Stem Cells

　

　

Every tissue and organ in the human body is made up of different types of cells. Cells that make up skin, for example, are different from those that make up the heart. This makes it impossible for cells that make up one tissue or organ to be transferred to another tissue or organ.

However, all cells share one thing in common – they come from one cell source. In the early stages of human development, these cells can become any tissue or organ – that is, they have not yet become specialized. These cells are called stem cells.

Stem cells have two important characteristics that make them different from other types of cells. First, as noted above, all stem cells are unspecialized, and renew themselves for long periods of time through cell division. Second, under certain biochemical cues they can be made to differentiate (see below). This means that they can divide into cells with special functions, such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas.

　

Types of stem cells

Stem cells come in three forms: embryonic stem (ES) cells, embryonic germ cells, and adult stem cells. ES cells come from embryos; embryonic germ cells come from testes, and adult stem cells can come from bone marrow. Scientists work mostly with ES cells and adult stem cells.

ES cells are found in the early beginnings of human life – at the blastocyst stage of human development. This stage is from four to five days after the union of the sperm and the egg, before the embryo implants in the uterus. The 20 or so stem cells in the blastocyst are called pluripotent, which means they are capable of forming all embryonic tissues, but they cannot form a complete organism without support from the placenta.

ES cells come from embryos, fetuses, and some can come from the blood of the umbilical cord after birth.

　

Differentiation

The process by which the stem cell can become a specific cell type is called differentiation. Stem cell differentiation begins when they are exposed to certain biochemical cues – either physiological or experimental. Biochemical cues in different parts of the body stimulate stem cells to grow into the specific cells needed in that location.

　

All stem cells have the capacity to differentiate, but to different degrees.

Totipotent stem cells can become any cell in the human body;

Pluripotent stem cells can become almost any cell in the human body, but they cannot become placental tissue needed for development in the human uterus; and

Multipotent stem cells can become only a certain type of cell, such as a blood cell.

Adult stem cells are found in the fetus, child, and adult. These “adult” stem cells are found in many human tissues, such as blood, brain, intestine, skin, and muscle. They are responsible for the repair and regeneration in the body.

It was long thought that adult stem cells had less flexibility than ES cells, and that they could normally form only cell types the same as the tissue of origin. However, recent discoveries are pointing to new sources of stem cells within the adult body. Research into adult stem cells has the potential to eliminate ethical concerns about experimentation or transplantation of ES cells. The use of adult stem cells would also reduce the chance of transplant rejection because patients could receive transplants of their own stem cells.

The possibility that adult stem cells also have a greater “plasticity” than previously believed has resulted in new experimentation. For example, scientists now believe that certain types of adult stem cells can develop into cells of another tissue (for example human blood stem cells have been shown to differentiate into liver cells if the conditions are right). However, no adult stem cell has been definitively shown to be completely pluripotent.

Some scientists are now calling adult stem cells “somatic stem cells”. Unlike ES cells, which are defined by where they originated (in the inner cell mass of the blastocyst), the origin of adult stem cells in mature tissues is unknown.

Some current research

Research into adult stem cells has caused a lot of excitement. Because adult stem cells have been found in many more tissues than originally thought possible, scientists have asked whether adult stem cells could be used for transplants. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of therapies for many serious common diseases.

Some diseases have already been targeted. For example, adult blood stem cells have been used to treat hematologic (blood) cancers. Adult blood-forming stem cells from bone marrow have been used in transplants for over 30 years. The stem cells of the matched donor are purified, and the patient’s bone marrow is then destroyed by radiation and reconstituted with the stem cell graft.

Several groups have been working on animal models in which pluripotent stem cells are grafted into damaged hearts. The stem cells were shown to “beat” with the surrounding heart cells. Several animal and early human trials are also underway to use pluripotent or adult stem cells to repair damage to the nervous system, such as in spinal cord injury, Parkinson’s disease, and Alzheimer’s disease.

While large numbers of ES cells can be grown in a laboratory, adult stem cells are rare in mature tissues and a way to increase their numbers in cell culture has not yet been developed. Much research is ongoing in this area, as large numbers of cells are needed for stem cell replacement therapies.

Potential applications of human stem cells

One of the goals of scientists is to control cell differentiation. This would allow them to create any tissue or organ in the body from a single stem cell. This research involves many biotechnology applications, such as the study of stem cell genetics, biological factors (normally occurring proteins that the body needs to function normally), receptors on the stem cells and stem cell physiology. Researchers are encouraging adult stem cells, such as those from the skin, to become other types of tissue, such as nerve or muscle. Of all the adult stem cells identified so far, hematopoeitic stem cells (a stem cell from which all red and white blood cells develop) have been the most studied.

