Saturday, November 28, 2009

Preparing for the treatment in Germany

First and foremost. . . . Having MS is NOT a death sentence. Some people have a relatively benign and modest form of the disease. And some people have a severe form that is very debilitating. But one thing about MS. . . it very rarely causes a decrease of lifespan. MS is really all about impact to lifestyle.

I've been pretty lucky up until now. I didn't get it nearly as bad as other people, But it IS getting worse. And that puts the fear into me that I will have trouble supporting my wife and son. If they were not in my life I wouldn't even consider such a risky and awful procedure like a stem cell transplant. But because they are the most important part of my life, I have to take the risk to cure my MS so I can be part of the life of my treasured family. I don't want miss out on this wonderful experience with my wife (Yuko) and son (Riki) if there's anything I can do to about it. And I can. . . . get an ablative stem cell transplant.

So the first thing I've had to prepare is my state of mind. All I have to do while here alone (at first) in Germany is look at the pictures of Yuko and Riki and then there's no stopping me. . . full steam ahead to seek the cure for MS. I figure that I'd jump in front of a speeding bus to save them. So why not do something less radical. like a stem cell transplant? Easy logic, easy decision for me.

Riki at daycare on Haloween 2009. Melts my heart.

OK, now that the most important decision is out of the way, what did I do to prepare to get here? The first thing is education. I learned everythinbg I possibly could about the treatment regimen and the treatment outcomes for MS. As for the regimen, the most abundant info comes from cancer treatment resources. Read everything I could. This way I can converse with medical staff in approaching and conducting the treatment to a succesful outcome.

For treatment outcomes with MS, this is still earlier in the information lifecycle, as opposed to later. There is not as much data for this BMT treatment on MS as there is with other diseases such as cancer. There have been 6-10 initial small studies for doing BMT for autoimmune diseases such as MS, and all of the study data is very consistent. Although there is demonstrated benefit for all forms of MS, it works better on earlier forms of MS with less total present disability (EDSS scale less than 6.0).

Preping for the return I expected that I might still have some eating or digestive or (low) weight issue, so I purchased several cases of ensure-like nutritional drink and put it in the refrgerator for when I return. I think I will be thanking myself for doing this. And just for the heck of it, I also bought several boxes of high-protien nutrition bars to go along with the nutrition drink. Just to be on the safe side.

As for an MS-specific issue. . . . the studies to date indicate that most MS patients have a transitory worsening of existing physical deficit with BMT treatment. Since my legs are weak, I expect the treatment to possibly cause a temporary problem with walking directly following the procedure. For this reason I bought a portable, lightweight wheelchair that can go on an airplane. I bought this one. . .

This is an expensive chair. But man! I gotta tell you I love this chair. Made by a Japanese company this is a engineering work of art. It's super lightweight, folds up very small and can be used to wheel someone on an airplane (which likely will be my case). Basically it is made extremely well. The best materials and best engineering practices to construct it. And no, I don't own any stock in this company nor do I get a sales commission. I'm just an engineering geek and this chair is a geek's dream. The only thing is that someone else has to push the chair. It is not the self-locomotive type. If you want it, I'll sell you mine after I return because I'm confident I won't need it for a long time. I'm planning on being cured!

I think this one is important and makes me feel especially appreciative of my wife. . . . she bought an electronic picture frame and loaded pictures of us together along with Riki. When I plug it in it cycles through more than 100 great family images. At the time I'm alone in the hospital I can watch this. I think it will help me tremendously.

OK, last thing. Of couse I'm going to lose all my body hair. So before leaving I had my head shaved.

But it turns out that my chemo-induced hair loss likey will not occur for several more weeks. So I probably jumped-the-gun a little on this. My hair is already growing back rather quickly. I'm going to have to repeat this head-shaving ritual again in a couple weeks so that I don't have to watch it come out on the pillow. [Post-transplantation note: The optimum day to shave your head is day +1, after all the chemo is administered and just before the hair all starts coming out on its own. The hospital facility should be able to do this (head shaving) in the hospital room for you. Don't just let it fall out on its own. Its ugly and messy.]

