Sunday, December 29, 2013

4 Year Update - Disease still stopped

If you have come to this blog for the first time, you may find reading the following page first will be useful. . . . .

http://themscure.blogspot.com/2010/06/stem-cell-transplantation-reference.html

I'm going to keep this post very short and simple. It's been four years since my HSCT procedure and my MS is still stopped. My health has been stable and steady for the past couple of years with no use or need of any MS drugs whatsoever. Other transplanted MS patients are now well past a decade of halted disease activity, and still going strong. Clear indication that HSCT is a durable treatment. My future belongs to me and I have no regrets whatsoever having undergone HSCT to beat MS. I won and MS lost. Good riddence.

Saturday, December 29, 2012

3 year report - Hitting the wall


If you have come to this blog for the first time, you may find reading the following page first will be useful. . . . .

http://themscure.blogspot.com/2010/06/stem-cell-transplantation-reference.html

OK, don't let the title of this posting scare you. It simply means that my MS-related health has entered a stable phase with little, if any further noticeable change in my MS health status. Today is my three year HSCT "birthday" and I continue to be grateful that I have regained my future that prior to three years ago was quite uncertain. As for my current post-transplantation status, I'm pretty much the same as I was at two years post-transplantation. All this is actually nothing but good news in that my underlying MS disease activity & progression remains 100% stopped and have additionally retained the substantial improvement (50% reduction of EDSS) of my pre-existing MS symptoms. This is precisely the way Dr. Richard Burt describes what happens to many post-HSCT MS'ers in the first 45 seconds of the following video. . .

http://www.youtube.com/watch?v=msYTOSo4jZo&feature=channel
 
So what this all means is that basically, just as anticipated, I have experienced substantial symptomatic improvements in the first two years following my transplantation. And although my disease is still 100% stopped today, I haven't 'noticed' any additional improvements since my two year posting (hence the words "hitting the wall" in the title). So if you would like the details of my current status, please read my 2 year posting which is an accurate description of where I still sit today; still cured of MS and I have a reasonable expectation this will endure for the remainder of my life. It is clear to me today that based upon the accelerating progression of my pre-transplantation MS disease activity and accumulating disability, today I would be quite close, if not actually in, a wheelchair if it were not for HSCT. I'm now confident in stating that HSCT has prevented this from happening.

Overall I'm very happy that I had HSCT and am quite satisfied with the result, even if I don't experience any further improvements beyond what I have already experienced. Mainly I am still wonderfully happy today that I have no underlying MS disease activity or progression and do not take any kind of MS immunomodulator drugs of any kind. Nor do I see a neurologist any longer after having vanquished my MS. Having previously done so is just becoming a distant memory. As is the case for most people in a similar situation, I have absolutely no regrets for having undergone HSCT to cure my MS. You will only see gratitude on my face.

If you or someone you know is interested to seek HSCT to cure MS (or other hematologically-rooted autoimmune disease, of which there are many), please join our Facebook group forum "Hematopoietic Stem Cell Transplantation for MS and autoimmune diseases." There are many people participating that have already received, are planning to receive or helping someone else to receive HSCT for their respective autoimmune disorder. It is a great forum to ask questions, present information, ask or learn about how HSCT treatment can help a great number of people that are curable with HSCT treatment. It is a closed group (to lock out spammers) but if you enter your name we will approve you. Here is the site. . . .

https://www.facebook.com/groups/149103351840242/?ref=ts&fref=ts#!/groups/149103351840242/

Likely I will make a few more postings before my 4 year Birthday. For now, a Happy and Prosperous New Year wish to everyone. Be healthy!
 

Thursday, December 29, 2011

2 year report - Enduring Cure Status


Wow. It's been two years already since my HSCT procedure. I still understand the importance and significance of having undergone HSCT to cure my MS, but I think about it less these days because curing my MS has instilled normalcy to my daily function and has allowed me to move on with my life. Now that I have regained my life I think it would be a shame to continue to dwell on the way things 'used to be.' So these days more ordinary and mundane issues dominate my thinking. Things like my son's school, the job, grocery shopping and meeting with friends & family to enjoy the here-and-now. The topic and thought of MS does not rear its ugly head as it previously used to. Quite frankly, as far as my physical health is concerned, I spend far more time thinking about my cholesterol level (which I am effectively controlling) than I do about how MS has affected my life. And I'm accepting of this. For my own life I'm completely OK with MS fading from my existence. I'm glad to say that (thanks to HSCT) I have vanquished MS.

As time goes by following my transplantation procedure, it is ever more clear to me that there is no question HSCT has successfully met (and continues to meet) my expectation of what a cure for MS should be; 100% stopping of the underlying MS disease activity and progression. Since my transplantation procedure two years ago, my MS disease progression has been completely stopped. And on top of this I have also experienced significant improvement (reversal) of most of my pre-existing symptomatic manifestations. I will explain further regarding my current status in the following paragraphs. . . . .

Although I can't currently run a mile (in fact I can't run at all out of fear of falling down due to some residual foot numbness), I can walk a mile-and-a-half without stopping to rest which I could not do prior to HSCT as I was at EDSS 3.5 at that time with a maximum walking range of only several hundred meters without rest. Today post-transplantation I'm improved to EDSS 2.0 and can walk substantially further, improved to the point that with a little forethought on planning & managing my daily activities, I less often notice that my legs are slowing me down. I no longer see a neurologist (no longer necessary) and I love that I no longer take any medication or treatment of any kind for MS. No more regular injections (Avonex that I had taken for 15 years prior to HSCT). Yipee! My future belongs to me again, not a wheelchair.

Following myeloablative HSCT the human body is rendered antigen naive, causing the body to loose immune memory accumulated through a lifetime of exposure to infectious agents, environmental antigens and vaccines. This "loss of immune memory" phenomenon (immune system becoming "antigen naive") is the biggest part of the overall equation as to why HSCT stops the body's damaging autoreactivity to restore immune self-tolerance resulting in a halting of further underlying MS disease activity & progression. But also, it becomes necessary for myeloablative HSCT recipients to be re-vaccinated for diseases starting from the beginning again, just like a newborn child. The following single page summary (list as developed by the US NIH / CDC) details the required vaccinations schedule, of which I have already received the first two rounds and am now working with my primary care physician to have the third & final round completed soon. With the exception that my MS disease continues to be halted and continues to slowly improve over time, following this final immunization task I am now "officially" 100% past the Stem Cell Transplantation era of my life and I expect no surprises to pop up from here on out. (click to enlarge):

And the NIH / CDC comments on the subject of re-immunizations:

Vaccination of Hematopoietic Stem Cell Transplant (HSCT) Recipients

http://www.cdc.gov/vaccines/pubs/hemato-cell-transplts.htm

On the subject of my MS symptomatic improvement, a quantitative way to explain the change over time is to express it as an EDSS score. In all fairness, the original inventor of the EDSS scale, Dr. JF Kurtzke, had never designed, nor intended the scale to have a granular resolution finer than half-point increments. So I can legitimately claim that my EDSS improvement to date has gone from the original 3.5 to a current 2.0. However, if Kurtzke had designed the scale to have an infinite number of expressed values, then I would actually claim that today I am at EDSS 1.8. Although an unreal EDSS number, I like to think of this 1.8 number as still being meaningful in a way similar to the usefulness of the mathematical imaginary number i that is irrational, but still mathematically valid such as in the case of x2 + 4 = 0. (Perhaps I'll start referring to this as the EDSSi number.)

So to express the improvement I have so far experienced in my disability, my symptoms have reversed a total of 50% as shown in the following graph I have created to characterize the improvement I have seen over time. However, even though my symptoms do continue to improve, the change over time is significantly slowing to the point that I cannot now discern the improvement over a shorter interval of time, as opposed to the period prior to 18 months post-transplantation when I could clearly notice improvement over a shorter interval of time. It may take several more years for me to directly notice any more 'specific' improvement from where I stand now. But no stress on my part. . . . The activity and progression of my MS remains halted and I'm happy with the magnitude of improvement that I have so far achieved. (click to enlarge):
For those that are unfamiliar with the Kurtzke EDSS scale, you can read about it here on Wikipedia which summarizes it well:

http://en.wikipedia.org/wiki/Expanded_Disability_Status_Scale#cite_note-Kurtzke-0


As for a more detailed explanation of my current post-transplantation physical status, I don't want to be excessively verbose in what I write on this posting. So if you wish to read the contiguous details you can read the following (18 month status update) page, and then add to it what I have written below:

http://themscure.blogspot.com/2011/06/18-month-report-sustained-cure-status.html

First off, I have only three remaining symptoms (compared with about ten prior to HSCT) that I have the ability to detect some residual symptomatic manifestation that is left-over (unresolved) from purely pre-existing (pre-HSCT) issues (as I no longer have any further active, or worsening MS disease progression). These are:

1) Slight right-hand numbness that has improved from baseline, but I can still detect a little residual sensory deficit. This symptom doesn't bother me and is inconsequential. Although admittedly my writing is not as neat and legible as it once was before MS. But at least I have regained the ability to write with my hand that I had previously lost. The same applies to buttoning my shirt which requires some degree of feeling in the fingers to enable the required finger dexterity. I no longer have my wife fasten the buttons on my shirt for me because I have regained the ability to once again do this myself.