Scientists are using genetic modification to expand the potential therapeutic applications of stem cells. Stem cells can be modified to produce enzymes or factors, such as insulin, before being transplanted into the body. Stem cells can also be modified to resist certain infections. For example, studies are underway to create stem cells resistant to HIV. Once implanted, these stem cells would repopulate the diseased immune system of AIDS patients with cells resistant to the disease.

However, the main application of stem cells is still to replace damaged, diseased or dead cells. Once implanted, a stem cell can differentiate into the correct cell type, and form natural connections with the surrounding tissue, which is very important in neurodegenerative diseases such as Parkinson’s and Alzheimer’s.

Stem cells may also be useful in tissue-engineering applications, such as the production of complete organs, including heart, liver, kidneys, eyes or even parts of the brain.

Stem cells represent a potentially unlimited source of experimental tissue, which would permit research into other areas. For example, researchers could test stem cells derived from culture in the laboratory for the effects of known environmental hazards and genetic mutations on the relevant human tissue. This would provide more applicable information than that obtained in animal models.

　

　

Stem Cell Transplant

A stem cell transplant is used to increase the chance of a cure or remission for a number of cancers and blood disorders. It usually involves intense chemotherapy followed by an infusion of stem cells. The treatment requires close nursing and medical care for a number of weeks. It can be a gruelling treatment and there are risks. Your specialist can advise when the likely benefits of this procedure can outweigh the risks.

What is a stem cell transplant?

A stem cell transplant may be used so that you can have intensive high dose chemotherapy (and sometimes radiotherapy) to kill cancerous cells. The chemotherapy is higher than conventional chemotherapy and also kills the stem cells in the bone marrow that would normally make blood cells. Therefore, following the chemotherapy, you are given back (transplanted) stem cells which can then make normal blood cells again.

A stem cell transplant is sometimes called a bone marrow transplant. However, stem cells can be obtained from blood as well as from the bone marrow. So, the term stem cell transplant is now used.

What is the bone marrow, and what are stem cells and blood cells?

Bone marrow

Blood cells are made in the bone marrow by stem cells. Bone marrow is the soft ’spongy’ material in the centre of bones. Large flat bones such as the breast-bone (sternum) and pelvis contain the most bone marrow. To constantly make blood cells you need a healthy bone marrow. You also need nutrients from your diet including iron and some vitamins.

Stem cells

Stem cells are primitive (immature) cells. There are two main types in the bone marrow – myeloid and lymphoid stem cells. These derive from even more primitive common ‘pluripotent’ stem cells. Stem cells constantly divide and produce new cells. Some new cells remain as stem cells and others go through a series of maturing stages (‘precursor’ or ‘blast’ cells) before forming into mature blood cells.

Blood cells

Mature (fully formed) blood cells are released from the bone marrow into the bloodstream. Mature blood cells are:

• Red cells (erythrocytes). These make blood a red colour. One drop of blood contains about five million red cells. Red cells contain a chemical called haemoglobin. This binds to oxygen, and takes oxygen from the lungs to all parts of the body.
• White cells (leucocytes). The different types of white cells are called neutrophils (polymorphs), lymphocytes, eosinophils, monocytes, and basophils. They are part of the immune system. Their main role is to defend the body against infection.
• Platelets. These are tiny and help the blood to clot if we cut ourselves.

Stem cells rapidly multiply to make millions of blood cells each day. Because of this they are more easily killed by chemotherapy than most other cells in the body. This is because chemotherapy drugs work by killing rapidly dividing cells (such as cancer cells).

When is a stem cell transplant used for treatment?

A stem cell transplant is an option which is considered for various cancer conditions. For example, for types of leukaemia, lymphoma and myeloma. Your specialist will advise when it may be an appropriate option. As a rule, it is not often a ‘first line’ treatment. Conventional chemotherapy or other treatments tend to be used first. However, the treatment of cancer and leukaemia is a changing and developing area of medicine. Techniques such as stem cell transplant continue to be refined and improved and may be considered in various different circumstances.

The higher doses of chemotherapy and radiotherapy that can be used in conjunction with a stem cell transplant can improve the chance of a cure for some conditions in certain circumstances.

A stem cell transplant is also used for some rare non-cancerous blood disorders.

Where are stem cells obtained from?