As for Germany, just two things. . . . make sure all electronics operate on 220V, 50Hz, and have a travel plug adaptor for Germany-specific outlets. If you're from North America or Japan, the one like this will work fine:

There are no US outlets anywhere here. That goes along with the lack of Japanese-speaking individuals.

That's all. See you tomorrow!

What I'm expecting during the treatment

Greetings to my friends and interested visitors,

Preparing for the trip & treatment has taken a considerable amount of my time. Probably more than it should have because I've had no one to walk me through what exactly I should expect. I found it extremely useful to read information from cancer treatment resources (since the treatment protocol is almost the same), but have also had to consider how my own MS-infected body will respond to the therapy as well as consider the logistics of seeking treatment in an overseas adventure. I will comment in my next post regarding what I've done to prepare for the trip & treatment. For now, most of the following info will be of biggest benefit to those with MS that might seek this treatment.

It is important to understand that the general schedule and details of the treatment regimen that I outline here are just estimates based upon my general understanding of the process. I won't find out for certain what my exact schedule will be until I check-in at the hospital with my physician (Dr. Raab). However, the BEAM protocol I will be receiving is roughly divided into two parts, as follows:

1) Mobilization & collection - this phase is usually done in an outpatient setting, usually taking 5-8 days. In earlier days of collecting the hematopoietic stem cells, a surgical procedure using general anesthesia was performed in which bone marrow is aspirated from the pelvic bone. This procedure is not now commonly used (but sometimes still is), but has been predominantly replaced by a non-surgical procedure. First a chemical growth factor (called Granulocyte Colony Stimulating Factor, G-CSF) with Amgen brand name Neupogen is administered. G-CSF causes the stem cells in the bone marrow to replicate, over-populate and then diffuse into the peripheral blood stream. After some days of this treatment (usually five days of Neupogen injections) there is an overabundance of stem cells in the peripheral bloodstream that are ready to be harvested. A venous catheter is then inserted (sometimes in the jugular vein) that allows the extraction and return of blood, similar to a dialysis process. The blood is put through a process of apheresis using a centrifuge and filter membrane to extract the stem cells and return the other blood constituents to the body. The stem cells are then promptly cryopreserved at liquid nitrogen temperatures to be thawed later during re-infusion.

2. Ablation (conditioning regimen), Infusion & engraftment - A short time following stem cell collection, I will be admitted to the hospital to begin receiving the four chemicals (BEAM) of high dose chemotherapy. It's interesting to note that a couple of the BEAM drugs are derived from the same chemical agents originally developed in World War 1 as mustard gas weapons. So needless to say, these are very nasty and very strong drugs. The BEAM chemicals will be delivered over a period of 4-6 days, with the end result of a completely ablated (killed) immune system, bone marrow and associated hematopoietic stem cells. At this point, death would be a certainty without getting my preserved stem cells back to regrow my blood cells-producing bone marrow. I have to imagine some people in treatment wondering if their stem cells were properly frozen and hope they weren't accidentally misplaced or lost. However, I trust that the hospital will treat the preserved stem cells the same way the Smithsonian treats the Hope diamond. Very carefully. Still funny for me to imagine that my life will be located in some plastic bag that is out of my sight.

A day, or two after the final BEAM chemo administration (when the chemicals dissipate from the body), something magical happens. I get my life back! Cancer patients getting a Bone Marrow Transplant (BMT) often refer to this day as their "Birthday." It's the re infusion day, taking less than half an hour to just do an IV drip of my own stem cells back into my body after they are thawed out in a sink of warm water near the hospital bed. In technical terms this is called "Day 0," or just zero day. All days of treatment prior to this day are numbered -1, -2, -3, etc. And of course all days following are numbered as +1, +2, +3, etc. Once the stems cells are back into my bloodstream, they naturally migrate into the bones and (hopefully) begin to grow and multiply where the previous bone marrow existed. This re-growth process is called engraftment and takes anywhere from +8 to +20 days to show initial signs that it is occurring by measure of white blood cell count increase. During this time I will be at risk for complications that are divided into two categories:

Life threatening

1. Infection
2. Infection
3. Infection
4. Cytopenia (lack of red blood cells or platelets, both of which require blood transfusions and is commonly required for many patients sometime after day 0)
5. Venous Occlusive Disease (VOD), now called Sinusoidal Obstructive Disorder (SOD) where the small veins in the liver collapse (from the chemo) which sometimes results in fatalities. Unfortunately there is no practical treatment for this condition so hopefully it will just not occur.