2) Leg weakness that has improved from baseline but still persists and becomes evident when I walk long distances. However, I'm fortunate to have experienced approximately 500% improvement of my walking distance post-transplantation.

3) Foot numbness which has also improved approximately 50% since my transplant.

These are the only symptoms today that I can notice, and only symptoms two and three have any affect on my life. I appear from the outside to now walk normally (prior to HSCT I often walked like I was a little drunk even when sober), but unfortunately the partial foot numbness prevents me from running because I would likely fall down in doing so because I lack a sufficient amount of tactile feeling feedback to command my feet in a suitably coordinated way for running that might result in injury if I tried. Oh well, I'll give running a try in several more years once more sensory feeling returns to my feet, which I suspect it might.

My leg weakness could use a little more descriptive information to understand what is happening with me post-HSCT (as is similar to many people with MS-induced leg weakness). I'm not an expert on nerves, but nerve function and action potential is actually a rather straightforward electro-chemical process in which nerve conduction is explained by chemical pathway operating mechanisms involving sodium and potassium ion channels. You can read more about it here if you're interested:

http://en.wikipedia.org/wiki/Action_potential

I also borrowed the following graph from Wikipedia via the GNU free documentation license. In its most simplistic explanation, once a nerve has been electro-chemically commanded (stimulated), the rising phase allows the conduction of signals to the desired end-muscles (in this case the legs). Immediately following the falling phase of the nerve action potential (some may say work function) undershoots the resting potential due to chemical depletion. In the case of healthy functioning nerves in people without MS (and in young people in particular), this undershoot time period (called the refractory period in which the nerve essentially ceases operating during this time period) lasts for only a very short time. But as is often the case with people that have been afflicted with MS, this refractory period in an affected muscle group does not recover quickly. When I was young I could sit and rest for just a short period of time following strenuous physical activity to recover. No more. Once fatigued, it takes a rather long period of time to fully recover my leg strength to continue on. Sometimes several hours. A residual affect of my pre-HSCT MS. (click to enlarge):

So at this point in time the only two things I would hope for to improve my post-MS physical life is to regain enough feeling in my feet to allow me to resume running once again, as well as a shortening of the (leg-associated) nerve refractory period so that I will face the fewest possible circumstances of ambulation restriction due to muscle-tiring. This is all within the realm of possibility. I will report accordingly if/when things unfold.

It is also important to note that prior to 18 months post-HSCT my pre-existing MS sympoms that remained would fluctuate in intensity over an interval of several days, or weeks. Now at two years post-transplantation my pre-existing symptomatic intensity has stabilized and my symptomatic manifestations are consistent from day-to-day. I generally don't have "up" days and "down" days. Each day is reasonably consistent with all the other days.

From now on I plan to make yearly updates regarding my post-HSCT status. However, I may make a few other postings on the related topic of HSCT to cure MS if I feel like doing so.

Last note. . . . I have so far been able to share my knowledge and experience with approximately a dozen other people that have gone on to receive HSCT for their own MS at various facilities around the world. And the good news is that I am currently communicating with approximately another dozen people that will also soon be seeking or receiving HSCT. Although I don't give medical advice, I am happy to share my info and opinions based upon what I know about HSCT as the only current cure for MS that can be had at the following locations that I am aware of (and I'm sure there are likely more treatment facilities that I am not aware of):

http://themscure.blogspot.com/2011/06/getting-into-hsct-treatment-if-you-have.html

For those that do receive HSCT to cure their MS, welcome to the club! We are still a small, but growing cadre. And I'm always happy to see another person beat their MS. Always.



Tuesday, September 6, 2011

The Next Miracle

I'm still happy to be totally & completely free of MS disease progression. When not thinking about the scientific validity of HSCT to cure MS (especially considering that currently there is nothing other than HSCT that can cure MS), it is easy to consider it a medical miracle.

But of course there are a few downsides (I prefer to call them trade-offs) to stem cell transplantation to cure MS. One of them is that for myeloablative chemo conditioning protocols (same as I received), permanent sterility is generally the rule. But I knew this going into my treatment so I planned accordingly since my wife and I wanted to have a second child. Although I'm pretty sure that I am currently completely infertile (as a result of my treatment), using some of my previously-banked sperm my wife and I underwent an in-vitro fetilization (IVF) procedure which resulted in the next miracle to present in my life, as shown in the following sonogram image (click to enlarge):

Yup, you got it. This sonogram image captured during my wife's pregnancy exam shows her 12 weeks pregnant. It took an IVF procedure to make it happen but my banked sperm came out of their cold liquid Nitrogen sleep to successfully do the job. It's a wonderful feeling seeing the baby's beating heart. I'm amazed that the doctors can quite-accurately predict the most probable date of birth. In this case it's March 10, 2012. We don't yet know the gender of the baby, but we'll be happy either way.

Note added later. . . the 33 week 3D-rendered sonogram image shows our healthy baby boy still in the womb and everything on track for our March 10 expected delivery date. We're excited to give Riki a little brother.

The main reason I share this info is to let others know that infertility following HSCT is not a hopeless situation and it can be overcome. Planning ahead, together with the application of some medical science and a little luck can return the gift of life, as it has for my wife and I. So if you need the scientific proof that it is possible to once again become a father (or mother, since women can still have a normal pregnancy following HSCT if using the right starting materials) following the sterility conferred by HSCT, look no further than this sonogram image confirming it is possible.

Just a last note. . . . I'm pretty sure I'm the first person from North America to undergo HSCT treatment outside of a study to cure my MS. I wonder if I am also the first HSCT-treated MS patient to now be expecting a healthy baby? Perhaps. But anyway, if so I'm glad to prove it can be done. Booyah!

Meet Kai Takahashi Goss. Born a little ahead of schedule, but healthy to grateful parents on Feb 23, 2012 (click to enlarge):

Sunday, July 3, 2011

18 month report - Sustained Cure Status


Future regained!


I know that a lot of people with MS will recognize this box of medication pictured here that I had forgotten about and found lingering in the bottom of my refrigerator as we were cleaning it out this past week (click to enlarge):


I post this picture mainly for my own entertainment & reminder of my previous life prior to my transplantation that completely stopped my MS disease activity & progression. I had taken Avonex interferon for 15 years prior to my HSCT procedure. Avonex, just like all the CRAB drugs only "slows" or "delays" the progression of MS symptomatic deficit accumulation by average of 30%, but does not stop the disease. As of today only HSCT can accomplish this. You'll notice on the prescription label that this box was issued in September of 2009, a few months prior to my transplantation. I used two of the four dose packs from this particular box and the remaining two dose packs have been sitting there in the bottom of my refrigerator for the past year-and-a-half. Ever since my HSCT procedure I have never again taken any MS drugs of any kind because they are no longer necessary or helpful (which is also the case with virtually all HSCT recipients). My underlying MS disease activity is gone. The curative effect of HSCT has returned to me my future because I no longer live with the uncertainty (and fear) of what might happen due to MS and the disease progression is no longer a part of my life. And have I mentioned how happy I am that after 15 years of chronic injections I no longer have to use a syringe since 2009 following my HSCT? Yeah, I think I mentioned that earlier. I don't mind to say it again though. This has contributed so much to the enjoyment of my daily life! (I get my own pleasure from acknowledging it out loud.)

