The Science Behind Stem Cell Transplantation

Not my normal post, but I thought many would be interested in more of the scientific information of HSCT, so with the permission of George Goss I am able to provide the below information.  It’s a lot to take in, so you may need to read it a few times, and I encourage you to watch the videos provided as well.


The Science Behind Stem Cell Transplantation to cure MS
By: George Goss

There is currently only one scientifically-demonstrated & confirmed treatment for Multiple Sclerosis with enduring curative efficacy:Hematopoietic Stem Cell Transplantation (HSCT). This is not a new medical procedure; it has been performed millions of times all around the world since the 1960’s for treatment of cancer (now approximately 50,000 times per year) and has been used successfully to cure several types of hematologically-rooted autoimmune disorders since the early 1990’s (such as MS, scleroderma, rheumatoid arthritis, lupus, CIDP and others). It involves chemotherapy so the treatment is both uncomfortable and expensive (most medical insurance will not yet cover it for treatment of an autoimmune disorder until the phase III clinical trial is completed later this decade, or the beginning of the next). It is not an impossible procedure to endure, as many people do it (including me) and make it through just fine. But this procedure is currently the ONLY treatment that has been scientifically verified to stop the underlying MS disease process, restore normal immune self-tolerance and produce lasting curative symptomatic improvement for the majority of MS patients, as it has for me and others. And definitely worth mentioning. . . . probably one of the biggest intangible benefits to stopping the MS disease progression is that this treatment restores a degree of certainty to the future of a person’s life that MS often robs us of. To me this has been worth more than gold. Beyond this the only outstanding question of relevance here. . . . How much is a cure for MS worth to you in terms of time, inconvenience and money? Something that can only be answered by each individual.

The reason you probably have not previously heard of this treatment and it’s curative effect on MS is because it is still a rather uncommon procedure for treatment of autoimmune disorders. But that is changing. As of 2008 there were a cumulative total of 400 people worldwide that had undergone HSCT for the treatment of MS. Admittedly that’s not a huge number. But by 2010 that number had jumped an additional 20% to 500 people treated worldwide for MS, and a total of about 1000 for all autoimmune diseases combined with the number continuously climbing. (As of 2012 the numbers are closer to 1000 treated for MS, and closer to 2000 for all autoimmune diseases combined.) So it is just now starting to gain more traction and acceptance by the broader medical community for the treatment of MS. I’m probably the first person from North America to have the procedure completed outside of a clinical trial or study to cure my MS. But just wait until the phase III clinical trials are complete later this decade, or early the next. Then the numbers will quickly jump into the many thousands. I guarantee it!

This table (I borrowed from Dr. Dimitrios Karussis of Haddasah-Hebrew Medical Center) shows the total number of people with autoimmune disorders (including MS, scleroderma, rheumatoid arthritis, lupus, juvenile arthritis and others) worldwide that have undergone HSCT over time for the treatment of their specific disorder:

One of the most compelling reasons in support of HSCT as a cure for MS is that when you read the various & substantial foundation clinical science data it is very consistent across studies and trials. Not just a little consistent, but extremely consistent. Such reproducibility is the gold standard of science and is what really tipped my thinking overwhelmingly in favor of pursuing HSCT to successfully & completely stop my MS disease activity.

But before cutting over to reading all the science, it is important to mention this critical point. . . . . Looking at the global studies to date and building on the clinical experience and knowledge developed so far, it is well understood that people treated earlier in the MS disease cycle as opposed to later fare much better with curative HSCT treatment results. Individuals that have RRMS with a fully ambulatory Expanded Disability Status Score (EDSS) experience essentially 100% halting of their MS disease activity (my personal definition of a cure), and then on top of this better than 80% of the same group of people actually experience significant reversal (improvement) of their MS-related disability and symptoms. In effect, not a single person treated during this earlier(ambulatory) MS stage appears to experience symptomatic worsening following hematopoietic stem cell transplantation, but instead have an excellent chance of reversing their existing disease symptoms (if you consider greater than >80% an excellent chance, which I do). Unfortunately the curative results are not as impressive when utilizingHSCT for treatment of patients that have a later-stage non-ambulatory progressive MS disease status. So although likely that the progression of MS disease activity will be stopped in all forms of MS (both relapsing and progressive) following HSCT, people with advanced progressive MS are unlikely to see as much overall improvement (reversal) of existing symptoms, if at all. I have created an interpolated graphical slide to categorize the expected approximate relative probability of curative efficacy and symptomatic improvement (based upon finite data from the clinical trials) following hematopoietic stem cell transplantation vs. disease status at time of treatment which clearly favors earlier treatment, as opposed to HSCT later in the disease cycle when demonstrated benefits are usually not as obvious or dramatic:

However, for the majority of people that do experience symptomatic improvement, the rate of improvement is likely not time-linear and will usually begin to slow within the initial couple of years following transplantation, following an “expected” curvilinear asymptotic slope of diminishing returns over time. That basically means that the majority of symptomatic improvement (for those that do experience improvement) will be predominantly evident in the earlier months and years following recovery from the acute chemo effects of HSCT. For the majority of people that will experience symptomatic improvement, likely it will continue going forward but at a diminished rate over time. As a general rule the curvilinear shape of this symptomatic improvement curve will likely be evident for most MS patients receiving HSCT (and is what I am personally experiencing following my own HSCT procedure). However I’m sure the precise slope of this curve will somewhat differ for each individual based upon variable factors that include the phase of disease activity (RR, SP, PP) and relative total disability at time of treatment. The curve is likely “taller” for relapsing cases and likely “flatter” for progressive cases. (click to enlarge):

And a video from my six month blog posting (when I realized that my MS disease progression was both stopped, and reversing/improving in which I describe this phenomenon that continues today more than one-and-a-half years post-transplantation. . . .

My blog is presented completely in chronological order from before I started my treatment, to after. This post page just provides reference information for those that want to know more details regarding the clinical science. If you want to know about the experience, you can start at the first page of my blog and follow along to the happy & successful ending (I originally wrote this blog for family & friends to track my progress, but I also hope this info will help others possibly interested in this cure).

And the science. . . .

It is still not understood “why” MS occurs. But it is well understood “what” is happening in individuals with MS.

As for the cause. . . The general prevailing (unconfirmed) belief among scientific professionals is that a genetically susceptible / vulnerable individual is exposed to a yet-to-be-identified environmental antagonist that initiates the neurologically-damaging immune self-intolerance of MS. I have heard the apt analogy that genetics loads the gun and the environment pulls the trigger. Clearly more elucidation is required in this area. However, here is some relevant scientifically-determined information from researchers at the University of California, Irvine pointing down this path:

Link Between Environment and Genetics in Triggering Multiple Sclerosis

New genetic clues to multiple sclerosis

Genetics and the environment converge to dysregulateN-glycosylation in multiple sclerosis

MS genetic discovery

New Genes Confirm Immune System ‘Intimately’ Involved in MS

As for the underlying MS disease process / progression, the overwhelmingly-established science and scientifically-valid data clearly indicates that the mechanistic action of the underlying MS disease pathology is that of self-intolerant autoimmunity. Most doctors / researchers now consider this as fact, not just conjecture as explained by these research scientists at Wayne State University:

Researchers publish results settling multiple sclerosis debate

“This work is significant because for the first time we are able to definitively establish a cause-and-effect relationship linking the marked T cells to the development of relapses and show unambiguously that it was the same T cells that mediated relapsing cycles””Targeting such disease-causing T-cells in MS is definitely a valid therapeutic approach that should be pursued,” Tse added.

And indeed, this is exactly what HSCT does.

How & why does HSCT cure multiple sclerosis?

As a curative treatment HSCT works by partially or completely erasing the body’s immune system memory. This effects a beneficial change of the body’s overall B- and T-lymphocyte epitope (antigen binding)repertoire, inactivating autoimmunity (making the body’s immune cells “antigen naive”) which results in restoration of immune self tolerance. This is often referred to as “resetting” the immune system which stops the underlying MS disease activity & progression. Once achieved, the body then has a chance to repair (or compensate for) existing neural damage that is not undermined by further MS disease progression, often resulting in substantial and lasting symptomatic improvement.

The interesting fact here is that it is the chemotherapy which is effecting the curative aspect of the treatment by wiping out long-lived T- and B-lymphocytes of the body that carry the faulty autoreactive memory so they may be replaced by naive, unprogrammed and self-tolerant non-autoreactive lymphocytes generated by the bone marrow. The stem cells themselves are not the specific reason for the curative effect of this treatment. The re-infusion of the hematopoietic stem cell graft is simply for the purpose of re-establishing the bone marrow which has been ablated as part of the chemotherapy conditioning. So in effect, the stem cells are not curing the patient of MS, but are instead “rescuing” the patient from possible mortality as a result of the curative chemo conditioning regimen. This is why the stem cell graft is sometimes referred to as “stem cell rescue.” It’s just rescuing the patient from near certain death (for myeloablative protocols) due the treatment and adding an extra measure of a safety factor for non-myeloabltive protocols.

