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Bone Marrow Stem Cells

  1. Intense ImmunoSuppression followed by Autologous Stem Cell Transplantation in severe Multiple Sclerosis
    Neurol Sci 2005 Dec;26 Suppl 4:S200-3

  1. Hematopoietic Stem Cell Transplantation In Multiple Sclerosis
    Bone Marrow Transplant, 1998 Mar, 21:6, 537-41

  2. High-dose immunosuppression and Autologous Hematopoietic Stem Cell rescue for Severe Multiple Sclerosis
    J Hematother Stem Cell Res 2003 Dec;12(6):701-11

  3. Immune ablation and Stem-Cell therapy in Autoimmune Disease. Clinical experience
    Arthritis Res 2000;2(4):276-80




#1

T-Cell-Depleted Autologous Hematopoietic Stem Cell Transplantation In Multiple Sclerosis

Burt RK; Traynor AE; Cohen B; Karlin KH; Davis FA; Stefoski D; Terry C; Lobeck L; Russell EJ; Goolsby C; Rosen S; Gordon LI; Keever Taylor C; Brush M; Fishman M; Burns WH
Bone Marrow Transplant, 1998 Mar, 21:6, 537-41
Northwestern Univ, Medical School, Dept of Medicine, Chicago, IL, USA
UI# 98202055
Abstract

Multiple Sclerosis (MS) is a disease of the Central Nervous System characterized by Immune-Mediated destruction of Myelin.

In patients with Progressive deterioration, we have intensified ImmunoSuppression to the point of MyeloAblation. Subsequently, a new Hematopoietic and Immune System is generated by infusion of CD34-positive Hematopoietic Stem Cells (HSC).

Three patients with clinical MS and a decline of their Kurtzke Extended Disability Status Scale (EDSS) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS of 8.0 at the time of enrollment were treated with Hematopoietic Stem Cell (HSC) transplantation.

Using a MyeloAblative conditioning regimen of Cyclophosphamide (120 mg/kg), MethylPrednisolone (4 g) and total body irradiation (1200 cGy).

Reconstitution of hematopoiesis was achieved with CD34-enriched Stem Cells. The average time of follow-up is 8 months (range 6-10 months). Despite withdrawal of all ImmunoSuppressive medications, functional improvements have occurred in all three patients.

We conclude that T-Cell-depleted Hematopoietic Stem Cell Transplantation can be performed safely in patients with severe and debilitating Multiple Sclerosis.

Stem Cell Transplantation has resulted in modest Neurologic improvements for the first time since onset of Progressive disease although no significant changes in EDSS or NRS scales are evident at this time.



#2

High-Dose ImmunoSuppression And Autologous Hematopoietic Stem Cell Rescue For Severe Multiple Sclerosis

Fassas A, Kazis A
J Hematother Stem Cell Res 2003 Dec;12(6):701-11
Aristotle University Medical School, George Papanicolaou Hospital, Department of Hematology, Thessaloniki, Greece
PMID# 14977479
Abstract


Multiple Sclerosis is a relatively common and seriously disabling disease of Autoimmune Pathogenesis, for which there is currently no cure.

Available therapies include ImmunoModulating agents and standard-dose ImmunoSuppressants, which may be helpful but are not curative.

Recently, studies in animal models have indicated that control of Autoimmune Disease can be obtained by high-dose ImmunoSuppression followed by Hematopoietic Stem Cell Transplantation (rescue).

Autologous transplants for severe and refractory Multiple Sclerosis were proposed in 1997 and have been performed ever since in selected patients and in the context of Phase I/II trials.

To date, more than 200 patients have been treated worldwide, and similar results were obtained in different centers:

High-dose therapy suppresses inflammation in the Brain to a degree superior to any other conventional therapy and seems to delay significantly clinical disease progression.

There is, however, a procedure-related mortality risk of 1.5-5%, requiring careful patient selection before transplant.

The treatment should be reserved for patients having high chance of response, i.e., young patients with low disability scores but rapidly progressing disease, having Inflammatory rather than NeuroDegenerative changes in the Central Nervous System.

The mechanism of action of transplantation is unclear.

The initial concept of Immune ablation by high-dose therapy and reconstitution of normal Immunity from transplant-derived Lymphocyte progenitors has given way to the concept of "resetting" the Immune System and of bringing the disease to a lower level of activity.

One could also speculate on a tissue repair effect, given the ability of human Hematopoietic Stem Cells to migrate also into the Central Nervous System. The clinical effect of transplantation remains to be demonstrated in a randomized study.

The Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation has launched such a trial, comparing transplantation to the currently best available therapy, i.e., Mitoxantrone.

And, in about 5 years we should know whether transplantation offers more than the benefit of a transient ImmunoSuppressive effect.



#3

Immune Ablation And Stem-Cell Therapy In Autoimmune Disease. Clinical Experience

Tyndall A, Gratwohl A
Arthritis Res 2000;2(4):276-80
University of Basel, Department of Rheumatology, Basel, Switzerland
PMID# 11094441
Abstract

In the past 5 years, around 350 patients have received Haematopoietic Stem Cell (HSC) transplantation for an Autoimmune Disease.

With, 275 of these registered in an international data base in Basel under the auspices of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation(EBMT).

Most patients had either a Progressive form of Multiple Sclerosis (MS; n = 88) or Scleroderma (now called Systemic Sclerosis; n = 55).

Other diseases were Rheumatoid Arthritis (Ra n = 40), Juvenile Idiopathic Arthritis (JIA; n = 30), Systemic Lupus Erythematosus (SLE; n = 20), Idiopathic Thrombocytopenic Purpura (ITP; n = 7) and others.

The procedure-related mortality was around 9%, with between-disease differences, being higher in Systemic Sclerosis and JIA and lower in RA (one death only).

Benefit has been seen in around two-thirds of cases. No one regimen was clearly superior to another, with a trend toward more infectious complications with more intense regimens.

Prospective, controlled randomized trials are indicated and being planned.



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