Wednesday, June 23, 2010

The Science Behind Stem Cell Transplantation to cure MS


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 (click to enlarge):


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 utilizing HSCT 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 (click to enlarge):

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. . . .

http://www.youtube.com/watch?v=jFQr2eqm3Cg

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

http://www.sciencedaily.com/releases/2011/05/110531115313.htm

New genetic clues to multiple sclerosis

http://www.webmd.boots.com/news/20110812/new-genetic-clues-multiple-sclerosis

Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis

http://www.nature.com/ncomms/journal/v2/n5/full/ncomms1333.html


MS genetic discovery

http://www.ctv.ca/CTVNews/Health/20110811/ms-gene-study-immune-system-110811/

New Genes Confirm Immune System 'Intimately' Involved in MS

http://www.medscape.com/viewarticle/747957

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


http://research.wayne.edu/communications/news-release.php?id=191&y=&m

"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)

http://www.biomedcentral.com/content/pdf/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

http://www.ncbi.nlm.nih.gov/pubmed/19895895

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 a strongly-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 engraftment recovery 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

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

DIAD (Division of Immunotherapy and Autoimmune Diseases), NWU Chicago, IL

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

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:

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

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

http://www.youtube.com/watch?v=Y8SAgUB5hQs

Turning the tide on multiple sclerosis

http://abclocal.go.com/wls/story?section=news%2Fhealth&id=6656336

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

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(09)70017-1/fulltext

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)

http://www.youtube.com/watch?v=AZ5XQA-EvVY

Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease

http://theoncologist.alphamedpress.org/cgi/content/full/4/1/77

Turning the tide on multiple sclerosis

http://abclocal.go.com/wls/story?section=news/health&id=6656336

Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

http://pegasus.fmrp.usp.br/projeto/artigos/artigo113.pdf

Treating MS Symptoms With Stem Cells

http://www.cbsnews.com/stories/2009/02/10/earlyshow/main4789551.shtml?

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

http://www.allmystemcells.com/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

http://www.clinicaltrials.gov/ct2/show/NCT00278655

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

http://clinicaltrials.gov/ct2/show/NCT00273364?term=burt+and+multiple+sclerosis&rank=2

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]

http://www.allmystemcells.com/JAMA_ASC_review.pdf

Multiple Sclerosis Treatment with Adult Stem Cells

http://www.frcblog.com/2009/12/multiple-sclerosis-treatment-with-adult-stem-cells/

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

Part 1 -http://www.youtube.com/watch?v=s3TgPFy1Ozo&feature=related

Part 2 -http://www.youtube.com/watch?v=msYTOSo4jZo&feature=channel

Part 3 -http://www.youtube.com/watch?v=8mUwCvSWD14&feature=channel

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:

http://www.seattlecca.org/doctor/richard-a-nash.cfm

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

http://www.fhcrc.org/about/pubs/quest/articles/2003/03/autoimmune.html

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

http://www.unitedspinal.org/msscene/2009/05/06/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):

http://www.bcm.edu/neurology/pdf/poster_msc_HALTMS_aan.pdf

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

http://www.bcm.edu/neurology/pdf/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

http://static.cjp.com/gems/bbmt/BBMT.8.5.Openshaw.PDF

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

http://clinicaltrials.gov/ct2/show/NCT00288626?term=MS+stem+cell+transplant&rank=1

HALT-MS clinical trial website:

http://www.halt-ms.org/

Neurology Reviews – Can Immune System Transplants Halt MS?

http://www.neurologyreviews.com/aug06/immune.html

By the way, here is 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:

http://www.youtube.com/watch?v=6Y_j8_2nhMU

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

http://www.clinicaltrials.gov/ct2/show/NCT00497952

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:

http://www.ohri.ca/profiles/freedman.asp

http://mssociety.ca/en/research/meddmmo-bonemarrowstudy-feb05.htm

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

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

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

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

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

Part 1 - http://www.youtube.com/watch?v=LGvnZpYKLsE&feature=related

Part 2 - http://www.youtube.com/watch?v=4UG4jgnvjMQ&feature=related

Part 3 - http://www.youtube.com/watch?v=e4kmQ6v_8Yw&NR=1

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:

http://health.act.gov.au/c/health?a=&did=10246388

Canberra Hospital cures MS?

http://the-riotact.com/canberra-hospital-cures-ms/21720

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):

http://www.youtube.com/watch?v=KEHgwPmKwBM&feature=context&context=C3de6fa1ADOEgsToPDskLRSijXO32W56aWd_L5nf4F


http://www.adelaidenow.com.au/news/national/carmel-turners-magic-cure/story-e6frea8c-1226004742545