So this is where you will come to understand my realistic reporting of the results of Hematopoietic Stem Cell Transplantation (HSCT) relative to my own MS-related disability. I'm not going to be overly-rosy or provide any exaggeration in the reporting of my current status. Here are a few basic facts as of today, a year-and-a-half since my transplant:
  • My underlying MS disease activity is (still) 100% stopped. No further progression, relapses or advancing MS activity whatsoever. This includes no new lesion activity on MRI scan. HSCT has unequivocally and unquestionably accomplished my primary goal of halting the underlying MS disease process and has restored immune self-tolerance to my body. An especially amazing accomplishment considering that I was in a (secondary) progressive phase of the disease in which it is virtually unheard of to improve from such a state. I currently feel better than I've felt in many years.
  • I no longer take any form of medication or treatment of any kind for Multiple Sclerosis. As of today I just take a multi-vitamin and keep an eye on my cholesterol level. It is truly amazing how much the enjoyment of my life has improved by NOT ever again having to inject interferon (Avonex) medication! I calculate that I self-injected IM (long needle!) interferon more than 750 times over 15 years. Although used to the injections, I would be lying if I said I enjoyed it. So happy that I no longer have to do this.
  • I've already had my first two of three rounds of vaccinations required for those receiving a myeloablative HSCT. I will have my final round of vaccination injections at 2 years post-transplant that includes the all-important MMR (you can read the 1 year update posting to understand more on this topic)
  • Other than curing my MS, the only other probable permanent side effects I have experienced from the chemo conditioning regimen are 1) Sterility (before my treatment I expected this to happen and I banked my sperm for the possibility that my wife and I will have another child), and 2) Something that I did not expect is that my body lost most ability to produce testosterone (leydig cell damage from the chemo) that I have been able to easily overcome by using a daily testosterone trans-dermal skin patch (Androderm) to restore testosterone levels to a normal range. This has proven to be painless, near-effortless and not-at-all inconvenient. It just costs money, but still a heck of a lot cheaper than the interferon I no longer take.
  • All of my pre-existing MS symptoms have improved (reversed), and continue to do so slowly over time. However, the rate of improvement now appears to be slowing as compared to the first year-to-eighteen month period directly following my transplantation. But in the famous words if Kirk Garrison, improvement is still improvement and this trend follows the "expected" asymptotic curve of diminishing returns over time. That basically means that I have experienced a tremendous amount of improvement in the first 12-18 months following my HSCT and now likely I will continue to see additional improvement over time, albeit more gradually from this point forward. The general shape of this symptomatic improvement curve shown here is fairly representative of what can often be expected for MS patients following HSCT (and is what I am experiencing). However I'm sure the slope & amplitude of this curve will somewhat differ for each individual based upon several factors that includes the phase of disease activity (RR, SP, PP) and relative total disability at time of treatment. (click to enlarge):
  • Of course the curve shown above is just a general theoretically predictive average curve which may somewhat differ for each individual (although the general properties of the asymptote should be consistent). Actual patient outcomes rarely follow the exact smooth-shape predictions as shown, so I have created another similar graph that more accurately reflects the reality of my own absolute symptomatic improvement (expressed as EDSS) over time. You can see that there is some level of normal daily fluctuation in the status of the symptoms that remain (mainly related to my leg strength), in which some days are a little better than others. But the adage that holds true. . . . "The worst symptomatic day today is better than the best symptomatic day just prior to my transplant." I think this graph accurately reflects this. (click to enlarge):

Here is Dr. Richard Burt explaining this general phenomenon:

http://www.youtube.com/watch?v=msYTOSo4jZo&feature=channel


To provide a seamless continuation reporting of my post-transplantation health status, I just copied the following list from my one year report posting and have added my current 18 month post-transplantation status update:

Sensitivity to heat
  • 12 month report - Completely resolved - This was one of my early symptoms that completely improved and disappeared. For years I could not stand the heat and I never felt cold, even in near-freezing weather. Prior to my transplant I could only tolerate lukewarm showers. Since my return from Germany I now love taking hot showers. And just like normal people without MS, on a cold day I feel cold. (I now wear warm jackets that I haven't worn in years.) I also am no longer afraid to venture outside with physical activity on a warm summer day. Now I can handle the heat and I now respond to temperature variations like I did before being diagnosed with MS in 1995.
  • 18 month update - OK, for this specific symptom I can add some descriptive modification. Now that we are entering some warmer summer weather here in July I now have come to better realize (for me) there is a difference between "feeling hot" and "being hot." I no longer "feel" hot in an abnormal way. Prior to my HSCT I felt hot continuously, all the time. Even when it was near-freezing temperatures outside I always wore short-sleeve shirts when everyone else were wearing sweaters & jackets. People sometimes commented to me that it seemed strange to see me sweating on a cool day. Things are different now as I can explain with a simple example that is now characteristic of my current heat-tolerance status. A few weeks ago I went to the beach with my wife and son just north of San Francisco (where it is usually never hot). The outside temperature was approximately 65F (18C) with average humidity. I laid down on a towel while my son ran around and played in the sand. Take a closer look at this photo my wife snapped of me (click to enlarge):



  • My wife was shocked and told me that in the seven years we've been married she has NEVER seen me wear a sweater AND a Jacket (I would have been sweating in the same situation prior to my HSCT). I guess this serves as confirmation that the way I "feel" in response to temperature is much like any other normal person would respond (my wife was also wearing a jacket). Here comes the important additional info. . . . However, when I actually am in a hot temperature environment (such as summer in the sun) it still adds a "little" (but noticeable) to the fatigue I feel in my legs (only). But I do have to admit that this specific "fatigue-adding" effect is nowhere near as severe as compared to prior to my transplant. So things are improved. Before it was a foregone conclusion that all of my symptoms would worsen substantially when I became heated. Now only my legs (no other symptoms) just feel a "little" more fatigue when hot, but not as badly as compared to before my HSCT.
Bi-lateral leg parasthesia
  • 12 month report - Completely resolved while at rest - This was also one of my first symptoms to disappear. For ten years prior to my transplant my lower legs never stopped tingling from the parasthesia. This used to be a 24/7 effect no matter where I was or what I was doing. However, now I no longer feel it under normal resting circumstances. Currently sometimes I do get some lower leg parasthesia following an arduous and / or physically demanding & stressful trek but resolves soon after a short rest.
  • 18 month update - Actually it is better now. I don't experience parathesia at all, ever. Even when stressed from an extended walk. The effect is 100% resolved. Nice.
Vertigo
  • 12 month report - Completely resolved - Although not a frequent occurrence, at random times I would experience the room "spinning" (previously would usually happen at least once a week, and occasionally more often when I tilted my head far backwards). This has not happened at all, not even a single occurrence since returning from Germany following my transplant.
  • 18 month report - Unchanged. 100% resolved.
Lhermitte's sign (and ocular "flashes" due to eye movement)
  • 12 month report - Completely resolved - Although it did not happen often, I did occasionally experience this phenomenon. It hasn't happened at all since my transplant and return from Germany.
  • 18 month report - Unchanged. 100% resolved.
Resting fatigue
  • 12 month report - Completely resolved - I know this symptomatic description sounds like an oxymoron. How can one feel fatigue while resting? And that is part of the insidious nature of MS. Often while just sitting and doing nothing but watching TV while sitting on the couch my body would feel exhausted like I just finished a ten mile uphill run. I hated this phenomenon because I could do nothing to escape the effect or do anything to not feel physically fatigued. But following the transplant procedure I no longer experience this type of fatigue onset. I still get fatigued when doing physically stressful things such as a very long walk, but never does it occur when I have done nothing stressful to provoke this unwarranted effect. A major improvement to the enjoyment of my daily life.
  • 18 month report - Unchanged. 100% resolved.
General fatigue
  • 12 month report - Substantially improved - My general fatigue level (especially while doing activities with physical exertion) is substantially reduced & improved. I don't know how to quantify this improvement, so I just have to provide a qualitative description. I simply don't tire and feel fatigued as much as compared with the time prior to the transplant. Another improvement that allows me better enjoyment of my life on a daily basis.
  • 18 month report - Improved further, now better than 12 month status. Again, I don't know how to quantify this so all I can do is to provide a qualitative description. It's just better.
Ataxia / balance
  • 12 month report - "Mostly" resolved - At least now I can walk without looking like I'm drunk all the time, which was a problem before the transplant. I estimate that to date these associated symptoms have improved approximately 70-80%.
  • 18 month report - Further improvement. I estimate that this symptom is now 90% - 95% resolved. I suspect after another year, or two it will be 100% resolved since this continues to slowly improve.
Hand sensory deficit & weakness
  • 12 month report - better than 75% improvement - I'm right-handed and for about three years before the transplant the weakness & (lack of) feeling in my hand(s) (especially my right hand) prevented legible writing and so I never communicated by the printed word except by using a computer keyboard. Now I can write again with pen & paper. It's nice to personally write my greeting card messages this year, although I still find that using a computer keyboard is easier (who doesn't?).
  • 18 month report - Further improvement. My hand strength & feeling is now recovered approximately 90% from worst-baseline prior to HSCT. Not completely recovered but now I can fasten / unfasten all the buttons on my shirt by myself. That was surprisingly difficult before my transplantation and I often previously asked my wife to fasten the smallest buttons (such as the cuffs) that I had the most trouble with. Don't have to do that anymore. I can take care of those myself now.
Foot sensory (feeling) deficit
  • 12 month report - Mostly still with me - My feet have been about 75-80% numb for a long time. This prevents me from balancing on one foot. Currently the numbness feeling is very slowly improving. Not fast reversal, but I can definitely notice the slight improvement. I'll report on this again over a longer period of time. I suspect the slow improvement will continue for several years.
  • 18 month report - Improved further even though still evident. It still is not quick reversal, but now I can balance on one foot "just" long enough to get my pants on while standing up. Although I still am unable to stand indefinitely on one foot, I'm happy to see this modest improvement.
Leg weakness
  • 12 month report - This is still my main symptomatic complaint that makes up the bulk of my evident MS symptoms. Although my leg weakness (especially after longer walks or physical exertion) has gotten better following my transplant, I have noticed the slowest improvement in this area of deficit. The good news is that I can walk further and stand for a longer time than before treatment without stopping & sitting to rest. So there has been improvement but it is to a much lesser degree than all of my other pre-existing symptoms. Again, I expect to see continued very gradual symptomatic deficit improvement over the next several years. I will report again as things change (or not) over time.
  • 18 month report - Still my only symptomatic complaint of any consequence (this is the only pre-existing symptom that matters to me anymore. . . . the others are now inconsequential). My leg strength and ability to to walk long distances is still limited, but I have still seen improvement. Prior to transplantation I was limited to several hundred meters walking distance until I needed to stop and rest. Now I can walk nearly two full kilometers (perhaps more?) before needing to stop and rest. That's better than a 500% improvement and has provided me the most significant benefit to my daily life. I hope to (and probably will) see further gradual improvement over the next couple of years. I still can't run a mile like I dreamed about while I was in the hospital, but it is still within the realm of possibility if this slow improvement continues for an extended period of time. But even if I am unable to do so, I'm quite happy with what I have accomplished so far.
Additional comment
  • [12 month added comment - Someone else told me that probably the reason these last two symptoms are the slowest to improve is because the nerves to these areas (legs + feet) have to travel the entire length of the spinal column and have been subject to the maximal MS damage over this extended length and hence will take a longer time for the body to repair/compensate for the existing damage. I don't know if this is actually correct but it seems to make plausible sense to me.]
  • [18 month added comment - the previous comment appears to fit the facts. I think maybe it is correct. Or at least I'm buying into the concept. (Thanks Erin!)]
EDSS score
  • 12 month report - 1 point improvement (so far) - Immediately prior to my HSCT I was at an EDSS of 3.5. Now one year post transplant I am an EDSS of 2.5. So I have now fallen into the category which neurologists consider "significant improvement" of my disease status (an EDSS improvement of >1.0). This still amazes me because people with SPMS (was me) virtually never see any improvement at all, EVER! Furthermore, the HSCT studies to date indicate that symptomatic improvement following HSCT continues for several years following the transplant. I'm now within striking distance of achieving my goal of being EDSS of 1.5 (or better) within the next couple of years. No guarantees. But if I were a betting man I'd say that it is entirely possible.
  • 18 month report - 1.5 points improvement (so far). I'm now at an EDSS of 2.0. As of today that's mathematically a 40% improvement as compared my pre-existing (pre-HSCT) status of 3.5. The rate of improvement has now noticeably slowed (as expected), but even additional slight improvement over time could eventually get me to my original goal of EDSS 1.5. If that happens in another couple, or several years, I'm golden and grateful! But no need to look a gift-horse in the mouth. I'm already satisfied & appreciative with what I have accomplished so far.

