that people are skeptical about the idea that you have been cured by cyclophosphamide. And that's reasonable, given the number of cures that have been promoted (lots) versus the number that actually have been proven to work (none) and the considerable harm that has been done when people get excited about treatments with serious risks. I'm grateful that you have told us about your experience though, that does take bravery, and I appreciate the care with which you have told it too.

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?

If you are willing, it would be great if you could provide more information. For example, a detailed timeline would be useful as EndME notes. If you decide that you have given enough for now, fair enough and best wishes.

 

[siobhanfirestone]

Although that statistic is often used in information about ME/CFS, it is based on scant evidence. The time since onset seems to have a big impact on chances of recovery - recovery seems to be common up to 2 years, and is still happening up to 3 years. If someone is taking heavy duty drugs that cause lots of side effects, that could mask a gradual recovery. When the side effects stop that could seem like a rapid recovery.


Yes.


Case studies are met with a lukewarm reception here too, for the same reasons that people are skeptical about the idea that you have been cured by cyclophosphamide. And that's reasonable, given the number of cures that have been promoted (lots) versus the number that actually have been proven to work (none) and the considerable harm that has been done when people get excited about treatments with serious risks. I'm grateful that you have told us about your experience though, that does take bravery, and I appreciate the care with which you have told it too.



If you are willing, it would be great if you could provide more information. For example, a detailed timeline would be useful as EndME notes. If you decide that you have given enough for now, fair enough and best wishes.

I think I tried paxlovid in spring 2023f HBOT in summer 2023, SGB in winter 2023. No effect at all from any of these.
This drug has been in a trial, my data has a correlation with lowering IgG resulting in remission - at the exact time of lowered IgG without me knowing this was the case till after when bloods had come through.
i think rapamycin was started winter 2023 - i felt improvements in brain fog after about two days but didn’t treat underlying issue nor help POTS.
A case study has minor value which is quite different from no value. I have no idea about the woowoo mind stuff around ME but from what I hear it has about 5% efficacy - similar to natural recovery rate so useless.
I also think ME is multiple things, and I’m in the autoimmune category, some may respond to different treatment and several bio markers are likely needed to help this.

 

[siobhanfirestone]

I wouldn't imply that @siobhanfirestone describing her story is useless. Every anecdote has some worth, even if only potentially as one of many anecdotes. If fifty more people post here in the next two weeks that they had the same experience with cyclo, outside of a controlled trial, that would certainly feel like evidence of something, at least in the proximity of an ME treatment, and it might perk up a researcher's ears and motivate them to do a controlled trial. Even though each anecdote individually might only be as conclusive as this one or less, I think they add to something which can have significant value.

The more inquisitive we are about this particular experience, the more "controlled" and potentially useful we can make it, in the broader scheme and the long run.

Absolutely not recommending people try this drug on their own, and there might be something to the argument that openly discussing such an anecdote presents unnecessary risk of others trying it and being severely hurt. Though I think the discussion being very clear and forthcoming about the risks of people getting injured might decrease the risk enough that it doesn't outweigh the value of the data.

Thank you, we also did a lot of bloods to try and track what was going on in order to understand it, this is important because I now am mentally preparing for it to return at some point - whilst I plan a huge trip around Africa for when my immune system has recovered!
To be clear I do NOT say this as encouragement for anyone to do this. It’s hard as nails chemo - again though chemo had nothing on the living hell that was ME/ Long Covid

 

[siobhanfirestone]

What is ME? We can receive a diagnosis of ME six months post-viral onset. I tried a treatment based on a small study on CFS patients. For most it helped improve 'fatigue'. I on the other hand went into complete relapse.

I personally want to know the pathophysiology of delayed post-exertional malaise syndrome (DEMS) before I try any treatments This is the hallmark symptom/symptoms.

@siobhanfirestone I am very happy that the treatments worked for you and that you are in remission.

One question, are you able to exercise like a normal person repeatedly?

yes fiull exercise no PEM, i went to a friends house the other day and cycled 20 miles and rock climbed. i feel liberated from PEM, no issues at all from it

 

[Karen Kirke]

Really glad you’re doing well @siobhanfirestone , long may it last. Enjoy.

For the overall scientific discussion, I think the PACE trial’s specialist medical care only participants can give a bit of perspective on what you might expect to happen to someone with moderate ME/CFS over time without treatment that actually treats the ME/CFS. I downloaded the data when it was publicly available. Participants in the specialist medical care only group had an average of 5 sessions with a doctor specialised in ME/CFS.

Physical function scores – specifically, short form 36 physical function subscale scores – give a decent idea of how severe someone is. 100 is best; someone with a score of 100 is “not limited at all” in “Vigorous activities, such as running, lifting heavy objects, participating in strenuous sports”, and not limited at all in any of the other, easier activities either. Someone with a score of 95 is limited a little in vigorous activities but not limited at all in moderate activities “such as moving a table, pushing a vacuum cleaner, bowling, or playing golf” and not limited at all in any of the other activities in the scale e.g. walking several blocks and climbing several flights of stairs. Someone with a score of 90 is limited a lot in vigorous activities but not limited at all in moderate activities or any other activities on the scale. So they’re able for as much moderate exercise as they want but not able for running/similar.