The takeaway concept here is no chemotherapy = no cure. This is why simply injecting stem cells into the body does not render the body’s immune system self-tolerant as is required to stop the underlying MS disease activity. Sorry. No free lunch here.

And the clinical data. . . . .

Clinical research into HSCT as a treatment for autoimmune diseases (and MS specifically) began in earnest approximately 20 years ago in the early 1990’s in Europe. Here is an early report of a retrospective compilation of many of these clinical data:

University of Basel, Basel, Switzerland – Immune ablation and stem-cell therapy in autoimmune disease Clinical experience (published 2000)

Click to access ar102.pdf

And here is an updated paper from the same group regarding the current (published 2010) status. . . . .

Hematopoietic Cell Transplantation for Autoimmune Disease: Updates from Europe and the United States

Then in the 19990’s Dr. Richard Burt (formerly with the US NIH and currently a researcher at Northwestern University Feinberg school of medicine, Chicago) whom became interested in the work began the first US-based HSCT clinical trial work with myeloablative hematopoietic stem cell transplantation (HSCT) for MS. He later (collaborating with Prof. Shimon Slavin) worked to find a way to maintain the efficacy and to reduce the (then) mortality of the treatment by switching to astrongly-lymphotoxic (and milder myelotoxic) chemotherapy protocol with either (Fludarabine + Cyclophosphamide or Campath-1h) or an alternate therapy of a combination of (Cyclophosphamide + Anti-Thymocyte Globulin (rATG)) which does not kill off 100% of the bone marrow; reducing the period of time the patient must survive with degraded (not ablated) immune function and a corresponding risk reduction of possible infectious treatment complications. This work continues today with the completion & evaluation of a NIH/FDA phase II Clinical Trial and an ongoing randomized phase III trial with very good consistent curative results.

A graph I created that shows a comparison of the relative engraftmentrecovery profile and corresponding innate-basic immune function recovery for both myeloablative and non-myeloablative (lympoablative) protocols:

Dr. Richard Burt, Northwestern University Feinberg School of Medicine, Chicago:

WHO WE ARE: Richard K. Burt, MD

DIAD (Division of Immunotherapy and Autoimmune Diseases), NWUChicago, IL

To watch videos about the work at the Division of Immunotherapy and Autoimmune Diseases (DIAD), please click on the link below to access an assortment of informative videos:

JAMA Report – Dr. Richard Burt video; stem cell use improves the lives of Multiple Sclerosis sufferers

Turning the tide on multiple sclerosis

Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study

Lupus and MS Treatment with Adult Stem Cells with Dr. Richard Burt – ABC News Video (watch past the Lupus patient to see the MS patient treated with HSCT)

Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease

Turning the tide on multiple sclerosis

Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Click to access artigo113.pdf

Treating MS Symptoms With Stem Cells

Hematopoietic stem cell transplantation for autoimmune diseases: What have we learned?

Click to access YJAUT_1067_1.pdf

Phase II FDA trial – MIST (Multiple sclerosis International Stem cell Transplant) phase II clinical trial – Hematopoietic Stem Cell Therapy for Patients With Multiple Sclerosis

Phase III FDA randomized clinical trial – Stem Cell Therapy for Patients With Multiple Sclerosis Failing Interferon A Randomized Study

Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant (Autoimmune) Diseases [also lists relevant clinical trials and overall results summary on page 4]

Click to access JAMA_ASC_review.pdf

Multiple Sclerosis Treatment with Adult Stem Cells

Stem cells to treat MS – MSRA Public Lecture – A/Prof Richard Burt

Part 1 -

Part 2 -

Part 3 -

Shortly following some of the initial work done by Dr. Burt, Dr. Richard Nash, a noted immunologist at the Fred Hutchinson Cancer Research Center in Seattle (where early bone marrow transplantation was pioneered in the US in the late 1960’s) also became interested in HSCT as a means to treat autoimmune diseases. He has already completed several studies and a phase I clinical trial (separate from Dr. Burt’s work). He is currently running a myeloablative HSCT phase II clinical trial (all patients have already been treated) called HALT-MS (listed below, and is also substantially similar to the same treatment protocol that I received). He will soon be starting the randomized phase III clinical trial for the myeloablative (BEAM) protocol.