The future I lost 16 years ago when diagnosed with MS is now back. Because the HSCT procedure has completely stopped my underlying MS disease activity & progression I have regained enough certainty of the future that I can now better plan my life with my family!



Tuesday, June 28, 2011

Getting into HSCT treatment if you have MS


On this page I will not go into the well-established science indicating the superiority of
HSCT treatment efficacy for MS as compared to other treatment modalities (i.e. drug therapy) to effect curative results in those with MS. For such details please visit my scientific explanation & references page here:

http://themscure.blogspot.com/2010/06/stem-cell-transplantation-reference.html

For those people with MS that are interested to actually receive
HSCT treatment, there are a few options that I am currently aware of that I will explain about further.

The main decision that an MS patient considering HSCT
must initially make is "which HSCT protocol to seek?" (But there may also be other relevant considerations, such as cost.). There are basically two similar, but different HSCT protocols available that are not identical and deciding which protocol to seek will guide the patient to the specific facility that will administer it. It is important to note that both protocols have so far demonstrated substantially equivalent (very good) curative efficacy based upon the clinical trial population results currently at 10 years post-transplantation. However, there may be other considerations affecting treatment decision which I will explain in more detail.

The first HSCT
protocol is a "myeloablative" chemotherapy protocol that effectively eliminates nearly the entire in-vivo B- and T-cell lymphocyte population of the body. (These are the self-intolerant immune cells that are attacking one's own body that causes MS symptomatic progression and eliminating and replacing them with newly-created naive cells is necessary to stop the autoimmune-mediated destruction of the body's nervous tissue.) Such myeloablative high-dose chemotherapy also results in near-or-complete elimination of the endogenous bone marrow of the body, making hematopoietic stem cell infusion necessary for engraftment and re-growth of the bone marrow (otherwise the patient would surely die without such stem cell autograft rescue). This therapy uses a very effective BEAM chemotherapy administration which is the protocol followed by the US-based HALT-MS clinical trial conducted at the Fred Hutchinson Cancer Research Center in Seattle, Washington (and is also the protocol I received at Heidelberg University Hospital in Germany).

The alternative "non-
myeloablative" (also sometimes called "lymphoablative," although both protocols ablate lymphocytes as the main objective & result of the treatment) protocol HSCT for MS was originally clinically-developed by Prof. Shimon Slavin and Dr. Richard Burt that originated from Prof. Slavin's early observations in a patient with autoimmune diseases that he treated in the early 1980s that resulted in complete cure, together with proof-of-principle in animal models of multiple sclerosis, SLE (lupus) and uveitis (an eye inflammation & blindness disorder that often has an autoimmune component). This novel treatment approach uses a strongly lymphoablative chemical cocktail that is less myelotoxic, destroying a large portion of the in-vivo lymphocytes while sparing a substantial portion of the bone marrow from destruction. This approach allows the damaging autoreactive T-cells to be substantially diminished, while preserving enough bone marrow to allow a shorter duration of time the body must survive with a degraded (but not ablated) immune system. Further, the reason for use of a HSCT autograft is only for the purpose of shortening the timeframe for immune system recovery. The interesting thing about this therapy (as opposed to a myeloablative protocol) is that the patient would likely survive the procedure without a stem cell rescue autograft (although undoubtedly the recovery timeframe would otherwise be longer without it). Administered properly, here is a graph I created that shows the relative engrafted hematopoietic cell population + corresponding innate immune system cellular recovery timeframe for both protocols relative to each other (click to enlarge):


Prof. Slavin & Dr. Burt had originally developed the non-
myeloablative therapy for the main purpose of making a safer and less-risky treatment that maintained optimum curative efficacy. It also appears to have the added benefits of a more prompt recovery timeframe that allows the average patient to more quickly resume a normal lifestyle following treatment together with lesser probabilities of causing early adropause / menopause and intertility. The myeloablative protocol on average appears to require a longer recovery timeframe for most patients together with likely permanent fertility impairment and possible hormone dysfunction, of which is less likely with the non-myeloablative protocol. So I know what you're going to ask. . . . . . . a very valid question. . . . . . "If there is a clearly demonstrated advantage in the safety & recovery profile of the non-myeloablative (lymphoablative) protocol, why would a person ever choose a myeloablative therapy for MS?" The answer is very simple and comes down to a single issue if you think this might be important like I do. . . . . The BEAM myeloablative protocol so effectively wipes out the body's population of B- and T-lymphocytes that the body completely "forgets" the antigen binding sites (epitope) of environmental pathogens & communicable diseases. Following myeloablative chemo conditioning the body loses immune memory accumulated through a lifetime of exposure to infectious agents, environmental antigens and vaccines. Therefore a person needs to be re-vaccinated for all childhood diseases again following myeloablative HSCT. This "loss of immune memory" phenomenon (immune system becoming "antigen naive") is the biggest part of the overall equation as to why HSCT stops the body's damaging autoreactivity to restore immune self-tolerance resulting in a halting of further underlying MS disease activity & progression.

As opposed to the
myeloablative protocol, the non-myeloablative HSCT therapy retains "just enough" immune memory cells that the patient need not be re-vaccinated. . . . Dr. Burt has published his reasoning for why the non-myeloablative protocol does not require re-vaccination as follows:

[For the non-myeloablative HSCT protocol for MS] "Autoreactive memory cells survive and autoantibodies, while significantly diminished, generally remain positive."