Obviously infection is the #1 concern and is responsible for approximately 80% of the fatalities inherent in this treatment procedure. So suppressing possible opportunistic infections is critically important and is why I will be treated prophylactically with antibiotic, anti-viral and anti-fungal medications. All it takes is one small opportunistic infection to flare up and cause a bad day in the worst possible way.

Non-life threatening

1. Nausea. Pretty much a foregone conclusion. Treated with steroids.
2. Mucositis (canker sores that can manifest anywhere throughout the mouth and GI tract). 80% of BEAM people get this affliction preventing eating and drinking for about a week starting sometime after day 0. People sometimes report difficult and painful breathing. Although not fatal and only temporary, frankly this is the issue that scares me most.
3. Hair loss. No duh! But it's ALL the hair on the body. Including eyelashes. Personally this doesn't bother me like it might bother other people. I think it will be interesting. I shaved my head before going over to Germany. It's better than having it come out in clumps on the bed pillow.
4. OK, I'm not going to list the rest. There are many. You can read about them here:

As far as complications go, it seems to me the best defense is having a medical team that is both experienced, and conscientious (i.e. careful). With the BMT team at Heidelberg University they do over 300 of these procedures every year. That is quite a few (among the top transplant centers by volume), and they obviously have the experience. To top it off, Dr. Marc-Steffen Raab will be my attending physician responsible for my overall treatment. He is not only extremely experienced with many international collaborations (including Dana Farber Cancer Institute), but also Dr. Raab currently manages a number of patients in the Autologous Stem Cell Transplant unit at the hospital. And although I have yet to meet the other clinical staff that will be responsible for my care, I think that I will likely be satisfied with the professionalism and capability of the hospital and BMT unit staff. I'll let you know.

Of special mention regarding the Heidelberg staff. . . for my first interface and learning about Heidelberg's capability (and willingness!) to perform the BEAM protocol for treatment of my MS, I worked with Dr. Markus Thalheimer to learn about the opportunity and details of having the treatment in Heidelberg. Dr. Thalheimer was exceptionally helpful, courteous and very professional. And most of all, he did an exquisite job of allaying my fears about the procedure by explaining everything to me in satisfactory detail. ("In technical terms, its not really a 'transplant' since we're using your own stem cells. It's mainly just a chemotherapy procedure.") In actuality he is totally correct (so long as my stem cell bag isn't lost with the Christmas mail! :-) ).

And the other good thing for me is that I don't have cancer. Having cancer can create serious comorbidity issues that lessen the sucess rate of BEAM therapy. I have to think that because I am in otherwise good physical condition, chances of a successful outcome are improved.

I "expect" the procedure to follow not far from my expectations, and hopefully to be discharged (barring complications) early January. I hope to return to California perhaps around January 8, contingent upon the "actual" schedule Dr. Rabb will provide to me when I check in on Dec 3.

Next post about what I've done to prepare for the travel & procedure.

Thanks to everyone!

- George

Tuesday, November 24, 2009

Introduction to the voyage

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

Greetings, I have created this blog both to update my family & friends on the status of my journey through this trying process, and also to share with all others about the exciting prospect of a cure (really!) for Multiple Sclerosis. I will start this blog with some background, then a technical description of what I am doing, followed by a step-by-step description of the journey of treatment as I progress through it. I plan to follow-up after the treatment and report on the Treatment result and efficacy, either way it turns out (but I expect that I will eventually be "cured" of MS). I will periodically include some video posts to simplify and clarify the information that I will plan to share.

Make no mistake about it. . . . I fully expect that in a matter of ten years, or less, this treatment regimen will become the standard treatment to cure MS. I consider myself among one of several hundred people so far to be pioneer patients to prove this therapy works.

