Friday, 22 January 2016

What is Autologous Heamatopeitic Stem Cell Therapy

There is a lot of interest in AHSCT because  of the panorama programme this week but what is it. You will have heard of it on the TV programme but you will not have been told what it involves. 

The problem is this means many different things and many ways to do this are used, which makes it difficult when you are trying to assess risk verses benefit. 

There are two main types (a) myoablative and (b) non-myoablative.
The aim of the (a) myoablative is to replace your immune system whereas (b) is to re-boot your immune system and so is the ultimate immunomodulator

Autologous Blood Stem Cells
First of all the infusions are with your own cells (autologous) because if they were from someone else when they arrive they would reject your organs and cause graft-verses host disease.

Autologous HSCT requires the extraction of haematopoietic stem cells (HSC) from you and storage of the harvested cells in a freezer. The person with MS is then treated with high-dose chemotherapy at the cost of partial or complete bone marrow ablation during myoablative treatment (destruction of patient's bone marrow's ability to grow new blood cells). The pwMS own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the pwMS normal blood cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment since the recovery of immune function is rapid. Also, the incidence of pwMS experiencing rejection (graft-versus-host disease) is very rare due to the donor and recipient being the same individual. 

Haematopoietic progenitor cell antigen CD34 is a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells.Cells expressing CD34 (CD34+ cell) are normally found in the umbilical cord and bone marrow as hematopoietic cells

These stem cells do not turn back the MS clock to make new nerves and myelin. These are the stem cells and their job is to regrow white blood cells and they are not the type of stem cells that are going to make new nerves or new myelin. Therefore you cannot expect the treatment to replace lost function. One hopes that it stops any more attacks by the immune system and stabilises the disability or if the treatment is occurring during disease activity, it stops that activity so that the bodies own repair mechanisms are allowed to work and the inflammation is removed such that there is improvement. Please note this is not really repair of established disability it is driving the inflammatory response into remission

Lower dose cyclophosphamide  and filgratim is used to get the stem cells out of the bone marrow and into the blood. These are  frozen down and then you get the immune abalation.

Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the proliferation and differentiation of granulocytes. In somes cases granulocyte-macrophage colony-stimulating factor (GM-CSF), also called sargramostim and molgramostim.GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells.
Then comes the therapy this is the immune depletion. One approach is myoablation and this may use a combination of drugs and may use BEAM (Carmustine, Cytarabine, Etoposide, Melphalan) chemotherapy protocol which is administered over a period of six days often with the addition of anti-thymocyte globulin (T Cell depletion) for a couple of days as supplementary rather than essential lymphoablation.

Carmustine (bis-chloroethylnitrosoureaBCNUBiCNU) is a medication used mainly for chemotherapy and sometimes for immunosuppression before transplant. It is a nitrogen mustard β-chloro-nitrosourea compound used as an alkylating agent. As a dialkylating agent, BCNU is able to form interstrand crosslinks in DNA, which prevents DNA replication and DNA transcription so it kills dividing cells.

Cytarabine or cytosine arabinoside (Cytosar-U or Depocyt) is a chemotherapy agent used mainly in the treatment of cancers of white blood cells. It kills cells by interfering with DNA synthesis.It is called cytosine arabinoside because it combines a cytosine base with an arabinose sugar. Cytosine normally combines with a different sugar, deoxyribose, to form deoxycytidine, a component of DNA. Cytosine arabinoside is similar enough to human cytosine deoxyribose (deoxycytidine) to be incorporated into human DNA, but different enough that it kills the cell. 
Etoposide or VP-16 (trade name Etopophos) is a cytotoxic anticancer drug which belongs to the topoisomerase inhibitor drug class.:

Melphalan is a chemotherapy drug belonging to the class of nitrogen mustard alkylating agents.
This chemical alteration inhibits DNA synthesis and RNA synthesis, functions necessary for cells to survive. These changes cause cytotoxicity in both dividing and non-dividing cells
This destroys the immune system and if you do not get stem cells to replace your immune system you cannot fight infection and there is a risk of a lethal infection.

However the non-myoablative therapy does not eliminate your immune system and this is what is being proposed as a treatment.

The  treatmement is not the stem cells the treatment are the immune depleting agents.