Following my own research
comparing the two different HSCT treatment protocols I arrived at my own decision to seek the myeloablative (BEAM) therapy for one specific reason that is just my own thinking that can clearly be characterized as conjecture since I have no proof or evidence that I am correct in my logic here. . . . the surrogate indication of re-vaccination requirement following myeloablative (BEAM) therapy tells me that the immune system is definitively & completely rendered antigen naive and I think has a better possibility of remaining self-tolerant (and MS progression-free) for a longer period of time as opposed to the non-myeloablative protocol that does not render the body's immune system entirely antigen-naive. So far (at 8 years post-transplantation) the clinical results indicate that both approaches have shown substantially similar curative therapeutic benefit. But the question now is "what happens over a longer timeframe, such as 15 or 20 years?" Will the two approaches still have comparable curative efficacy? No one yet knows the answer because we have not yet hit this milestone. But since I was more interested in a durable long-lasting cure as opposed to a more rapid recovery timeframe, I chose the myeloablative (BEAM) protocol in the chance that it "might" have better lifetime curative success. Of course only time will tell on this since there is no way to know the answer today. I may end up eating my own words at some point in the future if my assumption is proven incorrect. On the other hand, if my assumption is proven correct I'm going to be extremely happy that I chose the myeloablative protocol. Eventually we'll see which way this proves out. But if you have MS and are looking to complete an HSCT procedure, you can consider these factors as part of your criteria and decide for yourself. I have created a single page comparison of the most significant aspects of the two treatment protocols. I would have included cost-of-treatment as a line items comparison, but this is entirely independent of the protocol and based solely on treatment facility (click to enlarge):

[The following comments I've added at +2 years post transplantation following my ability to better complete my scientific understanding of the treatment & outcome data of the two different HSCT protocols for MS and is a copy of a message that I recently sent to a friend that had HSCT for his own MS]:


I have only one "potentially" serious concern with the non-myeloablative HSCT protocol. . . . Its a good treatment that has been definitively shown to be effective in the treatment of MS. But because the non-myeloablative HSCT protocol does not completely ablate the entire compliment of in-vivo lymphocytes, "sometimes" (in the neighborhood of 23% of treated MS patients as shown in the MIST phase II trial data) treated patients with RRMS have a MS-relapse following treatment which is then quickly put into remission with additional doses of cyclophosphamide infusions post-HSCT. (This "relapse" phenomenon has not been shown to happen with the myeloablative (BEAM) HSCT protocol that wipes out essentially the entire population of the body's lyphocytes; leaving little or no chance of surviving autoreactive lymphocytes that cause MS disease progression.) A little bit this subject matter troubles me because it seems to indicate that for an isolated few treatment cases the non-myeloablative protocol may be "too gentle" and insufficient to wipe out the necessary fraction of the autoreactive lymphocyte population in these few number of people that results in failure to completely stop the progression of the underlying MS disease activity and allows some forward disease progression (although it is probably at least slowed down). If this happens in an RRMS patient, then it should be easy to identify because the patient will manifest an isolated identifiable relapse episode that should be easy to temporally-spot and treat. However, what happens in isolated progressive (SP or PP) patients in which the MS is not completely stopped by the non-myeloablative therapy? This is a completely unstudied area and creates some concern for me that there could be some progressive patients (PP or SP) that do not have "halted" MS disease activity in using the non-myeloablative HSCT protocol. If such cases do occur then it would seem logical to me that they would also likely benefit from cyclophosphamide re-treatment. But how to identify such "failed" progressive patients? This would seem to be much more difficult to determine because SP and PP MS'ers don't have isolated relapse activity, just further progression and accumulation of MS-induced disability that does not remit. So the question for me is manifold. . . . . how to define an insufficient stopping of progressive disease activity following non-myeloablative HSCT? And if it is determined to be the case, when and how to re-treat with cyclophosphamide to arrest underlying residual disease activity?

I'm just now coming to my own recent conclusion that it might be preferable for progressive (SP and PP) patients to favor a fully myeloablative (BEAM) protocol to avoid the potential possibility of being caught in this grouping of non-myeloablative-treated HSCT patients that experience incomplete disease-stopping and further MS progression. Doing so will likely prevent the possibility of being accidentally caught in such a difficult-to-diagnose / identify situation. But no need to panic reading my words as this is all just pure speculation on my part. I have no direct evidence this is going to be a problem (although logically I think it could be). I still strongly favor non-myeloablative HSCT over any other treatment at all for MS patients with any evolutionary form of the disease. So if it were me with a progressive disease status and I had to choose between a non-myeloablative HSCT procedure (Dr. Burt at NWU in Chicago or Prof. Slain at CTCI in Israel) or no treatment at all, definitely I would absolutely go for the non-myeloablative treatment without hesitation. But on the other hand, as a progressive MS'er (I was) and had the option (I did) of seeking a myeloablative or non-myeloablative HSCT protocol I would choose the myeloablative protocol if available to me (it was and I did).

So here is my current updated thinking based upon my understanding of the differences in "potential" HSCT protocol outcomes. . . . If it were my own respective MS disease status, I would favor the myeloablative (BEAM) HSCT protocol for progressive (SPMS, PPMS) cases. and either of the HSCT protocols for relapsing cases of MS. However, with no other option, I would be totally OK with receiving either protocol HSCT since it would still be a superior-probability option to potentially stop my MS as opposed to all other current pharmacological therapeutic treatment approaches.

The good news about getting
HSCT treatment for MS is that it is not controlled by a single medical facility. It can be had at any number of hospital facilities around the world with widely-varying treatment prices. I only beg you to have it done at a proper & reputable hospital facility experienced in stem cell transplantation. HSCT is a serious & complex procedure. When performed properly it is a relatively safe procedure. But if performed improperly or if post-transplantation monitoring & care is done in a sloppy manner, it can result in severe life-threatening complications. So please make safety your #1 priority (as I did) when deciding where to seek HSCT treatment. A reputable experienced hospital facility should have a well-documented good safety record. Heidelberg (where I went) has a mortality rate in the sub-1% range. Much better than the average of 3% - 5% often (mis)quoted at other average treatment facilities around the world. I'm sure there must be additional facilities elsewhere in the world that I have not listed here, but I am not aware of them. You can do your own research to find an alternate hospital if you desire. Please be wary of inexpensive third-world treatment locations that are offering a price "to good to be true." Don't risk your life gambling on getting a good treatment price for a sophisticated & complex procedure such as HSCT where patient safety should be a priority. A cheap treatment does not make up for the value of your life.

[* Full disclosure * : Except for having received HSCT for myself at Heidelberg University Hospital for my own MS, I have no direct connection or business/financial interest with any of the following listed facilities and have absolutely no competing interest.]



Heidelberg University Hospital, Germany
Professor Anthony Ho

This is a
myeloablative HSCT protocol utilizing BEAM + rATG

Approximate cost (without complications) 55,000 Euros


This is Europe's #1 cancer research & treatment facility. World class and as good as they come from a treatment perspective, Heidelberg performs hundreds of
HSCT procedures every year (for cancer) so they know what they're doing. I won't describe it more because I've already written all about it in this blog.

The only single additional piece of general information I will add something that I recently found out about
. . . . . I had my own HSCT during December so it was cold weather outside so I did not previously become aware of this. . . . . apparently Heidelberg University Hospital does not have air conditioning to cool the patient rooms during summer (although they do have well heated rooms during winter such as when I was there in December). This is a complete shock to me !! I really wonder what kind of modern hospital would not have any air conditioning to keep patients cool in the summertime. I am saddened to learn this because I am otherwise so impressed with the hospital (and especially the staff). So just a suggestion . . . . if you have MS and are going to receive HSCT treatment there, try to plan for a treatment schedule anytime of the year other than summer time, lest you will be cooking in your room. Any other time should be OK. Be forewarned.

Here is a short video of Heidelberg University Hospital:
World-Class Oncology at Heidelberg University Hospital

http://www.youtube.com/watch?v=qF_YfXmd8Lg&feature=player_embedded#!

I will also add some additional important info regarding the criteria that MS patients must meet for acceptance into HSCT treatment. Each and every MS patient must first be approved by the Heidelberg Neurology Department. Although they will consider all data points that make up the puzzle of each patient's specific case, the following list can be considered "general guidelines" that MS patients should meet and show (through documented evidence, primarly through each patient's own medical records) in preparing the treatment application for approval. As a standard procedure all MS patients seeking HSCT in Heidelberg will need to have a neurological exam, consultation and MRI scan as part of the approval process. Basic inclusion criteria as follows:
  • RRMS with previous failure of at least two approved immunomodulator drug therapies.
  • Progressive (SPMS or PPMS) with detectable signs of disease activity (which I assume means MRI lesion activity).
  • Overall, if a patient has clinically-definite MS and continues to worsen despite the use of an approved immunomodulator drug, then acceptance for HSCT is likely (because drug therapy is not being shown to effectively stop disease progression).
  • Must be otherwise healthy & competent to tolerate stem cell transplantation (the transplantation unit also does their own battery of tests prior to HSCT treatment to establish this).
  • These are "basic & general" guidelines as there might be other contributory or mitigating factors associated with an individual patient case that may additionally contribute to the decision process as determined by the Heidelberg Neurology department.
If you would like to seek HSCT treatment in Heidelberg, you can e-mail your inquiry to Sonja Kierschke (Heidelberg University Hospital stem cell transplantation coordinator) at the folowing e-mail address:

sonja.kierschke@med.uni-heidelberg.de

Ottawa General Hospital, Ottawa, Canada
Dr. Mark Freedman

This is a myeloablative HSCT protocol.