Mum's [Carmel Turner] amazing recovery from MS

http://www.heraldsun.com.au/ipad/mums-amazing-recovery-from-ms/story-fn6bfmgc-1226063636658

Finally, I Can Be A Mum (overview story of Carmel)

http://au.lifestyle.yahoo.com/new-idea/real-lives/stories/article/-/9542086/finally-i-can-be-a-mum/

Carmel Turner's website: Carmel Turner Adult Stem Cell Treatment for Multiple Sclerosis

http://www.msstemcell.com/

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)

http://www.youtube.com/user/camelbturner1

Teen walks after MS stem cell treatment

http://www.abc.net.au/local/stories/2009/12/14/2770762.htm

Stem cell treatment reverses effects of MS

http://www.abc.net.au/pm/content/2009/s2771501.htm

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]:

http://msj.sagepub.com/content/15/2/229.abstract

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."]

http://www.ncbi.nlm.nih.gov/pubmed/22252466

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

http://www.ctt-journal.com/index.php?id=164....i

Autologous HSCT for severe progressive Multiple Sclerosis in a multicenter trial: impact on disease activity and quality of life

http://bloodjournal.hematologylibrary.org/content/105/6/2601.long#REF22

Hemopoietic Stem Cells Safe, May Reverse Neurologic Disability in RRMS

http://www.medscape.com/viewarticle/587606

Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Diseases

http://www.nature.com/bmt/journal/v32/n1s/full/1704096a.html

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

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC130009/?tool=pubmed

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

http://www.pslgroup.com/dg/2161ce.htm

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

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117419/

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

http://mssociety.ca/en/research/meddmmo-bonemarrowstudy-feb05.htm

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

http://www.mult-sclerosis.org/news/Aug2000/BoneMarrowTransplantsForMS.html

Bone Marrow Transplant Shows Promise for MS

http://www.medpagetoday.com/Neurology/MultipleSclerosis/12662

Study of bone marrow stem cells in multiple sclerosis

http://www.physorg.com/news110034720.html

Immune ablation and stem-cell therapy in autoimmune disease Introduction

http://www.biomedcentral.com/content/pdf/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:

http://www.stemcellresearch.org/testimony/video/goudy.wmv

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

http://www.nature.com/nrneurol/journal/v6/n5/pdf/nrneurol.2010.35.pdf

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

http://www.direct-ms.org/pdf/DrugsMS/Stem%20cell%20transplant.pdf

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

http://www.springerlink.com/content/v0111u12230u6118/

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

http://www.sciencedaily.com/releases/2002/04/020417070731.htm

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

http://mssociety.ca/en/research/medmmo_20101102.htm

High Time for HiCy?

http://www.hopkinsmedicine.org/hmn/w08/feature1.cfm

Stem Cell Transplantation Clinical Study Data for Historical Perspective

http://reocities.com/Hotsprings/3468/stemcell.html

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):

http://www.stemcellms.ru/doklad06.php


Rebooting the Immune System [with Cyclophosphamide]

http://www.youtube.com/watch?v=SuJj52twOdo&feature=related
Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review

http://msj.sagepub.com/content/17/2/204

Stem cell transplantation for autoimmune diseases

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817019/


Three strategies of Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

http://www.stemcellms.ru/doklad06.php


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

http://www.nature.com/bmt/journal/v45/n6/full/bmt2009305a.html


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

http://www.futurehealthbiobank.it/uploads/IT/articoli_staminali/sclerosi-multipla.pdf

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


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

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.". . . .


http://www.thelancet.com/collections/neurology?collexcode=115&subcollexcode=115109


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
- Stisff Persons Syndrome (SPS)
- 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:

http://www.youtube.com/watch?v=yi49gJkuRlQ

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.

18 comments:

  1. I'm trying to have a stem cell transplant done either in Seattle or Chicago via one of the studies. The issue is insurance and funding. I know it's the only cure, and I'm terrified of what will happen if I don't.

    ReplyDelete
  2. Hi Lori,

    My congratulation and respect for you deciding to take control of your MS, instead of the other way around.

    I completely understand your concern. . . . unfortunately both trials in the US are very expensive (last I heard well over $200K for Seattle's HALT and close to $150K for Chicago's MIST). It's especially concerning since the majority of participants must pay on their own. However, overseas treatments may be a less-costly alternative, if it were to come to to that. Likely less than half the price.