This treatment uses a combination of drugs one used is alemtuzumab (T and B cell depleting), others use rituximab (B cell depleting), others use anti-thymocyte antibody ( T cell depleting). They are often used in combination with high dose cyclosphosphamide.Cyclophosphamide  is an alkylating agent of the nitrogen mustard type. An alkylating agent adds an alkyl group to DNA. It attaches the alkyl group to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring. This interferes with DNA replication

Adverse drug reactions from cyclophosphamide include chemotherapy-induced nausea and vomiting, stomach ache, haemorrhagic cystitis, diarrhea, darkening of the skin/nails, alopecia (hair loss) or thinning of hair (in the BBC programe people lot their hair), changes in color and texture of the hair.

With this treatment the immune system reboots as occrs with alemtuzumab and cladribine. However you do not need stem cells for treatment and the immune system will regenerate with time.

However in non-myoablative HSCT, CD34+ stem cells are transplanted to more rapidly repopulate the body with Neutrophils, which are our first line defense against infection. These are further stimulated with Filgrastim (G-CSF) or GM-CSF. Neutrophil granulocytes are the most abundant (40% to 75%) type of white blood cells in most mammals. They form an essential part of the innate immune system. This repopulation takes about 20 days and this is when you are most at risk from infection. T cells and B cells will take longer to regenerate.

So the idea that this is a stem cell therapy is rather misleading , it is just a very aggressive form of immunosuppression. 

Is this the most aggressive immunosuppression, the answer is no because myoablative is more aggressive and you need to re vaccinate yourself when you repopulate you immune system. 

However, which combination is optimum and do you need to deplete your innate (neutrophils and monocytes) system. Dogma would say no...unless you are certain type of mouse EAEer where there is a view that neutrophils are the important cell type. 

Therefore are you simply inducing side effects and not really targeting any thing extra. Although using stem cells may help in the re-booting process but this is not their function and the immune cells causing MS may not all be destroyed and relapses can occur.

The people doing the HSCT trials state a 1% mortality rate on their websites, but the trials indicate this risk may well be much lower  

I would say yes there is something different and that is because cyclosphosphamide and the phosphorylated form of cyclosphosphamide enters the brain, unlike current DMT. However could this be achieved by drugs that are less toxic than cyclophosphamide.

What are the problems with the trials.

When the trials were started in 2006 the landscape was very different, there were few treatments available and most of them were not very effective, natalizumab had been shown to be risky.

Alemtuzumab (and Ocreluzimab and Movectro) were not around

The trials are unblinded and the investigators are openly saying that the treatment works. The lack of blinding in the Alemtuzumab was critisized by the FDA, but there is no randomisation, no blinding and the investigators are helping to create the placebo effect. 

The HSCT treatment uses multiple drugs to deplete the immune system so you can imagine that two is better than one. One can argue that there is an 80% reduction in disease activity shows that this is the most effective. I can agree with this, but this group is a selected group of active pwMS.

 Some may have  failed with a "big gun drug" and get the treatment option on a compassionate basis but in the trials Alemtuzumab is an exclusion criteria. 

However people may say there is no evidence that it is really any better than other effective treatments.  This I suspect will be argued by opponents of HSCT and this argument cannot be countered because this has not been tested. 

It would need a head to head trial of AHSCT verses Alemtuzumab (currently) or ocrelizumab (in the future). 

If it takes until 2020-2022 to finish the trials and go to the regulators, the landscape may be different as some treatments may be out of patent and the cost constrainst will work against the cost-effectiveness. Will it get third line approval, as it is used now, or will it get first line  useage

HSCT induces secondary Autoimmunity
People may also say that I don't want the autoimmunity associated with Alemtuzumab, but this is occurring in HSCT also.

This includes ITP. People treated with Alemtuzumab are screened every month to detect this for up to 4 years after their treatment. Is this occurring following HSCT? Certainly the people doing health tourism are not getting follow-up treatment from their treating physician. Therefore ensure that you are followed up properly to mitigate this risk

In the Burt et al study in 2015

"Immune-mediated thrombocytopenia (ITP) developed in 3 of 22 (14%; 95% CI, 3%-35%) patients treated with alemtuzumab compared with 4 of 129 (3.1%; 95% CI, 0.9%-7.8%) patients treated with antithymocyte globulin (P = .07). Drug-free remission of ITP occurred in all cases after transient treatment with corticosteroids and intravenous immunoglobulin or rituximab.