We can use van Campen’s categories of mild ME/CFS (SF36PF 60-100), moderate (SF36PF 30-59) and severe (SF36PF 0-29) (see table 4 in van Campen 2020: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551321/). There’s been mention of 4000 steps and that sounds about right for moderate: 84% of van Campen’s moderate patients had step count of 3500–6250 (table 3).

The PACE trial’s specialist medical care only group had 98 patients with baseline SF36PF 30-59, i.e. 98 likely-moderate patients. If we divide the moderate category into two groups, upper moderate (baseline SF36PF 45-59) and lower moderate (baseline SF36PF 30-44), we can see how frequently people moved up to the mild or normal category (SF36PF of 60-100) after 1 year:
· Upper moderate: 59% of those with baseline SF36PF 45-59 in the PACE trial’s medical care only group improved to an SF36PF of 60-100 (mild or normal) by 1 year.
· Lower moderate: 31% of those with baseline SF36PF 30-44 in the PACE trial’s medical care only group improved to an SF36PF of 60-100 (mild or normal) by 1 year.

If we look at the whole moderate category again:
· 57% of those with baseline SF36PF 30-59 in the PACE trial’s medical care only group improved by 10 or more points on the SF36PF by 1 year. 10 or more points is frequently used as a cut-off for clinically meaningful improvement (validity debatable).
· 38% improved by 20 or more points on the SF36PF by 1 year.
· 22% improved to an SF36PF ≥ 75 at 1 yr.
· 6% improved to an SF36PF ≥ 90 at 1 yr.

It would be nice to know how these people did over time but we don’t have individual-level data for the long-term follow-up that was done. There is individual-level data at both 1 year and 2-5 years for a handful of patients who were moderate at baseline (i.e. SF36PF 30-59) and attended NHS clinics during the GET/CBT/activity management years. These are Collin & Crawley 2017’s “former” patients, data publicly available:

· 11 patients had an SF36PF≥75 at 1 year (11/103, 10.7%), 5 of whom remained at that level at 2-5 years.
· 3 patients had an SF36PF≥90 at 1 year (3/102, 2.9%), 2 of whom remained at that level at 2-5 years.

The PACE trial’s specialist medical care only participants had been ill for a median 25 months (the median for the overall trial was 32 months). Collin & Crawley’s patients above had been ill for median 36 months. These illness durations are for the groups as a whole, not for moderate patients only.

Here’s my summary, all predicated on PACE participants being reasonably representative of the ME/CFS population (not a given):

· For a person who starts off with moderate ME/CFS and has some medical attention, being able to do unlimited moderate exercise or better one year after treatment begins is rare, but it happens for some without any treatment that you’d expect to dramatically affect ME/CFS.

· Improvement from moderate ME/CFS to a much better level of physical functioning by 1 year is not rare at all (see 38% improving by 20 or more points on the SF36PF and 22% improving to SF36PF≥75 above).

· Some improvement in physical functioning overall is the norm among moderate patients receiving some medical attention, even when that treatment would not be expected to improve physical functioning.

 

[siobhanfirestone]

Really glad you’re doing well @siobhanfirestone , long may it last. Enjoy.

For the overall scientific discussion, I think the PACE trial’s specialist medical care only participants can give a bit of perspective on what you might expect to happen to someone with moderate ME/CFS over time without treatment that actually treats the ME/CFS. I downloaded the data when it was publicly available. Participants in the specialist medical care only group had an average of 5 sessions with a doctor specialised in ME/CFS.

Physical function scores – specifically, short form 36 physical function subscale scores – give a decent idea of how severe someone is. 100 is best; someone with a score of 100 is “not limited at all” in “Vigorous activities, such as running, lifting heavy objects, participating in strenuous sports”, and not limited at all in any of the other, easier activities either. Someone with a score of 95 is limited a little in vigorous activities but not limited at all in moderate activities “such as moving a table, pushing a vacuum cleaner, bowling, or playing golf” and not limited at all in any of the other activities in the scale e.g. walking several blocks and climbing several flights of stairs. Someone with a score of 90 is limited a lot in vigorous activities but not limited at all in moderate activities or any other activities on the scale. So they’re able for as much moderate exercise as they want but not able for running/similar.

We can use van Campen’s categories of mild ME/CFS (SF36PF 60-100), moderate (SF36PF 30-59) and severe (SF36PF 0-29) (see table 4 in van Campen 2020: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551321/). There’s been mention of 4000 steps and that sounds about right for moderate: 84% of van Campen’s moderate patients had step count of 3500–6250 (table 3).