Dr. Freedman holds a very special position in the worldwide MS community. He is one of the VERY FEW neurologists anywhere that understands, supports and performs HSCT for MS. I am glad to see him persevere in the face of grossly-unfair criticism from those that ridicule HSCT as a treatment for MS. Clearly such critics have no understanding of the actual underlying (immunological) pathology of MS and of the tremendous demonstrably positive clinical efficacy realized from utilizing HSCT as treatment of MS. As opposed to most neurologists around the world, Dr. Freedman has a clear vision and outstanding scientific-understanding of the well-established benefits of utilizing HSCT for treating those afflicted with Multiple Sclerosis.

Dr. Freedman had previously run
a randomized stem cell transplantation study in Ottawa, but the trial is now closed because they have already completed treatment of all study participants and is no longer available to new patients for treatment.Here is the currently-closed trial he was managing:Autologous Stem Cell Transplant for Multiple Sclerosis (MS/BMT)

http://clinicaltrials.gov/ct2/show/NCT01099930

However, the good news for those MS patients in Canada (only) enrolled in the Canadian health care system, Dr. Freedman continues to treat patients outside of clinical trial & study work. So if you are Canadian, you can get HSCT in your own country if approved for treatment. (Sorry for those MSers outside of Canada as this treatment will not be available to you.)

Dr. Freedman's HSCT protocol utilizes
an interesting (and effective) balance of Busulphan, Cyclophosphamide and rATG in sufficiently large doses to effectively be both myeloablative and strongly lymphoablative.

Here is a well-spoken short video featuring Dr. Freedman. . . .

[Dr. Mark Freedman on] MS and Stem Cells: Time is brain in MS

http://www.youtube.com/watch?v=NhKci3UzSGE

Again, Dr. Freedman's HSCT for MS is only available to those in Canada. Erin McGuey (who's husband Chris underwent this treatment in Ottawa, you can read their blog here:

http://my-end-to-ms.blogspot.com/ 

She also relayed the following helpful information & insight:

"In terms of the clinical trial in Ottawa, it is in fact over. The last patient included in the trial was treated in February 2010. 

 However, other patients, such as Chris, are now being treated outside of the trial. They are being prioritized against patients receiving bone marrow transplants for cancer, which is why we had a two week delay for the transplant.

For Canadians, I have been recommending that they have their neurologists refer them to Dr. Freedman. Dr. Freedman and Dr. Atkins (the hematologist) both examine you and determine if you are a good candidate for the treatment.

. . . . they told me that they have seen their best results in patients that currently have relapse-remitting, but are starting to move towards secondary-progressive.
In the trial, they treated MS patients that had higher EDSS scores, in part because of how [it used to be] high risk the procedure is for a non-life threatening disease.
At this point, I really think they are evaluating each patient on a case-by-case basis.
The good news for Canadians, is that there is NO cost for the transplant, other than relocation for the procedure and for the drugs you use as an outpatient (if you don't have any private insurance). The bad news is that I do not believe they are treating anyone outside of Canada since it is not a trial." [George's comment: Lucky Canadians! How long does it take to get Canadian residency & citizenship? Am I also required to serve in the Canadian armed forces? :-)]

Division of Immunotherapy and Autoimmune Diseases (DIAD) Northwestern University Feinberg School of Medicine, Chicago, USA
Professor Richard Burt


This is a
non-myeloablative HSCT treatment protocol utilizing cyclophosphamide + rATG

Approximate cost (without complications) USD $150,000

Dr. Burt is the first doctor to conduct US-based non-myeloablative HSCT clinical trials for MS, based upon initial work completed by & together-with Prof. Shimon Slavin that currently utilizes some subset combination of
Fludarabine, Cyclophosphamide, Campath-1h and rATG (all strongly lymphoablative agents that does not substantially ablate the bone marrow).

There are few doctors in the world that have more experience utilizing
HSCT for the treatment of autoimmune disorders such as MS. I can't add a lot of additional information specific to his treatment program here because I have not recently spoken with any of the medical staff at Feinberg. The only additional important piece of information that I can provide is that they are currently running a phase III clinical trial that a few MS patients may be able to enter and enable medical insurance to pay for the procedure (but it is EXTREMELY difficult because the inclusion / exclusion criteria will eliminate 99%+ of patients seeking treatment). However, DAID is also treating people as "paid patients" outside of the trial. I have talked to a few other people that paid for the HSCT therapy with Dr. Burt but I do not not know what the specific inclusion / exclusion criteria is. I'm sure it is not the same as (but easier to be accepted) compared to the clinical trial, but likely does favor relapsing patients where inflammatory processes' dominate the disease pathology. If you are progressive you can still inquire with them. Here is the DAID website with contact information:
DIAD (Division of Immunotherapy and Autoimmune Diseases), NWU Chicago, IL

http://www.stemcell-immunotherapy.com/index.html


WHO WE ARE: Richard K. Burt, MD

ttp://www.stemcell-immunotherapy.com/who_burt.html


International Center for Cell Therapy & Cancer Immunotherapy (CTCI) Tel Aviv, Israel
Professor Shimon Slavin

This is a non-myeloablative HSCT treatment protocol utilizing cyclophosphamide + Alemtuzemab
(Campath)

Approximate cost USD $94,000


Prof. Slavin is a world renown doctor with an extensive & distinguished background in cancer and immunological research & treatment having previously worked at both Stanford University and Fred Hutchinson Cancer Research Center together with
Dr. E. Donnall Thomas (winner of the 1990 Nobel prize in medicine for stem cell transplantation). Prof. Slavin is the doctor that originally conceptualized the approach for using a non-myeloablative (he also refers to it as a reduced-intensity conditioning regimen) HSCT protocol for the treatment of hematologically-rooted autoimmune disorders such as MS. Understandably, Prof Slavin's protocol today is quite similar to what Dr. Burt is doing in Chicago (since they have both collaborated in early work) in which Prof. Slavin utilizes Fludarabine, Cyclophosphamide and Campath (all strongly & preferentially lymphoablative agents).

I don't have any first-hand knowledge of the CTCI facility, but I have communicated with several patients that have received treatment with Prof. Slavin utilizing his non-myeloablative HSCT for their MS. They have let me know that the treatment they received from Prof Slavin
was excellent, and they have experienced very good curative efficacy success (both stopping of MS progression and some significant MS symptomatic improvement) resulting from Prof. Slavin's HSCT treatment, although every individual case is likely to be different. I also have had the opportunity to communicate closely with a PPMS patient that completed (September, 2011) Prof. Slavin's non-myeloablative HSCT protocol at CTCI. As of the date of this blog posting it is still too early to gauge the curative benefit he is likely to experience from HSCT, but he reports that his treatment and experience at CTCI was excellent and he feels that he was well cared-for during his stay in Tel Aviv and that he enjoyed interacting with Prof. Slavin. This particular MS patient has let me know that he is happy to share the details of his CTCI HSCT treatment experience with anyone else that is seriously considering HSCT treatment at CTCI. Send me an e-mail and I will connect you with him.

Prof. Slavin on Anti-cancer Modalities at CTCI - Overview: Chapter 1

http://www.youtube.com/watch?v=FzrHS5YgbbE

Prof. Slavin on
Anti-cancer Modalities at CTCI - Overview: Chapter 2

http://www.youtube.com/watch?v=SsBF509OCY8&feature=related


Because Prof. Slavin's non-myeloablative HSCT protocol is so safe and efficacious, I believe CTCI's patient acceptance criteria is the most flexible and open. Likely CTCI would treat any MS patient (RR, SP, PP) that has a postive diagnosis of clinically definite MS. I would bet they would probably reject few (if any) patients seeking treatment, likely wanting to evaluate each patient individually based upon the specifics of each case without regard to inflexible generalized inclusion/exclusion criteria. I believe you would likely find Prof. Slavin very cooperative in evaluating each case for treatment.

CTCI is additionally offering their own proprietary Mesenchymal Stem Cell (MSC) "infusion" therapy for MS that does not include chemotherapy (approximate cost $32K). The procedure is very similar to a phase I clinical trial currently being performed here in the US by researchers at the Cleveland Clinic. Keep in mind that this is very early study work which, by design, is not intended to determine efficacy of the treatment, but is instead intended to evaluate safety & tolerability. So the treated study-population is quite small and I would not expect to see convincing data as to how well this specific procedure works as curative therapy until a number of years from now. However, I am optimistic about this line of work and am really hoping for good clinical efficacy results because the theoretical foundation science is valid for possibly restoring some lost nerve function.