Hypothyroidism was present in 9 patients (6.2%; 95% CI, 2.9%-11.4%) before receiving HSCT. After transplant, 7 additional patients developed hypothyroidism or hyperthyroidism. For patients with normal thyroid function before HSCT, thyroid dysfunction developed post-transplant in 2 of 20 treated with alemtuzumab (9%; 95% CI, 1%-32%) and 5 of 122 treated with anti-thymocyte globulin (4.0%; 95% CI, 1.3%-9.3%) (P = .26). The incidence rate of posttransplant immune dysfunction (ITP, hypothyroidism, or hyperthyroidism) was 22.7% (95% CI, 7.8%-45.4%) in 5 of 22 patients receiving alemtuzumab compared with 6.9% (95% CI, 3.2%-12.7%) in 9 of 129 patients receiving anti-thymocyte globulin (P = .03).

So are the risks any different.

46 comments:

  1. Excellent overview MD. Thank you.

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  2. Thanks MD for taking the time and trouble to research and write this post. I've read it through twice this morning and feel I have been thoroughly educated over breakfast! Coffee has gone cold though ;-)

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  3. As far as know, ATG (thymoglobulin) has completely replaced alemtuzumab as a anti-T-cell agent in many HSCT health centers. (B-cells are seemingly effectively destroyed by the cyclophosphamide part of the conditioning).

    According to the Burt's data cited above that change should drive thyroid autoimmunity to the levels much lower than in alemtuzumab monotherapy.

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    1. The dose used was the high dose and this has now been removed and understandably too if one wants to avoid autoimmunity, but the cost has soared. It will be interesting to look longer term as the incidence of alemtuzumab goes up to about 50% in non-HSCT above it is 22% at the time looked at, will the 7% increase also.

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    2. Alemtuzumab is not going to be used anymore and the low incidence of autoimmunity in HSTC may increase if the data with alemtuzumab is anythingto go by.

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  4. Most patients in Australia who are travelling to experienced facilities abroad (Chicago, Moscow, Israel, Mexico, Singapore) for HSCT organise a haematologist to perform their follow up care. This includes anti-virals & Bactrim as well as all relevant blood tests. Please give at least some pwMS credit for undertaking their own research & arranging a team of medical specialists to monitor them on their return. Not everyone rushes off blindly & hands over tens of thousands of dollars on the basis of positive anecdotal evidence.

    We read the published evidence, analyse the theory behind the procedure (to the best of our ability) & consult with specialists in several fields (particularly haematology & neurology).

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    1. while i really appreciate this post, this answer sounds sarcastic. in case it's not an internet translation issue, and at the risk of being a useless grammar nazi again, i just want to point out that ahsct stands for Autologous Heamatopeitic Stem Cell TRANSPLANT, not Autologous Heamatopeitic Stem Cell THERAPY. My apologies if I misread the sarcasm in the reply :)

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    2. AnonymousFriday, January 22, 2016 10:36:00 am. I couldn't agree more. And for those who have HSCT and neuros on their return without referral to a heamo, I suggest the fault lies with the doc not the patient. I have heard anecdotal stories of overseas HSCT recipients from country Australia where there is only one neuro available who refuses to treat them post HSCT. I have heard neuros tell patients they will come back in a body bag. Why all this sarcasm and a war of worlds?

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    3. Presumably if a UK pwMS goes off to lets say Moscow for HSCT then comes back to the UK and subsequently and unfortunately develops problems associated with the procedure, the NHS picks up the tab for the treatment of these complications?

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    4. I'm Australian and have a somewhat different system. Considering I paid aud$68k for the treatment and associated costs by withdrawing part of our super under compassionate grounds and was taxed 22% on the sum for the privilege and have paid the $68k after 8 years of full time work and paying taxes, I have to say I have absolutely no issue with a person coming back from Moscow and whatever country of their residence picking up the tab for any complications. I mean, come on.

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    5. "..the NHS picks up the tab for the treatment of these complications?"

      Is that a question? If the UK pwMS goes of to Moscow for HSCT will the NHS pick up the cost for monitoring the disease or they won't act until a problem occurs? That would be my question.

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    6. MouseDoctor2Friday, January 22, 2016 3:46:00 pm also if I understand your logic correctly, then we could also debate whether suicide victims should be treated and who should pay for that treatment.

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    7. Maybe it is time to start Tranpslant Saturday.