A little about myself. . . . I am 45 years old and was diagnosed with clinically-definite MS when I was 31 (the average age of MS diagnosis at 30 years for the total population). The presenting symptom at the time of my diagnosis was optic-neuritis (as is the case with approximately 60% of all people first diagnosed with MS). Up until a few years ago I followed a course of relapsing-remitting (RR) type of MS, but am now essentially secondary-progressive (SP). So to explain the overall idea and plan of what I am doing, here is a letter I wrote to my good friend that explains what's going on. . . .

Hi Yokota-san, I wanted to update you on my plans that we have discussed regarding my seeking a cure for my Multiple Sclerosis of which I was diagnosed in 1996. It turns out that contrary to classical beliefs, there is a "probable" cure for Multiple Sclerosis. In this case probable means 80% chance of positive outcome and cure means a "halting" of progression (not total reversal, although there may be a 30% reversal of existing physical deficit). Another good point is that all the research to date indicates that it works on all forms of MS.

I entered a secondary progressive phase a few years ago and continue to have a slow progression of continual deficit, which is quite common for the long-term course of the disease. So although I no longer have specific relapses (flare-ups), I continue to slowly degrade. It is already becoming rather fatiguing to walk several hundred meters. So although I still function relatively well, I can guess where my status will be in ten years if the course of my MS disease is not altered.

The cure? It's an autologous hematopoietic stem cell transplant (historically referred to as a bone marrow transplant, although that term is not commonly used now). I will spare you the technical details for now, but suffice it to say that it turns out to be an amazingly statistically effective treatment. So much so that I am going to undergo the procedure this coming December. And as a result I fully expect to be cured of any further MS disease progression. [Post transplant note: End result: It worked!] And on top of that I can discontinue my current interferon injections which is standard therapy for many people with MS. Yippee! No more chronic injections after that.

I honestly believe that in the future this treatment protocol will become the standard treatment as a cure for MS. Interesting that the reason that it currently is not is because it is still in phase II [now phase III as of 2011] clinical trials around the world. [Post transplant note: All the phase II trial patients have been treated with all having demonstrated successful curative results and are being monitored during long-term follow up. The procedure is currently into phase III randomized trial starting in 2010.] Also because it is a very aggressive medical treatment there is some mortality associated with it (perhaps somewhere around 5%. . . . I figure a 1 in 20 chance of death is not as good as a Space Shuttle ride, but it’s a hell of a lot better than a game of Russian Roulette with a revolver!). [Note added post-treatment: The mortality rate with this treatment at Heidelberg University Hospital is actually closer to a low 1% for an otherwise healthy individual. Not nearly as scary as I originally thought.] In addition, the treatment has a high probability to cause irreversible sterility due to the strong chemo. As far as other common side effects go, I also get to temporarily lose all my hair. (Not such a bad thing. It's practically all gray anyway. I wonder if it will come back brown again?) However, the main thing is that this procedure is also sure to be a damn uncomfortable procedure, just as the same procedure is often used to treat many forms of cancer such as leukemia, multiple myeloma and Hodgkin's & non-Hodgkin's lymphoma. Something like a living hell for a few weeks [Post-transplant note: OK. . . it's definitely uncomfortable. But it's not actually a "hell" experience.] while getting the high dose chemo and being in a clean environment while the stem cells repopulate and reactivate the immune system. This procedure is like hitting the "reset" button on the body's immune system. Taking it to zero and then bringing it back up to life again. [As a curative treatment HSCT works by erasing the body's immune system memory, changing the body's overall T-cell epitope (antigen binding) repretoire, inactivating autoimmunity (making the immune system "antigen naive") restoring immune self tolerance. This is often referred to as "resetting" the immune system which stops the underlying disease activity and progression of MS. Once achieved, the body then has a chance to repair (or compensate for) some of the existing neural damage that is not undermined by further MS disease progression.] In fact, even childhood and lifetime immunity goes away following the procedure. It becomes necessary to be re-vaccinated against childhood diseases such as tetanus, polio, measles, etc because my body will no longer recognizes them as foreign invaders. Presumably the same reason that my body stops attacking itself as is the case in an autoimmune disorder like MS. Problem for me (and anyone else seeking the treatment) is that within the United States [& Canada] it is currently impossible to receive this treatment for MS outside of a clinical trial. [Post transplant note: This is no longer true. See this web page: ] I tried to enter a trial in which I thought I was an ideal candidate in the following program:

But alas I was rejected from this trial for some technicality of documentation or paperwork, or something like that. I searched in vain for a US facility that would perform the procedure for me, but there are absolutely none in the US [or Canada] that will do it for MS outside of a clinical trial because US facilities are overly-paranoid of lawsuits, which is a shame because it is a treatment with excellent clinical outcomes. And even if I did find one in the US that would be willing to perform the procedure, the price tag is around $200K. Outside of the budget I had in mind and not a single penny covered by insurance because it is still considered "experimental" (even though the overwhelming data suggests otherwise).

So I started looking overseas for a facility that would agree to perform this treatment. The usual suspects were first on my list. . . India, China, Brazil and others. These locations will perform bone marrow transplants cheaply, and no questions asked. And indeed these places may even do a terrifically good job for this type of procedure. But frankly, I personally don’t know enough about these locations to know if they would be good treatment options. I just don't want to experiment with my life to find out with a possibly risky procedure like this. So with further investigation on the international bone marrow donor [EBMT] site I started checking out facilities in Europe. I figure the Germans are a good bet because of both the scientific excellence, and also because they have medical regulations that are on-par with the FDA here in the US.

I quickly learned about Heidelberg University Medical Center where they perform over 300 transplants a year. I contacted them and found out that they have even previously done some transplants for MS. They seem to me to be an exceptionally capable and experienced organization. So I've decided to go with Heidelberg this coming December. I'll have to be in the hospital a little less than a month. Then an outpatient checkup ten days after discharge and then I can return to California and be cared for by my own Kaiser doctors for the monitoring period lasting several more months, to a year.

And the great news. . . total cost in Germany is about 50,000 Euros, plus travel and housing costs. That comes out to approximately [less than] half of what it would cost in the US. Much more affordable. And for me, personally, a reasonable price tag to cure my MS. Of course with having the option, it's difficult to imagine anyone "choosing" to go through this treatment living hell if they didn't have to. (Most cancer patients have only the alternative option of death, so it’s a no-brainer decision for people in that situation. With MS patients, death is not the option. Just further potential disability.) But I'm going to do it for my wife and my son. I don't want to miss out on participating in the future growth of my son's physical activities. Or at least I don't want to be completely excluded from them. I think this procedure will enable me to accomplish this goal.

So just a final note. . . . I believe that I very well may be one of the first, if not THE first person in the United States to seek this treatment outside of a clinical trial. (My hat’s off to the Germans for recognizing the importance of helping people with treatment, as opposed to just doing research for the sake of research!) So to share the experience and the details of the process and outcome with friends and interested parties, I am doing a blog about the whole experience. I just set up the site so it may take a few days to start posting the info & videos. Here’s the blog site:

I’m looking forward to seeing you upon my return from Germany, Yokota-san. You are a true friend!

Best regards,


So there you have the summary of what this is all about. There are currently two similar, but different forms of curative treatment regimes of the bone marrow transplant type undergoing phase II clinical trials. The goal is the same for both treatments (a halting or reversal of disease progression). However, these two treatment protocols differ in one substantial manner.

The treatment that I will be receiving in Germany follows the HALT-MS study protocol under the direction of Dr. Richard Nash at the Fred Hutchinson Cancer Research Center which is a fully ablative regimen. That is, the bone marrow is completely destroyed by high-dose chemotherapy (myeloablative) prior to the re-infusion of my own stem cells used to reconstitute the immune system that will have been collected prior to the high dose chemo.

The other program, called the MIST trial pioneered by Dr. Richard Burt at Northwestern University recognizes that the fully myeloablative therapy is risky with approximately a 5% mortality. [Post transplant note: BEAM myeloablative treatment at Heidelberg University Hospital is actually closer to a low 1% mortality rate.] So Dr. Burt developed a regimen that is not so aggressively myelotoxic, but is instead predominantly & aggressively lymphoablative which does not kill off 100% of the bone marrow, reducing the period of time a patient must survive with degraded (not ablated) immune function. This results in reduced risk of treatment complications (infections) with an associated mortality rate of well under 1%. All of the initial indications are that this non-myeloablative protocol has good clinical benefit at several years out, albeit it is still not established for how long this benefit will ultimately last. (Is it lifetime, or is it temporary? Only time and the ongoing population study will provide the answer.)