Here's the US-based MSC infusion phase I trial info. (In the title of this phase I Cleveland Clinic study they wrongly use the word "Transplantation." I really wish they had not used this nomenclature because this is not a classic transplantation procedure because it does not utilize chemotherapy and the wording is only likely to confuse some people. It is actually just a (re)infusion procedure. I'm not sure why the FDA let them incorrectly use the term "transplantation." Oh well.):

http://clinicaltrials.gov/ct2/show/NCT00813969

And here is a video report on the subject from Case Western:

http://www.youtube.com/watch?v=-S49VSZheKk&feature=player_embedded

For this therapy at CTCI,
same as the Cleveland Clinic protocol, MSC's are collected from the patient's own bone marrow (probably surgically aspirated from the pelvic bone, but they may also do it by using a mobilization drug (G-CSF) and then perform PBSC collection from the peripheral bloodstream) and then the MSC's are replicated (culture expansion) ex-vivo over a period of 1-3 months to create a substantially large MSC population (in the neighborhood of 1-2 million stem cells per kilogram of body weight) and then re-infused back into the body. (Cleveland Clinic does it all via IV infusion directly into the bloodstream. Slavin does approximately 1/3 via IV infusion and 2/3 via intrathecal injections into the spinal column.)

Clinical paper (for MSC therapy use in MS and ALS):

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036569/

The in-vitro research data with MSC's as treatment for MS looks quite promising. I'm not dismissing it, but because the treatment does not include chemotherapy to ablate self-intolerant immune cells I would not personally do it as a first-attempt treatment because I think it extremely unlikely (or impossible) that it would stop the underlying MS disease process. Although. . . . . . I might seriously think about doing it following HSCT in the possibility that it may effect repair of already-damaged nerve structure & function. However, such an effect has yet to be proved or disproved in human clinical efficacy trials. Here is the small amount of preliminary phase I EDSS clinical outcome data as presented by
Dr. Dimitri Karussis which is not negative, but is also not overwhelmingly positive nor consistent and is why today (without further data) I am somewhat ambivalent about the use of MSC's for MS. (click to enlarge):


However, for everyone else considering such treatment the decision is yours, not mine. I'm just glad CTCI offers actual HSCT that includes chemotherapy that has already been repeatably-proven in population studies to be effective and enable substantial EDSS improvement following transplantation. But if you decide to chance-it and go for the MSC therapy alone without first eliminating the autoreactive immune cells of your body, don't be surprised if there is little, or no positive clinical outcome beyond a placebo effect.

Here is an article & video of a Canadian woman that received MSC infusion therapy at CTCI that appears to have worked well for her specific case. Remember that each case is likely to respond differently
and her case does not directly translate to anyone else. But I have to admit, this is very encouraging and I'm glad to see the work continue and available for those that choose to receive it:

http://www.ctv.ca/CTVNews/Health/20081116/ms_treatment_081116/


The following video presentation by Dr. Dimitri Karussis who works, or worked together with Prof. Slavin describes the science behind the various treatment protocols they provide, including the MSC therapy (which I personally do not favor as first-attempt treatment but would consider it following HSCT once the antigen epitope has been rendered naive via chemo ablation):


CTCI homepage:

http://ctcicenter.com/


Prof. Slavin Bio
:

http://ctcicenter.com/prof-slavin-and-team.htm



Manipal Hospital, Bangalore, India
Dr. Amit Rauthan

This is a myeloablative HSCT treatment protocol utilizing BEAM + ATG

Approximate cost USD $40,000

Dr. Rauthan that oversees the HSCT patient treatment at Manipal Bagalore is experienced in BMT / stem cell transplantation from prior experience working in a hospital in Atlanta, Georgia, USA. In addition, Manipal Bangalore stem cell transplantation department has some form of cooperative relationship with the University of Minnesota. Since Dr. Rathan is a classically-trained hematologist / oncologist he knows, understands and is experienced in how to properly administer BEAM protocol autologous HSCT.

Manipal has modern medical equipment and follows internationally-accepted medical protocols. (I especially liked the good sign that they utilize positive-pressure HEPA-filtration patient recovery rooms following HSCT. Very appropriate and nice.)

Additionally, I think it important to highlight the fact that Manipal fills a currently-unmet need in the MS community in which the attractive pricing of the procedure at Manipal ($40K) will likely open and make available the HSCT procedure to many MS’ers that are otherwise unable to afford the treatment at other suitable facilities (all of which have a higher treatment price point for the same/similar treatment regimen). I’m glad to know that this (large?) niche market can be served by Manipal for those that choose this treatment route.

I have not personally (yet) met Dr. Rauthan (but have exchanged messages and video Skype with him), and have also not been to India myself (although I’m sure I’ll visit there someday). The credit for finding Manipal and Dr. Rathan to perform HSCT for an MS patient goes entirely to Richard Syrop, here in the Unted States. Richard’s wonderful wife, Bunti, was diagnosed with PPMS with a continuously-worsening disability status over time.

Based upon Richard's excellent understanding of the curative probabilities of HSCT for MS, Richard and Bunti decided to go with the (good) likleyhood that her underlying MS disease might be stopped via HSCT. As of today, Bunti has indeed experienced a halting of her underlying MS disease activity and progression, as well as some marginal, but definite and meanigful improvement of her ambulation status (actually a good result for a PPMS case).

Richard and I had a chance to frequently communicate before, during and after Bunti’s HSCT procedure at Manipal. I’m not a doctor, but from having gone through myeloablative (BEAM) HSCT for my own MS and having researched the medical treatment aspects rather thoroughly, it sounded to me that Dr. Rauthan did a superb job of managing Bunti’s (and so far two additional subsequent patients) treatment regimen and recovery. I haven't yet heard of a single medical misstep by Dr. Rathan relative to his administration of HSCT and corresponding patient care and experience. Although HSCT is normally a tough procedure for anyone to go through, Bunti and (so far) several other MS patients have completed the procedure without any life-threatening complications and are all now recovering normally, and well following the completion of their transplantation procedures. (My hat's off to Dr. Rauthan!) I’m looking forward to the day some number of months later when all these patients will likely definitively report their MS disease as halted, and hopefully reversed, as well, which is a realistic expectation. They have my sincerest best wishes, especially following the decision to tackle MS head on. Kudos to all of you! In addition to these patients already-transplanted, I am aware of more MS patients scheduled for pending transplantation with Dr. Rauthan at Manipal. Aside from the geography of India, I now personally have enough confidence in Manipal that I would seriously consider treatment here if I were currently seeking HSCT for myself.

Here is some basic information regarding Manipal and Dr. Rauthan:

Manipal Hospital, Bangalore


Dr. Amit Rauthan (BMT-experienced in the United States)


University of Minnesota BMT program opens in Bangalore, India


Manipal has set up a formal acceptance procedure for MS patients seeking HSCT. They have additionally formed a patient review committee (a common practice at many hospitals) to review applicant cases for treatment approval. HSCT being such a serious and complex procedure they want to make sure that the treated-patient is not going to be put at excessive risk while simultaneously attempting to maximize the curative benefit of the treatment. You can send a treatment request to the following Manipal e-mail address (I’m sure at some point they will ask for some personal medical info and/or medical records that you should gather together) and then they will make an acceptance decision within 2-3 weeks timeframe following review. Please specifically reference that you are interested in BEAM HSCT for treatment of your MS with Dr. Amit Rauthan in Bangalore:

mipc@manipalhospitals.com

The following is a great video of Australian Min Beattie's treatment result at Manipal for her own MS. . . .

http://aca.ninemsn.com.au/article.aspx?id=8605305

You can also check out the following blogs/sites of several people that have completed, or are currently in HSCT-for-MS at Manipal:

Geoeffry DB (USA)

https://www.facebook.com/groups/113034538879355/


I just wanted to add a last note about India. . . . In a previous posting I mentioned that the Apollo Hospital network in India would also be willing to perform HSCT for those with MS. And when I contacted them in August of 2009 they did agree to do HSCT for an MS case like me, sight unseen. However, since that time the CCSVI scam craze has gotten so big and out-of-control that now Apollo appears to be refusing to to do HSCT for MS because they claim they consider it "experimental" (when in actuality it is far from experimental since it is now in final FDA phase III clinical trial), and instead are now pushing MS patients to get CCSVI treatment. Since CCSVI is not only 100% experimental with absolutely no evidence at all (none, zero, zip, nada) that there is ANY proven beneficial effect whatsoever from CCSVI treatment for MS (there is no valid clinical study data to even remotely suggest that it has any beneficial effect on MS beyond a temporary placebo effect), I am sorely dissappointed that Apollo has decided to take this hypocritical & unethical approach putting money squarely ahead of patient's health. I have now lost all respect for the Apollo hospital network in India and would never even suggest to anyone to consider treatment there. Very sad.