Dr. Richard Nash, Immunologist, Fred Hutchinson Cancer Research Center, Seattle:

Bio / profile:

Patients with autoimmune diseases are finding success with treatments originally developed to fight cancer

And an excellent overview of the MS treatment they have developed (and which I received). . . Stem Cell Transplantation in Patients With MS in the HALT Trial

And a peek into (Feb 2011) update on the clinical status of a few of the typical patient’s status (that basically says that all MS disease activity & progression continues to be stopped four years following the transplant procedure):

Click to access poster_msc_HALTMS_aan.pdf

And a top level overview of the total (phase II) post-treatment population:

Click to access poster_other_HALT-MS.pdf

An older paper that reflects the much earlier (and is now less relevant compared to the current phase II/III clinical trial data) work that I provide for historical purposes – High-Dose Immunosuppression and Hematopoietic Stem Cell Transplantation in Autoimmune Disease: Clinical Review

Click to access BBMT.8.5.Openshaw.PDF

HALT-MS phase II clinical trial – High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) Study

HALT-MS clinical trial website:

Neurology Reviews – Can Immune System Transplants Halt MS?

By the way, the following link is of a nice (short) video of Dr. E. Donnall Thomas’ Legacy of being the first pioneer to successfully perform bone marrow / stem cell transplantation on human beings for treatment of cancer at The Fred Hutchinson Cancer Research Center in Seattle. He deservedly won the Nobel prize in Medicine in 1990 for his work in this field that has directly led to to HSCT for auto immune disorders:

Dr. Burt’s approach is lymphoablation with autologous HSCT transplantation. Dr. Nash’s approach is myeloablation with autologous HSCT transplantation (the protocol I received). The University of Louisville is currently doing a phase I/II study of myeloablation with allogeneic HSCT transplantation with mixed chimerism (i.e. mixing & infusing of differing amounts of both donor and recipient stem cells together for grafting). All three phase II studies in the US to date have already completed all patient transplantations and no one has died as a result of the procedure. Now that the treatments are complete the lengthy & involved follow-up work is being done now to evaluate the patient outcomes. This will of course take several more years until final reports are published. All these programs have already designed the phase III studies and have submitted the program plans to the FDA for approval. Currently Dr. Burt’s MIST program in Chicago is in active randomized phase III patient selection & treatment with others coming online soon.

University of Louisville Phase I/II Clinical Trial – Donor Stem Cell Transplantation (with variable mixed chimerism [mixing both donor and recipient stem cells together prior to engraftment]) for the Treatment of Multiple Sclerosis

There is also a stem cell transplantation study in Ottowa, Canada completed by Dr. Mark Freedman that is currently closed because it has completed treatment of all planned study participants, but currently treats (Canadian) patients outside of clinical trial work. This is an especially relevant scientifically-oriented study because it incorporated a very important control (randomized) arm in the study:

Clinical trial info: Autologous Stem Cell Transplant for Multiple Sclerosis (MS/BMT)

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

Ottowa Hospital-sponsored stem cell & transplantation lecure video: MS and Stem Cells: It’s happening right now

Part 1 –

Part 2 –

Part 3 –

And there is also clinical treatment being conducted in Australia by Dr. Colin Andrews at Canberra Hospital that is also using a BEAM treatment protocol:

Canberra Hospital cures MS?

Mother Carmel Turner is first Australian woman to undergo stem cell transplantation for MS (an especially wonderful story because HSCT allowed her to walk again after having been confined to a wheelchair for the previous two years):

Mum’s [Carmel Turner] amazing recovery from MS

Finally, I Can Be A Mum (overview story of Carmel)
Carmel Turner’s website: Carmel Turner Adult Stem Cell Treatment for Multiple Sclerosis

And here is Carmel Turner’s You Tube video channel where she has posted videos regarding her HSCT (and just like myself, she appears to be very happy to no longer take medication to treat her MS since her undelying MS disease activity has stopped)

Teen walks after MS stem cell treatment

Stem cell treatment reverses effects of MS

Other information of relevance (in no particular order):

Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation (HSCT)

[I especially appreciate this statement from this specific report. . . “Before HSCT, 61 relapses occurred in 82 patient months; during follow-up, one relapse in 289 patient months.” If you need a slap in the face of the reality of HSCT to cure MS, here is a scientific study report that confirms the data]:

No proinflammatory signature in CD34+ hematopoietic progenitor cells in multiple sclerosis patients [this well-authored paper goes on to make the important conclusion “Our results support the use of aHSCT for treatment of MS.”]