An autologous transplant

This means that the stem cells used for the transplant come from your own body. They are usually collected when you are free of any sign of disease (when you are ‘in remission’) following conventional chemotherapy or other treatments. The stem cells can be used soon after being collected. They can also be frozen, stored and used in the future if needed.

An autologous stem cell transplant is also called ’stem cell support’ as the stem cells come from your own body. So, strictly speaking, it is not a transplant from a donor.

An allogenic transplant

This means the stem cells used for the transplant come from someone else – a donor. This is often a close relative such as a brother or sister where there is a good chance of a close ‘match’. Unrelated donors are sometimes matched to people needing a transplant.

Stem cells can be collected:

• From the bone marrow. This involves a small operation to collect some marrow from the pelvic bone.
• From the blood. Some stem cells occur in the blood (most are in the bone marrow). The stem cells in the blood can be collected (‘harvested’) by a machine called a cell separator. The bloodflow is diverted from a vein in the arm to pass through the machine which separates out the stem cells. The procedure takes about 4-6 hours. Drugs are given for a few days before this procedure to stimulate the body to make more stem cells in the bone marrow which ’spill out’ into the blood.

How is a stem cell transplant given?

It is very similar to a blood transfusion. Following the intense course of chemotherapy (and sometimes radiotherapy), the solution containing stem cells is given into one of your veins via a drip. The stem cells travel through your bloodstream and end up your bone marrow. Here they start to make blood cells.

It can take several weeks for your bone marrow to recover, to take up the transplanted stem cells, and to make enough new blood cells. During this time you will need to be in hospital and be closely monitored. You may need several blood transfusions during this time until you are making enough blood cells. Antibiotics are given to minimise the risk of infection. Also, drugs are given to help stimulate the stem cells to multiply as quickly as possible.

What are the main risks of having a stem cell transplant?

There is a risk of serious problems with a stem cell transplant. For example:

• Infection is the main risk. Following the intense chemotherapy, and before the time your bone marrow is working again, you have very low immunity. During this time you are at risk of serious and life-threatening infections. This is why antibiotics are given and you will be nursed away from other people until your bone marrow recovers. This can take several weeks.
• Bleeding problems from the low level of platelets after the chemotherapy.
• It you have a transplant from a donor, there is some risk that the ‘match’ will not be perfect, and the donor cells may react with your body’s cells. This is called ‘graft versus host disease’. This is not always serious but sometimes it can be.
• Rarely, the transplanted stem cells fail to work.
• There is a risk of short-term and long-term side-effects from intense chemotherapy (and/or radiotherapy).

Your specialist will discuss the risks and possible side-effects involved with a stem cell transplant.

 

 

 

High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) Study

 

This study is currently recruiting participants.

 

Verified by National Institute of Allergy and Infectious Diseases (NIAID), January 2009

First Received: February 7, 2006   Last Updated: March 3, 2009  

 

History of Changes

Sponsors and Collaborators:

National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network

Information provided by:

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT00288626

Purpose

The purpose of this study is to determine the effectiveness of a new treatment for multiple sclerosis (MS), a serious disease in which the immune system attacks the brain and spinal cord. MS can be progressive and severe and lead to significant disability. The study treatment involves the use of high-dose chemotherapeutic drugs to suppress the immune system. The participant’s own (autologous) blood-forming (hematopoietic, CD34+) stem cells are collected before the chemotherapy is given, and then transplanted back into the body following treatment. Transplantation of autologous hematopoietic stem cells is required to prevent very prolonged periods of low blood cell counts after the high-dose chemotherapy.

 

Condition

Intervention

Phase

 

 

Multiple Sclerosis

 

Drug: Granulocyte-colony stimulating factor (G-CSF) and prednisone
Drug: Carmustine, etoposide, cytarabine, and melphalan (BEAM)
Procedure: Autologous hematopoietic stem cell transplant

 

Phase II

 

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Prednisone Cytarabine hydrochloride Etoposide Etoposide phosphate Granulocyte colony-stimulating factor Cytarabine Melphalan Carmustine Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

 

 

Study Type:

Interventional

 

Study Design:

Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

 

Official Title:

A Phase II Study of High-Dose Immunosuppressive Therapy (HDIT) Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) and Thymoglobulin, and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) for the Treatment of Poor Prognosis Multiple Sclerosis

 

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

 

 

Primary Outcome Measures:

 

·      Time to treatment failure [ Time Frame: During the 5 years after transplant ] [ Designated as safety issue: No ]

 

Estimated Enrollment:

30

 

Study Start Date:

July 2006, still recruiting

 

Estimated Study Completion Date:

January 2015

 

Estimated Primary Completion Date:

September 2014 (Final data collection date for primary outcome measure)

 

 

Arms

 

Assigned Interventions

 

1: Experimental

 

Drug: Granulocyte-colony stimulating factor (G-CSF) and prednisone

Growth factor regimen; occurs at study entry

Drug: Carmustine, etoposide, cytarabine, and melphalan (BEAM)

High-dose chemotherapy; occurs seven or more days following collection of autologous graft

Procedure: Autologous hematopoietic stem cell transplant

Occurs after growth factor regimen and collection of autologous graft

 

Detailed Description:

MS is a chronic autoimmune disease of the central nervous system in which myelin, the protective coat that surrounds nerve cells, is damaged or destroyed by autoimmune T cells and macrophages, leading to an eventual loss of neurologic function. In a pilot study in Europe using high-dose chemotherapy, it was observed that 18 of 19 MS patients stabilized or improved clinically, and only one patient showed a new lesion on magnetic resonance imaging (MRI) of the brain at 4.5 years after treatment. Improvement was seen in quality-of-life assessments.

In ITN033AI, high-dose chemotherapy with autologous CD34-selected hematopoietic cell transplantation will be given to confirm the results from the pilot study and to offer therapy to patients with early MS and a poor prognosis. Research studies will be performed in addition to clinical assessments to better understand the effect of the treatment on the activity of MS. High-dose chemotherapy will be used to deplete autoreactive immune cells. These regimens also deplete the bone marrow, the source of blood-forming CD34+ stem cells which causes very low blood counts. Therefore, the participant’s autologous CD34+ hematopoietic stem cells will be collected before high dose immunosuppressive therapy is given and then returned as a transplant post-chemotherapy. Patients will be followed closely after the autologous transplantation since they will be at risk for infections after treatment.

At the beginning of the study, participants will undergo a number of screening and baseline procedures, including a physical exam, blood collection, MS-confirming neurology exams and questionnaires, and MRI procedures. Participants will be given prednisone and granulocyte-colony stimulating factor (G-CSF) to mobilize CD34+ hematopoietic stem cells from the bone marrow into the peripheral blood. When the peripheral blood CD34+ cell count reaches 20,000 cells/ml or greater, these cells will be collected by leukapheresis. In this process, a catheter is placed into a large blood vessel, peripheral blood is withdrawn, and a high speed sedimentation (leukapheresis) device is used to separate and retain the cells required for autologous transplantation. Other blood cells are then returned to the participant’s body. In the laboratory, the CD34+ hematopoietic stem cell graft will be selected and prepared from the leukapheresis collection, and stored until needed for transplant. Seven or more days following the collection of their autologous graft, participants will be hospitalized and receive high-dose chemotherapy consisting of carmustine, etoposide, cytarabine, and melphalan (BEAM) and thymoglobulin. This is followed by transplantation of the autologous hematopoietic cell graft. Participants will remain in the hospital for observation during recovery of their peripheral blood cell counts, as described in the protocol. Participants will receive G-CSF and blood transfusions, if needed, and will be monitored for infections. Following discharge from the hospital, eight study visits will occur over sixty months (five years).

During these visits, participants will undergo blood and urine collection, MRI studies, leukapheresis, and MS neurology exams and will complete questionnaires.

 

 

Eligibility

 

Ages Eligible for Study:  

 

18 Years to 60 Years

 

Genders Eligible for Study:

  

Both

 

Accepts Healthy Volunteers:

 

No

Criteria

Inclusion Criteria:

·      Diagnosis of relapsing-remitting or progressive-relapsing multiple sclerosis for less than 15 years using McDonald Criteria. More information on this criterion can be found in the protocol.

·      Score between 3.0 and 5.5 on the Expanded Disability Status Scale (EDSS)

·      T2 abnormalities on brain MRI consistent with MS

·      Two or more relapses in 18 months time on interferon (IFN), glatiramer acetate (GA), natalizumab or cytotoxic therapy with EDSS increase of 1.0 or greater for participants with EDSS at screening of 3.0 to 3.5 (0.5 or greater for participants with EDSS at screening of 4.0 to 5.5) sustained at least 4 weeks after at least one of these relapses OR one relapse on IFN, GA, natalizumab or cytotoxic therapy with EDSS increase of 1.5 or greater (1.0 for subjects with EDSS at screening of 5.5) sustained at least 4 weeks, together with MRI changes consistent with poor prognosis. More information on this criterion can be found in the protocol.