      Dear Bojana you don't need to use the Troll font. I am well aware that it is termed transplant, but I am also aware every time someone says transplant them some one says its not really a transplant because you are using your own cells. EAE used to be Allergic it is now Autoimmune...doesn't therapy sound better than transplant?

      Why not use it and we can can start a trend.

      Well without wanting to be sarcastic but can a suicide victim be treated becuase if they are a victim have they not suceeded in their suicide.

      As to NMD2 it was a question...yet such hostility today. I'm sure the NHS will come to the resue because thats what they do. Infact I know we are doing this right now.

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    8. Yeah the NHS cover the cost of monitoring/follow-up if you need them to. And so they should. It's a disgrace I had to pay for the treatment myself in the first place. Plus I've saved them an absolute fortune in MS drugs.

      Still, at least that leaves more in the pot for homeopathic potions, or whatever else they rinse my taxes on.

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    9. I think MD2 has a good point. If a person has more money than sense and wants to go overseas for medical tourism they should also be responsible for their own monitoring for any issues related to the treatment. After all this was your choice.

      For those that have aggressive disease HSCT may be an option and a trial is a way to get this treatment, and this is what this therapy is being evaluated for if it becomes approved in the future.

      http://www.ncbi.nlm.nih.gov/pubmed/19773265

      But those who are newly diagnosed, have never tried an approved therapy and think they know what's best I would say good luck and I hope you take complete responsibility for your decision.

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    10. MD2 was asking a quesstion.

      I suspect people are spending the money they can ill afford and if you put all your money into buying an Aston Martin, when you have a crash should we say sorry we are not treating you because you spent money on a fast car when you should have spent it on a caar with more air bags.

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    11. Not sure how many HCT trial centres ther is in the UK

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    12. HSCT was something that was originally trialed for the worst of the worst, then it was trialed for those with highly aggressive disease and lastly those who failed at least one conventional therapy yet still had signs of inflammation (Burts trial is the last category). HSCT may have been a panacea when there was just Copaxone and Interferons, but in this day and age it is looking less and less ideal with so many immunosupressants flooding the market and many more to come.

      So why spend your money on HSCT at an overseas clinic? Its because it has been toughted that it is the only way to stop progression. You have to hit hard and early. Team G is part of this mindset.

      But in reality this is only applicable to a small set of MSers.

      Also, to equate buying a sports car to that of buying a treatment that has been hyped to be the only thing to stop the disease is a pi$$ poor analogy.

      MSers who want HSCT overseas is their choice but they should also be aware of the consequences.

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    13. Anon.

      Let’s start with this point shall we (I'll come onto your second post in a moment)…

      “If a person has more money than sense and wants to go overseas for medical tourism”

      You and your condescending, petty insults... I would say such childishness is beneath you, but we both know sadly it is not.

      However, let’s see the rest of your post through, in case you’ve turned a corner in forming a coherent argument/point of view…

      “If a person has more money than sense and wants to go overseas for medical tourism they should also be responsible for their own monitoring for any issues related to the treatment. After all this was your choice.”

      Oh dear – not looking good is it? How very, very sad. It must be pretty desperate to live in your head.

      Nevertheless, let’s see this through to its logical conclusion:

      - If a person is overweight through diet, that is their choice. Do you contend that they should also be responsible for any medical issues arising from their choice, and thereby be cast aside by the NHS?
      - How about former drug users?
      - Those who don’t exercise enough?
      - People who’ve smoked at some point in their lives?
      - People who enjoy a sun tan?
      - Those who like a drink?
      - I mean, how far do you take it? What if someone has complications during childbirth; Should they be responsible for their own monitoring and any associated issues, for choosing to have kids?

      Or perhaps your vitriol is only aimed at those who put themselves at (in your distorted view) unnecessary risk *overseas*.

      Only those traitors should be cast out of receiving medical care from the system they’ve funded, through their taxes, for their entire working lives – whilst you, Anon, as an obvious paragon of virtue – are deserving of having your Copaxone (or whatever) funded by the rest of us nonetheless. Sounds reasonable right? (Lols)

      Obviously, you are absolutely entitled to your opinions – and it’s good that you air them on here as it gives a fascinating insight into what happens to kids who were bullied at school.

      Fortunately for the rest of us, we live in a society where such xenophobic little Hitler’s are generally ignored/carry no influence.

      Happy trolling though.