The A.A. Maximov Department of Hematology and Cellular Therapy, National Pirogov Medical Surgical Center, Moscow, Russia
Dr. Denis Fedorenko

This is a non-myeloablative HSCT treatment protocol utilizing Cyclophosphamide + Rituxamab or alternatively Cyclophosphamide + Carmustine

Approximate cost USD $40,000

I have spoken with Dr. Fedorenko at Maximov in Moscow on the phone to discuss his HSCT-for-MS treatment. He is a very nice and pleasant person that clearly is a very knowledgeable medical scientist and clinician and I found him to be open & helpful with my questions. Maximov/Perigov is a well-respected hospital facility. And the best news is that Dr. Fedorenko is definitely extremely knowledgeable and he clearly understands well all the fundamental medical science behind HSCT for treatment and cure of a wide range of hematologically-rooted autoimmune disorders. (Perhaps he can be thought of as providing a similar treatment service in Russia as Dr. Burt does in the USA.) Dr. Fedorenko is also well-published on the subject of HSCT treatment of autoimmune disorders, being involved with numerous and ongoing scientific and medical international symposiums and publications, a few such as listed here (there are many more than just these):

http://www.stemcellms.ru/doklad11.php

https://ash.confex.com/ash/2010/webprogram/Paper26601.html
http://onlinelibrary.wiley.com/doi/10.1002/emmm.201100129/full

Based upon his publications and experience, Dr. Fedorenko has the credentials establishing him as an expert in the field of HSCT treatment for autoimmune disorders.

Here is the Maximov website:

http://www.gemclinic.ru/english.php

And a web page with a little more info and a few pictures from the facility:

http://translate.google.com/translate?sl=ru&tl=en&js=n&prev=_t&hl=en&ie=UTF-8&layout=2&eotf=1&u=http%3A%2F%2Fwww.pirogov-center.ru%2Fclinic%2F5%2F&act=url

There are two English-only speaking patients that recently travelled to Moscow and received HSCT treatment for their MS from Dr. Fedorenko at Maximov. I have communicated extensively with both and they both have reported very good treatment experiences despite their inability to Speak Russian. They are Phoebe Scopes from London, UK and Amy Peterson from Texas, USA. (Coincidentally, their treatment schedules overlapped in Moscow.) They both have created very informative blogs you can read to learn about their treatment experience with Dr. Fedorenko. And based upon their reported experiences I have come to have a very high confidence level in both Dr. Fedorenko and the Maximov hospital facility. I would have no problem going here for treatment myself.

Here is Phoebe Scopes' HSCT-for-MS-at-Maximov blog. . . . . . .

http://hsctmsandme.weebly.com/about-me.html

And Phoebe providing more detail about the Maximov facility. . . . . . . .

http://hsctmsandme.weebly.com/aa-maximov-hospital.html

And Amy Peterson's HSCT-for-MS-at-Maximov blog. . . . . . .
 
http://amygoesninja.wordpress.com/

And here is a local news segment about Brook Slick making the trip to Moscow for the transplantation. . .

http://wearecentralpa.com/fulltext/?nxd_id=454552&fb_action_ids=4128434708108&fb_action_types=og.likes&fb_source=aggregation&fb_aggregation_id=288381481237582

Treatment inquiries should be sent to the following e-mail address where Dr. Fedorenko will receive it:

info@gemclinic.ru

Dr. Fedorenko may also be contacted in Moscow at the following telephone number:

+7-915-290-00-67   

Based on my discussion with Dr. fedorenko, here is relevant info I have learned about Maximov's HSCT treatment for MS:

Maximov performs HSCT for both bone marrow malignancies (such as leukemia) and also several types of autoimmune diseases.

For cancerous conditions they perform a fully myeloablative HSCT protocol utilizing BEAM (very common around the world).

For autoimmune disorders they perform a non-myeloablative HSCT protocol utilizing primarily a combination of carmustine + cyclophosphamide. I never previously heard of this specific chemical combination being used, but it makes sense to me and seems like a reasonable treatment application. I don't see any red flags.

Maximov has ten treatment beds for treating a maximum of ten patients at one time. Five beds reserved for cancer patients, and five beds for patients with autoimmune disorders.

HSCT treatment criteria for autoimmune (MS) conditions:

- Exclude patients greater than 50 years of age

- Must be in sufficiently good health to tolerate HSCT procedure) includes good heart and renal function and generally be in good overall health),

And specifically for Multiple Sclerosis patients:

- Must not be 'severely' disabled (patient must be ambulatory with an EDSS of less than approximately 6.0)

- Will treat any evolutionary form of MS (RRMS, SPMS and PPMS); all allowed but must demonstrate active MRI lesion activity or alternatively if without active lesions must have experienced greater than a 1.0 worsening of EDSS over a period of one year.

For MS specifically this seems to me to be rational and justifiable treatment criterion.

- Maximov previously treated more than approximately 200 patients (mostly Russians) with autoimmune disorders in which a very small number (3-5) developed "serious" treatment complications (such as sepsis), of which everyone recovered. There have been no deaths or Treatment Related Mortality (0% TRM).

- Treatment appointment should be scheduled at least one month in advance.

- Maximum pre-treatment exam duration = 1 week.

- Hematopoietic stem cell PBSC mobilization (with G-CSF) = 4-5 days (2-4M HSC's / kg body weight collected).

- Peripheral blood stem cell collection / apheresis = 1-2 days.

- "Usual" total in-patient hospital stay (inclusive of all procedures) = 30-45 days.

- Approximate price = $40,000, inclusive of all items listed above.

- Language: Russian is (of course) the primary language. Non-Russian-speaking patients OK (doctors all speak English), however the nursing staff is unlikely to be proficient in English. But since all the doctors do speak some level of English and are present on a daily basis they can assist with patient interaction. Based upon their direct experience, both Phoebe and Amy have reported that the language barrier was not a huge hurdle and they all (together with heir husbands with them) were able to interact adequately as English-only speaking patients.

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I am also working to validate/verify the potential for three additional HSCT-for-MS treatment facilities. All three of which have previously treated MS patients, but I have not yet discussed the topic with them directly and am reluctant to "officially" list them on this page until I do so. So if you would like to consider treatment at any of the following three facilities, please don't rely on "my" endorsement until I have a chance to more thoroughly vett them, which I will try to do as soon as I have time. But you are welcome to pursue treatment at the following on your own if you desire. . . 

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University of Cape Town (UCT) Hospital, Cape Town, South Africa
Prof. Nicolas Novitsky 
Myeloablative (Busulphan) protocol
Approximate cost USD$55,000

Here is Prof. Novitsky's criteria as I currently understand it and I will verify as I have time:

  • Confirmed positive diagnosis of MS
  • Relapsing–remitting, secondary progressive, progressive–relapsing forms of MS 
  • Age between 18 and 55 years 
  • Disease duration [more than] 1 year 
  • Expanded Disability Status Scale (EDSS) between 3.0 and 6.5 
  • Clinical or MRI activity in the previous year
UCT website:

http://www.ucthospital.co.za/

Prof. Novitsky information:

http://www.haematology.uct.ac.za/staff.htm

http://www.medpages.co.za/sf/index.php?page=person&personcode=25331


The following is the blog of the very nice South African Bernard Cronjé that had HSCT performed there for his own MS in the latter half of 2012 in which he describes his good treatment experience:

http://bjcronje.wordpress.com/

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Akademiska sjukhuset, Uppsala, Sweden
My understanding is that Uppsala previously performed a myeloablative (BEAM+ATG)  protocol, but have now tied together with Dr. Burt's Chicago MIST trial and now offer trial participants the non-myeloablative protocol (cyclophosphamide + rATG) as used in Chicago.

The Facebook page of the wonderful Swede Chrisopher Martinsson that can only be described as a fantastic success story in which he received Uppsala's myeloablative HSCT:

https://www.facebook.com/notes/christopher-martinsson/a-new-beginning/328987160453332

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Karolinska University Hospital, Stockholm, Sweden
Prof. Hans Hãgglund
Myeloablative BEAM+ATG  protocol
Approximate cost USD$110,000

The following two blogs by wonderful Norwegian women that both had HSCT performed here for their own MS:

Hannah Vesterager (Norway)

http://www.hannastamceller.blogg.no/

Elin Maageng Jakobsen (Norway) 

http://www.mindevenmore.com/


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As I mentioned previously. . . just because I am not aware of other facilities, that does not mean that there are not other hospitals that would be willing to perform HSCT for MS patients. Please feel free to look around for other (good & safe) treatment facilities if you are so inclined. You may want to use the following EBMT link to help in your search as I did (which is how I found Heidelberg University Hospital):

http://www.ebmt.org/Contents/Pages/Default.aspx

If I can help anyone with understanding more about treatment issues & options, feel free to send me an e-mail. I'll try to respond as soon as I can:

georgegoss@yahoo.com