Autologous hematopoietic stem cell transplantation in multiple sclerosis [includes HSCT treatment results for both relapsing and progressive patients]….i

Autologous HSCT for severe progressive Multiple Sclerosis in a multicenter trial: impact on disease activity and quality of life
Hemopoietic Stem Cells Safe, May Reverse Neurologic Disability in RRMS

Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Diseases

Immune ablation and stem-cell therapy in autoimmune disease: Clinical experience

Immune Ablation and Autologous Stem Cell Transplantation for Aggressive Multiple Sclerosis: Presented at ECTRIMS

Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis

Bone Marrow Transplantation Study Update: Participants Treated in Study to Stop MS Progression

New hope for MS sufferers – Ottawa doctors to try bone marrow transplants to treat debilitating disease

Bone Marrow Transplant Shows Promise for MS

Study of bone marrow stem cells in multiple sclerosis

Immune ablation and stem-cell therapy in autoimmune disease Introduction

Click to access ar100.pdf

Barry Goudy, successfully treated with adult stem cells for Multiple Sclerosis testifying in front of a United States Congressional hearing on the use of adult stem cells:

Stem cell transplantation in multiple sclerosis: current status and future prospects

Click to access nrneurol.2010.35.pdf

Clinical and MRI outcome after autologous hematopoietic stem cell transplantation in MS

Click to access Stem%20cell%20transplant.pdf

Aggressive multiple sclerosis – is there a role for stem cell transplantation?

A brief article summarizing the results of a phase I HSCT clinical trial that focussed treatment of progressive patients with high EDSS scores.

MS Researchers Share Progress at Annual ECTRIMS [European Committee for Treatment and Research in Multiple Sclerosis] Conference (October 13-16, 2010)

High Time for HiCy?

Stem Cell Transplantation Clinical Study Data for Historical Perspective

Data out of Russia that provides a good overview of HSCT stratified by MS disease type (which indicates good efficacy for all types of MS cases):

Rebooting the Immune System [with Cyclophosphamide]

Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review

Stem cell transplantation for autoimmune diseases

Three strategies of Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Autologous haematopoietic stem cell transplantation for secondary progressive multiple sclerosis: an exploratory cost-effectiveness analysis

Autologous stem cell transplantation for progressive multiple sclerosis: Update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database

Click to access sclerosi-multipla.pdf

Patient-Reported [Quality of Life – QoL] Outcomes in Multiple Sclerosis Patients Undergoing Autologous Stem Cell Transplantation

The Lancet publisher contacted me to ask if I would include a link to their website publications portal regarding MS (and neurological issues in general). The Lancet maintains sound scientific standards and ethically responsible publications and I am happy to list thier website publications portal link for your perusal (and they also list technical articles for hemotopoietic stem cell transplantation for MS relevant to my own blog). Also as explained by the publisher, “Your visitors will be able to listen to free podcasts for author interviews and expert discussions covering international issues relevant to (MS) neurology. Here, individuals can learn more through our direct links to free resources such as reviews, opinions, and news throughout the Lancet online community.”. . . .

Last tangential note. . . . . Although it works well for Multiple Sclerosis (and several other autoimmune disorders), an autologous hematopoietic stem cell transplant will not cure every disease. However, it has been shown to have similar (good-to-excellent) curative results for other hematologic-based autoimmune diseases. If I were otherwise afflicted with any of these other types of hematologic-based autoimune disorders (there are likely many more than I have listed here), I would consider seeking the same transplant procedure myself to cure it:

– Rheumatoid arthritis
– Scleroderma (Systemic Sclerosis)
– Inflammatory Bowel Disease (Chrohn’s disease, ulcerative colitis)
– Systemic Lupus Erythematosus (SLE)
– Polymyositis – Dermatomyositis – Evans syndrome
– Hashimoto’s thyroiditis
– Chronic inflammatory demyelinating polyneuropathy (CIDP)
– Graves’ disease
– Autoimmune hemolytic anemia
– Autoimmune blistering diseases
– Autoimmune lymphoproliferative syndrome
– Myasthenia gravis
– Psoriatic arthritis
– Wegener’s granulomatosis
– Sjögren’s syndrome (Mikulicz disease, Sicca syndrome)
– Churg-Strauss syndrome
– Microscopic polyangiitis
– Relapsing polychondritis
– Pemphigus vulgaris
– Sarcoidosis
– Ankylosing spondylitis
– Diabetes mellitus type 1 (but only if HSCT is performed within several months following disease onset)
– Sickle Cell Disease can be cured with a similar HSCT procedure utilizing mixed chimerism with a partial-match HLA doner

Dr. Richard Burt On the topic of HSCT as curative treatment for a wide range of autoimmune disorders:

If you know someone with one of these diseases you may want to let them know about the possibility of a hematopoietic stem cell transplantation procedure as a means to arrest/correct/reverse the progression of the disease so they can make up thier own mind regarding treatment options.