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  5. MD - a very good and informative read. Can I ask why a comparison between the Alemtuzumab trials/effectiveness vs the published trails for HSCT (non-mylo) can be used to gauge effectiveness? What is the 2/3/5 year success rate is the two when measures side by side?

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    1. I started to compare the Burt et al. 2015 trial data with the phase II data (loaded with highly active) but saw the outcomes were different the starting for the Burt trial was EDSS 4 verse EDSS 2 and this will take time. But if we compare alemtuzumab phase II to CARE I alemtuzumab phase III then it is not as good.

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  6. "I would say yes there is something different and that is because cyclosphosphamide and the phosphorylated form of cyclosphosphamide enters the brain, unlike current DMT."

    I hear this a lot on this blog. The notion that because a drug can cross the blood brain barrier is an indication that it is more effective is what is being suggsted.

    However there are no cases where HSCT (myeo, non-myo, using TBI, etc.) has been able to eliminate oligoclonal band.

    The only way this is suspected to be achieved is by using allogenic HSCT where the donor cells eliminate all of the immune cells through GVH mechanisms. Talk to researcher at the Fred Hutchinson Cancer center if you want their take on it (they are researching allogenic HSCT for MS).

    So if B cells in the CNS are part of the mechanism of MS, autologous HSCT has no effect.

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    1. It is not a guarentee of greater efficacy if a compound gets into the CNS it depends on the mechanism of action if the plasma cells are not dividing or dividing quick enough then it does not matter how much gets into the brain.

      However to say that all the issues of immune response in the brain is due to plasma cells is an over statement. There are plenty of examples where delivering drugs into the CNS improves efficacy, including our own work and work of others

      http://www.ncbi.nlm.nih.gov/pubmed/19605531

      If the action is to stop white cells getting in the brain then it is irrelevant to how much gets in the brain. If the action is to stop microglial function then it is critically important

      "If B cells in the CNS are part of the mechanism of MS, autologous HSCT has no effect"...so is this why the effect on progression is debateable?


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    2. I'm jumping on this comment because I had some questions. Have a background in viral infection, but MS is new to me. Feel free to just direct me to review articles if these are obvious.

      So, the cyclosphosphamide does cross the bbb, but will the mabs targeting B cells get into the CNS? If not, is that OK? Do the plasma-cells within the CNS not re-open the BBB from the inside to generate a second autoimmune response, or is the hope that this is a slow process, and ablation outside the CNS restarts the clock in some way?

      To me a non-myeloablative protocol must assume a cross-presentation form of autoimmunity, and that there's no incorrectly activated myeloid APCs, is that reasonable? Is there a consensus that the initial or driving APC events are driven by a rare event, so that it won't happen again?

      Last, given that EBV infection seems to precede MS... Is there a non-B cell reservoire of EBV in the body, an EBV vaccine, or should people getting myeloablative or non-myeloablative therapy not be treated with anti-virals indefinitely?

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    3. I don't think cyclosphosphamide is a monoclonal antibody but rather it is a drug used in chemotherapy in the past for certain cancers. It does not have a specific target like a monoclonal antibody does.

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    4. >I don't think cyclosphosphamide is a monoclonal antibody but rather it is a drug used in chemotherapy in the past for certain cancers. It does not have a specific target like a monoclonal antibody does.

      From the text:
      >This treatment uses a combination of drugs one used is alemtuzumab (T and B cell depleting), others use rituximab (B cell depleting), others use anti-thymocyte antibody ( T cell depleting). They are often used in combination with high dose cyclosphosphamide

      Does that make sense? The Non-myeloablative therapy is a combination of mabs and a small molecule.

      Either way, does not address the substance of my questions. I'm looking to solicit responses from folks with a significant background in the relevant literature. Cheers!

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    5. "So, the cyclosphosphamide does cross the bbb, but will the mabs targeting B cells get into the CNS?

      Monoclonal antibodies are huge molecules so obviously they do not cross the BBB. From your statement it sounds as though you are confused.

      Hopefully someone can answer your question.

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    6. Thanks for this info...also some studies use clorfarabine which is another oral cladribine me too. Clad can inhibt OCB in some studies

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  7. "so is this why the effect on progression is debateable?"

    Maybe so. I guess this is the billion dollar question. If oligoclonal bands are related to progression the answer is yes.

    I think though that the researchers at "The Hutch" are actually trying to replace a person's immune system through allogenic transplantation (while reducing the mortality rate).

