Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study,2023

Discussion in 'Other health news and research' started by Sly Saint, Sep 27, 2023.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

    Background A growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare.

    Methods We assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT.

    Results With a median follow-up time of 5.5 (IQR: 3.4–7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (±SD: 1.5) for grade 3 events and 0.06 (±SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality.

    Conclusions Treatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.

    Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study | Journal of Neurology, Neurosurgery & Psychiatry (bmj.com)
  2. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    London, UK
    This looks highly misleading to me. We were doing this in 1995 and it became clear that people did well for about five years - their median follow-up. After that the benefit looked minimal. The treatment is not in fact stem cell transplantation - which is just putting some viable cells back after the real treatment, which is ablative chemotherapy. We have moved on from making people violently ill with cyclophosphamide and the like. I wonder why anyone is raising this again now since as far as I am aware the consensus is that it was not worth it.

    And an observational retrospective study ain't good enough, as we all know.
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  3. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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  4. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

    But five years without disease is great!

    For MECFS some of the CYCLO ME patients are still cured as are some MECFS patients who received cyclophosphamide for cancer treatment.
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  5. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    London, UK
    For most of the autoimmune diseases studied we are just talking about up to five years of not getting worse. You then go back to the roller coaster of active disease with a big risk getting bladder cancer later.

    I have looked after people who got cancer from use of these drugs. It is a soul destroying business for all concerned. And then they die.

    Some ME patients who had cyclophosphamide may still be well but we do not have good reason to think had much to do with the cycle. It didn't for rituximab.
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  6. Jaybee00

    Jaybee00 Senior Member (Voting Rights)


    Most patients with relapsing-remitting multiple sclerosis (RRMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) showed no evidence of disease activity (NEDA) for 5 to 10 years, observational data showed.

    Popular article from Medpage
  7. Arvijansen

    Arvijansen Established Member

    I agree completely. One should understand that a lot of patients are already progressively severely (and violently) ill, and don’t have any choices. If we would have a plethora of options similar to diseases like Rheuma or M.S. there would be a choice. But for us it is basically choose CGT/GET and supplement X and/or suffer without any perspective for years.

    Cyclophosphamide is a strong chemo pharmaceutical, with severe side effects, especially when used in high doses. It’s used in life threatening cancer, but also auto immune conditions like R.A., lupus, where quality of life is such that it’s worth a trial.

    The CycloME trial had 50% Patients with very impressive remissions, which many patients would sign for.
    Plus 8 anecdotal cases - one really impressive compete cure from severe - which was the basis for the Norwegian doctors to start their research.

    Dosage was 600mg/m2. 4x every 4 weeks (I think)
    No patient had a structural worsening of symptoms (2 patients pulled out, so we don’t know).
    Of course, there possibly is an increased risk of cancer (but I have not found a clear study on this)


    With Autologous HSCT for MS the dosage is much higher:
    In a Russian HSCT clinic dosage Cyclo for MS patients: 100 - 200 mg/kg body weight. Or in Swedish Study 2gr/m2.
    Around 10-fold the dosage, with a purpose to ‘reset the immune system’ and then recharge your immune system with your own stem cells.
    The higher the dosage, the more increased the risks, including mortality (the last MS Study figure I read was 0,3%).

    +1000 MS patients have been going to 3 private clinics (Mexico + Russia) for more than a decade. There are some studies, specifically with fairly good results for RRMS.

    It also has been trialed with various other autoimmune diseases with varying rates of success.

    Many Long-term severe patients are capable to assess the risk, and compare +10 years of suffering life From a dark room, to a reasonable chance to A very improved life of most probably +10 years. To make a collected choice. They are already living on the edge of life.

    So considering:
    - Quality of life of severe MECFS patients is similar to severe MS patients
    - CycloME has been relatively successful (in light off most other trials)
    - I think it’s worthwhile to explore this area, esp. because lack of alternatives
    Last edited: Oct 2, 2023
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  8. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    London, UK
    The evidence is cast iron. It dates back to early use of cyclophosphamide, probably in the 1970s. Rates of subsequent bladder cancer were something like 40%. And bladder cancer is horrible and very often incurable. Think of having a treatment with a near evens chance of dying of bladder cancer? And as you say, for AHSCT the doses are very high.

    I gave up using cyclo as a rheumatologist because I saw the trade off. Andnobody gets told the reality in advance.
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  9. Arvijansen

    Arvijansen Established Member


    Indeed. Every patient has to be well informed on possible risks.
    Therefore - by lack of doctors that are treating us - we should be able to asses and check the research data ourselves.

    I did a quick search and found various studies.
    I have not found your 40%, do you possibly have a link?
    - to understand & appreciate what the 40% implies it’s important to have the complete data.

    1. this Study non-Hodgkin's lymphoma And Cyclo shows: important factor is: the higher the dosage, the higher the risk.
    https://pubmed.ncbi.nlm.nih.gov/7707439/#:~:text=For patients given cumulative doses,cancers per 100 NHL patients.

    ‘Conclusion: Cyclophosphamide-related bladder cancer is dose dependent. For patients given cumulative doses for non-Hodgkin's lymphoma between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up. At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients.’

    2. This Paper asseses much lower bladder cancer incidences


    ‘Lack of evidence strong association bladder cancer (IV Cyclo)’

    Although data from table seem considerate…:
    * 1~4% (?) after ~10 yrs
    * 2 outliers (1 study 0% + R.A. Study 8%)
    (SEE PICS)

    *Oral dosage vs Periodical IV seems to make a difference
    *Possibly also illness dependent (?)

    And: As a scientist and a doctor I understand your perspective completely.
    But unfortunately as patients we don’t have this luxury of perspective.

    For every possible therapy that has some track record we need to get into the detail to understand better the pros and cons and possible mechanisms.
    As there are not many other therapies to discuss, and neither on the close (and far) horizon.
    I m afraid the coming 5 (to 10) years there’s not much coming for us.

    Attached Files:

    Last edited: Oct 2, 2023
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