    Stay strong! Once completing the transplantation procedure you can likely look forward to a life of progression-free MS. And improvement on top of that!

    I hope you will have the opportunity to keep me updated.

    My very best regards to you and your family,

    George

    ReplyDelete
  3. George: thank you for hosting this site. My 21 year old son was recently diagnosed after experiencing optic neuritis & MRI confirmation. Do you know if the University of Basel, Switzerland's program is as effective as Dr.Burt's? Do you know the cost?

    We are determined that our son receive treatment sooner rather than later.

    Best regards,
    Debbie

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  4. Hi Debbie, I'm sorry to hear about your son's recent diagnosis of MS. However, if your son is interested in HSCT as a treatment option, then the diagnosis being "recent" is a good thing since HSCT performed as early as possible following RR diagnosis portents the absolute best probability of completely curing his MS! Also, I'm sorry if my posting has caused some confusion. . . . I am not aware of the University of Basel doing any MS (or other) treatment involving HSCT. I only know of their retrospective study compilation technical papers based upon various studies of HSCT from around the world that I have listed on this page. As far as treatment locations go I can only comment regarding treatment details from the Heidelberg University Hospital where I had my own treatment performed (I had a very good experience). My total cost ended up being approximately 55,000 Euros plus approximately $10,000 for travel and housing costs from California. All told it came to about half the cost of treatment in Dr. Burt's clinical trial here in the US. But I'm sure there must be other places (hospitals) around the world that will also perform the procedure for those with MS. I believe the Apollo Hospital Network in India will do it. And I'm confident that the final price tag will be less than what my own treatment cost me. This is where your own research will be very beneficial. Interesting you ask about treatment efficacy. . . that's an excellent question that I am surprised I am not asked about more often. Dr. Burt's MIST treatment protocol is "Lymphoablative" (eliminates reactive T-cells but does not completely wipe out the bone marrow stem cells). The treatment I had was "myeloablative" (completely wipes out the bone marrow stem cells prior to autograft re-infusion & engraftment). To date both protocols have shown substantially similar (very good) curative results at several years out from treatment. The open question in my own mind is "how long will these two different therapies result in stopping the progression of the MS disease activity?" Is it lifetime, or only temporary? Only the continuing population study over a longer period of time will actually tell us the answer with the greatest degree of confidence. However, I decided to go with a myeloablative therapy instead of the lymphoablative therapy for one simple reason. . . . myeloablation results in total loss of immune memory via the surrogate indicator that people lose childhood immunity and require re-vaccination. Dr. Burt's lymphoablative protocol does not require re-vaccination for childhood diseases. My own theory on this is that lymphoablation does not actually completely 100% reset the body's underlying defective autoreactivity that causes MS, and makes me fearful that the treatment "might" not result in a lifetime cure. But this is only my fear, as I have no data or evidence to suggest that this is actually the case as my assumption might very well be wrong. But for my own treatment I decided to be overly conservative to ensure the best possible chance (in my own mind) that I was receiving the best chance of a lifetime cure of my MS with a myeloablative (BEAM) protocol. Regardless of the final results with Dr. Burt's lymphoablative treatment, I believe that I have most likely achieved an enduring lifetime cure with the protocol I received. So far, so good. My sincerest best wishes for your son’s good health! George

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  5. Hi George,
    First of all thank you for taking the time to put down your experience with hsct. I have been searching for details on stem cells, and your info was very detailed. Diagnosed with progressive ms with relapes at Mayo last month. Initial diagnosis was RRMS from a local nuerologist. I have made the decision to move forward with the hsct asap. Any info you can give to speed this process would be greatly appreciated. I am located in Wisconsin and willing to travel anywhere. I have been told to go to a "clean" country.
    Heidi

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    1. If you are in US & disabled you should qualify for SSDI & Medicare. Medicare covers Dr. Burt's HSCT. My husband Marc Coppins got his transplant in May 2011, so almost a year ago. See http://www.MarcStemCell.com for more info.

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  6. Hi Heidi,

    I've been having a difficult time finding available hospital facilies around the world that will perform this HSCT procedure (since it is a complex and sophisticated procedure that must be done properly to be safe). I have not checked everywhere in the world so there must be places that I am unaware of. However, I am aware of the place that I went (Heidelberg University Hospital) that will perform myeloablative HSCT for multiple sclerosis. Also, although I have no first hand experience with this facility, I understand that CTCI in Tel Aviv, Israel [http://ctcicenter.com/index.php] will perform the non-myeloablative protocol for multiple sclerosis. (So far both protocols have shown substantially similar very good curative results at several years out.) If I had my drothers (and also because a "clean" facility is high on your priority list), I personally would aim for Heidelberg's treatment since I personally think it has a better chance of lifetime cure success.