·      On IFN or GA for at least 6 months before the relapses occur that are counted to satisfy previous inclusion criterion OR have received adequate doses of natalizumab or cytotoxic therapy on a treatment schedule before the relapses occur that are counted to satisfy previous inclusion criterion.

·      Approval by an MS Review Panel to participate in the study. More information on this criterion can be found in the protocol.

·      In good clinical condition with adequate organ function and without coexisting medical problems that would increase the risk to the participant

·      Willing to use acceptable methods of contraception

·      Willing and able to comply with all study requirements

·      Willing to accept and comprehend irreversible sterility as side effect of therapy

Exclusion Criteria:

·      Primary progressive MS

·      Secondary progressive MS without relapses (i.e., progression without exacerbations or relapses) for 12 or more months

·      Neuromyelitis optica, a disease similar to MS

·      Initiation of new immunosuppressant treatment after the participant becomes eligible for the protocol or continuance of immunosuppressant drugs after the participant is screened for the protocol. Treatment with IFN, GA, or corticosteroids is permitted after the participant becomes eligible for the protocol.

·      Lapse of greater than 6 months between the time a participant is eligible for the protocol and initiation of protocol treatment except when judged acceptable by the MS Review Panel

·      Prior treatment with investigational immunosuppressive agents within 3 months of study eligibility

·      Positive baseline plasma and CSF testing for JC virus or a brain MRI that has changes consistent with a diagnosis of progressive multifocal encephalopathy (PML).

·      History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS)

·      Active hepatitis B or C infection, cirrhosis, or HIV infection

·      Uncontrolled diabetes mellitus

·      Uncontrolled viral, fungal, or bacterial infection. Patients with asymptomatic bacteriuria are not excluded.

·      Any illness that would jeopardize the ability to tolerate aggressive chemotherapy

·      Prior history of malignancy, except localized basal cell or squamous skin cancer. Other malignancies for which the subject is judged cured by the administered therapy will be considered on an individual basis.

·      Hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins or to iron compounds/medications

·      Metallic objects implanted in the body that would affect MRI exams

·      Psychiatric illness, mental deficiency, or cognitive dysfunction

·      Pregnancy

·       

Contacts and Locations

 

Please refer to this study by its ClinicalTrials.gov identifier: NCT00288626

Locations

 

United States, Ohio

Ohio State University School of Medicine

 

Recruiting

 

Columbus, Ohio, United States, 43210

Contact: Lisa Hafer     614-293-7877     hafer.15@osu.edu    

Principal Investigator: Michael K. Racke, MD            

Principal Investigator: Steven M. Devine, MD            

 

United States, Texas

 

M.D. Anderson Cancer Center; Transplant site, please contact Baylor College of Medicine

 

Recruiting

 

Houston, Texas, United States, 77230-1402

Contact: Uday Popat, MD     713-745-3055     upopat@mdanderson.org    

Principal Investigator: Uday Popat, MD            

Baylor College of Medicine

Recruiting

Houston, Texas, United States, 77030

Contact: Semahat Eiswirth, RN     713-798-6059     sparilti@bcm.edu    

Contact: George J. Hutton, MD     713-798-8170     ghutton@bcm.tmc.edu    

Principal Investigator: George J. Hutton, MD            

United States, Washington

Fred Hutchinson Cancer Research Center

 

Recruiting

 

Seattle, Washington, United States, 98109-1024

Contact: Bernie McLaughlin, RN     206-667-4916     bmclaugh@fhcrc.org    

Principal Investigator: James Bowen, MD            

Principal Investigator: Richard Nash, MD            

Principal Investigator: George H. Kraft, MD

 

           

Sponsors and Collaborators

 

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network

 

Investigators

 

Study Chair:

Richard A. Nash, MD

Fred Hutchinson Cancer Research Center, Clinical Research Division, University of Washington

Study Chair:

James D. Bowen, MD

Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, Washington

Study Chair:

George H. Kraft, MD

Departments of Neurology and Rehabilitation Medicine, University of Washington

Study Chair:

George J. Hutton, MD

The Maxine Messinger Multiple Sclerosis Clinic, The Methodist Hospital, Baylor College of Medicine

Study Chair:

Uday Popat, MD

Department of Blood and Marrow Transplantation, University of Texas, M.D. Anderson Cancer Center

Study Chair:

Michael K. Racke, MD

Department of Neurology, Ohio State University Medical Center

Study Chair:

Steven M. Devine, MD

Department of Hematology and Oncology, Ohio State University Medical Center

 

 

More Information

Additional Information:

Click here for the Immune Tolerance Network Web site 

Publications:

Fassas A, Nash R. Stem cell transplantation for autoimmune disorders. Multiple sclerosis. Best Pract Res Clin Haematol. 2004 Jun;17(2):247-62. Review.