A graphical comparison of the immune function recovery for the two protocols (click to enlarge):

The unfortunate part of the MIST study is that this therapy is difficult to find outside of a study trial [Post transplant note: Please see the following page for a list of facilities that will provide HSCT today: ] because it makes use of a very unique chemotherapy protocol not used for cancer treatment consisting of either (Fludarabine + either Cyclophosphamide or Campath-1h) or (Cyclophosphamide + rATG) that rapidly ablates in-vivo lymphocytes while only mildly (and incompletely) ablating the hematopoietic stem cells in the bone marrow. I contacted Dr. Yvonne Loh at Singapore General Hospital (she previously worked with Dr. Burt's team with MIST) to inquire about treatment availability in SGH's BMT unit where they use a Flu/Cy (Fludarabine + Cyclophosphamide) protocol. Singapore law does not disallow the treatment to be given to patients outside of a trial, but unfortunately Dr. Loh has been unable to make the transition from researcher to clinician and applies the overly-restrictive (and in my opinion, clinically ridiculous) inclusion and exclusion criteria from the MIST trial that eliminates 99%+ of people that might want this treatment. So even if one wanted this alternate therapy, it is virtually unavailable. It's too bad that Dr. Loh lost sight of helping people in a clinical environment as she is still blinded by the quest for proving a hypothesis in the context of a study program.
Regardless, for me the main determinant for which therapy I prefer revolves around a simple concept that I believe is based upon solid science. Following the MIST protocol, treated individuals need not be re-vaccinated as is the case following a fully myeloblative regimen. (Dr. Burt has published his reasoning for why the MIST protocol does not require re-vaccination as follows: "[For the non-myeloablative MIST protocol] Autoreactive memory cells survive and autoantibodies, while significantly diminished, generally remain positive.") This tells me that the body's immune system is not completely reset [for the MIST non-myeloablative protocol] and still recognizes points of attack of the human body. To me this seems like the "possible" (but not definite) Achilles heel of MIST. So in the end, I think the HALT-MS protocol might possibly have a better chance of lifetime cure success [since BEAM treatment also requires the surrogate indicator of disease re-vaccination not required in MIST], albeit with a (only slightly) higher probability of mortality. This is why I have chosen the HALT-MS protocol, which utilizes a BEAM protocol (BEAM an acronym for the four major types of chemo drugs used for the ablative process extensively used to treat certain forms of cancer). If interested you can read about BEAM here:

Before signing off today I should mention regarding other forms of stem cell therapy that are offered in an overseas unregulated market environment. There are many companies offering stem cell therapies that collect stem cells from adipose fat tissue, bone marrow and other sources, and then do an IV infusion and/or intrathecal injections. The theories cited for these treatments are usually valid, but from what I have learned not a single such "stem cell procedure" of this type has shown any reproducible clinical evidence for curing MS. Probably the downside risk is small for these therapies, but the upside usually fails to materialize and can be drowned out by the marketing hype of these companies (which is why these therapies are not available in the United States due to FDA restrictions). I feel sorry for people that get sucked into these programs that offer little clinical benefit beyond a placebo effect. And I feel especially bad for anyone seeking such a treatment in lieu of the true cure of a stem cell (bone marrow) transplant. [Post transplant note: Another way to think about this is "No chemo = No cure." This is because just injecting stem cells into one's body does nothing to correct the underlying defective autoreactivity of the body's immune cells that are causing the MS damage. MS disease progression needs to first be halted before meaningful nerve repair/compensation can take place.]

For now I'm getting ready to spend time with my wonderful relatives for a nice Thanksgiving and will depart for Germany next Monday, November 30. In my next post I'll let you know more about what I've done to prepare for my trip and the procedure. Getting phsyched up!

Thanks so much for following along with me!

- George