    You are welcome to e-mail me and I'm happy to share whatever information I can. My e-mail address is georgegoss@yahoo.com

    Best regards,

    George

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  7. Hi George-
    Do you know what the outcomes are on the anyone who has used the Heidelberg Hospital for the HSCT for ms? Positive and negative?
    Heidi

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  8. Hi Heidi,

    The only person that I have first-hand knowledge that went to Heidelberg to have HSCT treatment for MS is myself. The outcome is that my MS disease activity completely stopped and my pre-existing MS symptoms have improved 40%.

    Regards,

    George

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  9. Hi George,
    It's been a little over 6 months since your last entry and I am wondering how your tracking?
    I , like Carmel Turner am from Melbourne Australia and have MS . I am now considering stem cell therapy . This is against the advice of my neurologist and my own brother , who is also a neurologist , both of whom adhere to that oft stated " it's still experimental" line. I have had RRMS over past 20 years but am now experiencing a rapid decline in mobility. I need to do something now as later will be too late.
    Are you still experiencing the same benefits of the treatment ? Do you still consider it worthwhile? I am eager to hear your experience.. Ps I am an allied health professional .

    Regards

    Monique Leventer

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    Replies
    1. It is definitely worth while. Do lots of research cuz there are scams out there. If you are in US & disabled you should qualify for SSDI & Medicare. Medicare covers Dr. Burt's HSCT. My husband Marc Coppins got his transplant in May 2011, so almost a year ago. See http://www.MarcStemCell.com for more info.Good luck to you!

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  10. Hi George
    Congratulations on your success. My wife has been diagnosed for over a year now and since diagnoses has had two relapses. She has now moved to Tysabri as a treatment which she seems to be tolerating well and has shown good signs of improvement. This is best course of action for now, but in the longer term we are looking for solutions.
    HSCT is exciting but at the same time very intimidating. Thank you for such an informative blog your imformation is of great help to us who are looking for answers and dont have a decade to wait.

    Best Regards
    Kevin

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  11. Hello, George - I have some questions regarding any side effects of the chemo that was done to "wash" the stem cells before being reintroduced into your body. I was in a cladribine trial about 2 years ago, and still believe, despite the "wash out" period I was told about, that it has caused my health to deteriorate pretty rapidly in the past 18 months. If I were to get into an HSCT trial, what could I expect as chemo side effects and would they cause other physical problems?

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    1. Excellent question about the side effects of HSCT treatment, as drugs of all sorts have side effects of one type, or another. There are two distinctly different HSCT treatment protocols that have slightly different side-effect profiles; myeloablative HSCT (the same that I had) which has more side effects and non-myeloablative HSCT that has fewer side effects. However, both share the effects of temporary hair loss and temporary fatigue that lasts several months following the transplantation. I discuss in a little more detail on the following page: http://themscure.blogspot.com/2011/06/getting-into-hsct-treatment-if-you-have.html

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  12. Very nice post. I just stumbled upon your weblog and wished to say that I've truly enjoyed surfing around your blog posts. In any case I will be subscribing to your feed and I hope you write again very soon.
    Fue Hair Transplantation

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    Replies
    1. Sincerely thanks very much for your kind comments, Analisa. I plan to make some posts about relevant topics on a more frequent basis.

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  13. I am one of the Admins of a Facebook Stiff Person Syndrome (333.91) group and would like to correct the omission of our autoimmune disease from your list above. We currently have our third patient in recovery at Ottawa, one in treatment at Seattle, and another accepted and wrangling insurance for University of Michigan. One or two are in discussions with Denver. "SPS" is when the autoimmune GAD65ab that usually attacks the pancreas and causes diabetes, instead attacks neurons. Symptoms include the finest blend of MS, Parkinson's and tetanus; with the side effects of current drug treatments - heavy benzos, such as Valium, pain medications, IVIg, Plasmapheresis, or rituxibub. The disease is progressive but our early HSCT patients have reported near total recoveries.

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    1. Thanks very much, Joseph. You are absolutely correct! I have added SPS to the list of autoimmune disorders that can and does benefit from HSCT.

      There are so many more hematologically-rooted autoimmune disorders that can benefit from HSCT that I am far short of listing them all.

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