The PACE trial’s specialist medical care only group had 98 patients with baseline SF36PF 30-59, i.e. 98 likely-moderate patients. If we divide the moderate category into two groups, upper moderate (baseline SF36PF 45-59) and lower moderate (baseline SF36PF 30-44), we can see how frequently people moved up to the mild or normal category (SF36PF of 60-100) after 1 year:
· Upper moderate: 59% of those with baseline SF36PF 45-59 in the PACE trial’s medical care only group improved to an SF36PF of 60-100 (mild or normal) by 1 year.
· Lower moderate: 31% of those with baseline SF36PF 30-44 in the PACE trial’s medical care only group improved to an SF36PF of 60-100 (mild or normal) by 1 year.

If we look at the whole moderate category again:
· 57% of those with baseline SF36PF 30-59 in the PACE trial’s medical care only group improved by 10 or more points on the SF36PF by 1 year. 10 or more points is frequently used as a cut-off for clinically meaningful improvement (validity debatable).
· 38% improved by 20 or more points on the SF36PF by 1 year.
· 22% improved to an SF36PF ≥ 75 at 1 yr.
· 6% improved to an SF36PF ≥ 90 at 1 yr.

It would be nice to know how these people did over time but we don’t have individual-level data for the long-term follow-up that was done. There is individual-level data at both 1 year and 2-5 years for a handful of patients who were moderate at baseline (i.e. SF36PF 30-59) and attended NHS clinics during the GET/CBT/activity management years. These are Collin & Crawley 2017’s “former” patients, data publicly available:

· 11 patients had an SF36PF≥75 at 1 year (11/103, 10.7%), 5 of whom remained at that level at 2-5 years.
· 3 patients had an SF36PF≥90 at 1 year (3/102, 2.9%), 2 of whom remained at that level at 2-5 years.

The PACE trial’s specialist medical care only participants had been ill for a median 25 months (the median for the overall trial was 32 months). Collin & Crawley’s patients above had been ill for median 36 months. These illness durations are for the groups as a whole, not for moderate patients only.

Here’s my summary, all predicated on PACE participants being reasonably representative of the ME/CFS population (not a given):

· For a person who starts off with moderate ME/CFS and has some medical attention, being able to do unlimited moderate exercise or better one year after treatment begins is rare, but it happens for some without any treatment that you’d expect to dramatically affect ME/CFS.

· Improvement from moderate ME/CFS to a much better level of physical functioning by 1 year is not rare at all (see 38% improving by 20 or more points on the SF36PF and 22% improving to SF36PF≥75 above).

· Some improvement in physical functioning overall is the norm among moderate patients receiving some medical attention, even when that treatment would not be expected to improve physical functioning.

two important points that i think render this data sadly not very relevant

1) PEM of 12-72 hours was not diagnostic criteria. therefore in my experience it could be a bunch of things that make people "tired", not post viral disease.

2) Improvement is not remission, and remission as others have said should be a life with no symptoms but most importantly no PEM, if your trial doesnt hyper focus on that its redundant in my opinion. Even at bbest thats 2% who p[otentially had remission in this trial, which is even less than expected

 

[Jaybee00]

Physical function scores – specifically, short form 36 physical function subscale scores – give a decent idea of how severe someone is.

I don’t agree with the use of SF 36 10 physical function questions. I basically score 90 on the 10 PF questions so I would score as not disabled or normal. The problem for me is that the disabling aspect my disease is brain fog, and general fatigue/vitality. So using the 10 PF questions on me would really tell you nothing about my disease/disability.

Here is the full SF 36— the PF questions are 3-12, 0,5,10 scoring.

https://clinmedjournals.org/articles/jmdt/jmdt-2-023-figure-1.pdf

 

[Karen Kirke]

I don’t agree with the use of SF 36 10 physical function questions. I basically score 90 on the 10 PF questions so I would score as not disabled or normal. The problem for me is that the disabling aspect my disease is brain fog, and general fatigue/vitality. So using the 10 PF questions on me would really tell you nothing about my disease/disability.

Yes, the SF36PF only measures physical function, which is relevant in this thread where return to exercise and step count are being mentioned (validly) as evidence of remission, and where we’re looking at people who started off with SF36PF scores of 30-59 and ended up ≥ 90. Their physical disability has reduced, but that does not imply that they feel well or that their cognitive functioning has returned to normal. We can't just say that someone with a score ≥ 90 is normal or does not have ME/CFS. I spent a bit of time in that range and did not feel well for a lot of it, so I hear you.

We know there are people with SF36PF ≥ 90 who are unwell enough to seek treatment – in Collin & Crawley’s data there were small numbers of patients who had SF36PF ≥ 90 at baseline in both of their cohorts. There will be many more operating at that level and not seeking treatment.

 

[MEMarge]

I'm so pleased that you are doing well @siobhanfirestone and many thanks for posting your treatments info on here.