    This is a true immune system reset. Autologous HSCT in either form is nothing more than intense immunosuppression in my view.

    So if this is the case I don't see a future for autologous HSCT with more potent and safer immunosuppression therapies set to be available in the near future.

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    1. "near future" and the timing of MS is the problem for many choosing HSCT

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  8. Re: "...... it stops that activity so that the bodies own repair mechanisms are allowed to work and the inflammation is removed such that there is improvement." If stopping inflammation enables endogenous repair then why would this not be the case in progressive disease? If RRMSers have functional disability i.e. motor impairments, bladder issues etc. then see improvement in EDSS after treatment I assume they improved via regenerative mechanisms. How else would they improve if not by regeneration?

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    1. In progressive MS things may well be too far advanced, there is a significant population of activated microglia for example that are likely to drive progression which should be untouched by immune system depletion.

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    2. Re: systemic inflammation within the BBB as a driver of neurodegeneration. If the activated lymphocytes are no longer solely responsible for inflammation, what maybe contributing to this microglial activation? Are we closer to therapies targeting activated microglia?

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  9. I'm going to try not to get into any skirmishes today :) - but, as a point of order regarding OCBs, it is not true to say that there are no cases where HSCT has been able to eliminate oligoclonal bands.

    See below from the Swedish HSCT study for MS (this was an autologous transplant cohort, predominantly BEAM but some received Cy/ATG instead). Not only did a significant number of patients see OCBs resolve, but the mean IgG index in the patients who still had OCBs was significantly lower post HSCT.

    "Analysis of the CSF

    All patients who were examined prior to HSCT (n=26) had oligoclonal
    bands in the CSF. The mean value of the IgG index
    was 0.81 (±0.24). Sixteen patients were examined after HSCT,
    11 (69%) retained oligoclonal bands in the CSF. The mean IgG
    index post-HSCT was significantly lower in comparison to the
    pre-HSCT value in those patients (0.85±0.25 vs 0.63±0.12,
    p=0.0007)."

    http://www.akademiska.se/global/adm/kommunikationsavdelningen/dokument/jnnp-2013-307207.full.pdf

    The sample size if obviously small but, nevertheless, elimination of OCBs occured in 31% of the patients tested.

    Would be interesting to be able to be able to drill down into the data on this to understand whether it was influenced by protocol/disease type/disease duration, etc. (preferably in a larger cohort).

    I wonder whether Prof Burt (or Prof Sharrack) are tracking this in their data... Would be useful to track over a couple of years as well to see what happens. I guess many patients aren't up for another/multiple LPs, which I can't blame them for, but it seems an important question needing an answer...

    I believe with Tysabri there are a number of recorded cases of OCBs resolving but that the effect is not seen until a few years after treatment commences. How long post-HSCT should we look to ensure we're not missing any effect?

    The few HSCT studies I've seen that look at this (and there aren't many) test it at either the 6 or 12 month mark post transplant, and the sample sizes are usually a) tiny and b) severe/late stage/salvage patients - purely because that's who was eligible for the trials at that time.

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    1. That may be the case for this single center, observational unlbined, non-rondomize study but regardless, of all the MS drugs or therapies used to treat MS (approved or not), the IGg synthesis rate has never been effected.

      http://www.hindawi.com/journals/msi/2015/296184/

      Researcher at the Hutch have described long lived be cells as the cockroaches of the immune system. You can't get rid of them.

      This is why the thought that allogenic HSCT whose donor cells seek out and destroy the cells in the patients body until every last nook and cranny has been examined and the old immune system is completely destroyed.

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    2. Ummm... A single centre study that took place in 7 towns?
      [Sweden: Uppsala (19), Stockholm (14), Gothenburg (4), Umea (4), Orebro (3), Linköping (2) and Lund (2)].

      Must be a very big centre…!

      "IGg synthesis rate has never been affected"
      That's your opinion (which you're obviously entitled to). I've just provided you one such study which contradicts it. And MD1 has also suggested (above) that clorfarabine can inhibit OCBs in some studies. Jury's out...

      As to allogeneic HSCT, I’m surprised at your overnight change of heart, given that you were posting about the 30% reduction in life expectancy in allogeneic patients yesterday. Graft versus Host Disease sounds to me like a grim way to go.

      I personally don’t see how you can substantially curb those risks if that’s the very effect you’re relying on to wipe all of your own immune cells “from every nook and cranny”. Can’t have your cake and eat it.

      There’s also absolutely zero evidence that it is necessary to wipe out every single immune cell in MS. It’s not a cancer spawned from a single malignant cell as far as I’m aware.

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    3. NoI have suggested that cladribine can affect OCBin some studies, clofarabine has essentially same MOA.

      Allogeneic stem cells I believe need to be reserved for cancer and am with Matt on this one that the risks and consequences don't justifiy the means

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    4. Yes allogenic HSCT in in its in fancies as it is too dangerous at this point but if the need is to completely re-establish a new immune system to halt the progressive phase (not likely) this would be the feasible route.

      Good thing there are no overseas clinics doing this at this time to entice medical tourists, but maybe they will try to set this up for those whose progression was not stopped with autologous HSCT. It could be a new business strategy.

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    5. Allogenic transplants is a retrograde step However first question you need to ask is, Is the immune system the cause of the problem in progression, if it is not you are wasting your money and risking more.

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    6. I think the HSCT cheerleaders believe that progressive MS is still purported by the same T cells that are involved with the relapsing phase, except they have undergone episode spread. Instead of meylin as the target it is the nerves themselves.

      This is why they believe HSCT will work in progressive disease. If you want to learn more of their mindset you should join some of the Facebook groups.

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    7. Thanks but I dont have the time or energy.

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    8. Anon.

      Allo HSCT is not "in it's infancy". It's been used for decades (including tested in a handful of patients MS). It is rarely used for treatment of MS these days, as far as I’m aware.

      The method of action you are referring to, to eradicate the existing immune system, is the Graft vs Host effect; i.e. You want the grafted donor cells to attack and kill the host cells.

      The problem with this concept is that the Graft vs Host process is not self-limited to lymphocytes; It can lead to the immune system going after any bodily tissue, be it your heart, kidneys or pretty much anything else – with consequences sometimes as severe as organ failure. This is reflected in the study you (incorrectly) tried to pass off as being related to autolougous non-myelo HSCT just a few days ago. Of course, in an autologous non-myelo transplant, this has little relevance since the stem cell graft is of your own cells, rather than a donor.

      As to your second claim about "episode spread", I'm afraid you're spouting nonsense again.

      Presumably what you're actually referring to is autoimmune *epitope* (not episode) expansion. This is a genuine effect, which you can educate yourself about at the link below (Figure 1 brings it to life visually).

      Perhaps, in future, it would be a good idea to read up on what you’re talking about before you start spouting drivel:

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277672/

      Many neuro-immunologists believe expanding autoimmune epitope over time plays a role in the course of MS, but that’s a whole other debate with equally compelling arguments against it, which I can't be arsed to get into with you on here.

      However, as far as I'm aware, nobody is actually suggesting the immune system is targeting the nerves themselves. This is certainly not something put forward by any of the HSCT for MS doctors I’ve come across and, whilst I can’t rule out that you’ve come across someone online who does have this view and also happens to be a proponent of HSCT, it is certainly not accurate to extrapolate this position to the HSCT community as whole (as you have alluded to here). Poorly researched, misleading sensationalism on your part (again).

      Re Facebook groups, I would highlight that the only person on this forum who regularly refers to Facebook groups (in almost every other post you make), is you.

      If people want to discuss treatments on social media, that is there prerogative. Clearly you have a bee in your bonnet about this and, based upon your conduct and frequently condescending/insulting tone on this forum, it would surprise me very little if this vitriol ultimately traced back to your being kicked out/blocked/banned from some of these groups on FB.

      No offense, but you are hard work. People can’t be bothered. Especially if you’re being a dick about it.

      You’ve made it clear you do not believe in, or want to undergo, HSCT yourself. That’s cool – nobody cares! Not a single member of the HSCT community is telling you that you have to, nobody is selling it to you, and nobody is attempting to prevent you accessing the alternative treatment of your choice instead.

      But, on that basis, one has to ask why you dedicate so much of your time to hounding and attempting to impose your unqualified vitriol for having this treatment overseas upon those who do – under the veil of anonymity and refusing to disclose your personal stake in this discussion.

      I’m afraid this is the behaviour of a troll.

      Delete
    9. "Anon.

      Allo HSCT is not "in it's infancy". "

      Comrade Matt,

      We're talking about treating MS here.

      Delete

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