Muraro PA, Douek DC. Renewing the T cell repertoire to arrest autoimmune aggression. Trends Immunol. 2006 Jan 4; [Epub ahead of print]

Muraro PA, Douek DC, Packer A, Chung K, Guenaga FJ, Cassiani-Ingoni R, Campbell C, Memon S, Nagle JW, Hakim FT, Gress RE, McFarland HF, Burt RK, Martin R. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med. 2005 Mar 7;201(5):805-16. Epub 2005 Feb 28.

Saccardi R, Mancardi GL, Solari A, Bosi A, Bruzzi P, Di Bartolomeo P, Donelli A, Filippi M, Guerrasio A, Gualandi F, La Nasa G, Murialdo A, Pagliai F, Papineschi F, Scappini B, Marmont AM. Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood. 2005 Mar 15;105(6):2601-7. Epub 2004 Nov 16.

Tyndall A, Saccardi R. Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: results from phase I/II studies, prospective randomized trials and future directions. Clin Exp Immunol. 2005 Jul;141(1):1-9. Review.

Mancardi G, Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol. 2008 Jul;7(7):626-36. Review.

 

Responsible Party:

DAIT/NIAID ( Associate Director, Clinical Research Program )

Study ID Numbers:

DAIT ITN033AI, DAIT SCMS2

Study First Received:

February 7, 2006

Last Updated:

March 3, 2009

ClinicalTrials.gov Identifier:

NCT00288626     History of Changes

Health Authority:

United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Hematopoietic Stem Cell Transplantation
Immunosuppressive Agents

Study placed in the following topic categories:

Antimetabolites
Prednisone
Melphalan
Autoimmune Diseases
Demyelinating Diseases
Carmustine
Sclerosis
Antiviral Agents
Immunosuppressive Agents
Etoposide phosphate

Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Mitogens
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Alkylating Agents
Etoposide
Autoimmune Diseases of the Nervous System
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Melphalan
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Pathologic Processes
Multiple Sclerosis
Therapeutic Uses
Etoposide
Alkylating Agents
Cytarabine

Autoimmune Diseases of the Nervous System
Autoimmune Diseases
Immune System Diseases
Demyelinating Diseases
Carmustine
Nervous System Diseases
Sclerosis
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Myeloablative Agonists
Demyelinating Autoimmune Diseases, CNS
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 06, 2009

 

Tysabri & PML In MS Patients

 

Helen Yates, Chief Executive of the Multiple Sclerosis Resource Centre (MSRC) said: “We truly hope that the research leads to a treatment for this very worrying and potentially life threatening condition. It is important that people affected by MS that are undergoing treatment with Tysabri have as much reassurance as possible about the potential side effects and the ability to treat them should they arise.” As reported by The Irish Times: A possible treatment for a potentially fatal side effect of multiple sclerosis therapy, Tysabri, and other immune-modulating drugs is currently under investigation. Biogen Idec, Elan’s partner in the development and sale of Tysabri, is testing the efficacy of a malaria pill developed during the Vietnam war in treating progressive multifocal leukoencephalopathy (PML), the brain infection that has been tied to use of Tysabri, according to Al Sandrock, Biogen’s head of neurology research. Tysabri was pulled from the market in 2005 after three PML cases were reported. It was reintroduced in 2006 when US regulators said the medication’s effectiveness, twice that of other MS drugs, outweighed its risks. However, the threat of PML has affected sales of the treatment which, although a successful drug in commercial terms, is well short of the figures initially expected. The companies have reported five new PML cases since July 2008, reigniting concerns of patients who believe a safer Tysabri would be their best treatment option, said John Richert of the US National Multiple Sclerosis Society. Tysabri, a laboratory-engineered antibody, is designed to suppress the immune attack that leads to MS. PML occurs when a common germ, called JC virus, mutates, evades the body’s immune defences and penetrates the brain, causing irreversible damage. Biogen has been seeking a PML treatment since 2005, screening about 2,000 compounds known to fight brain infections. The drug showing the most promise in laboratory tests was the commonly used malaria pill, mefloquine. A clinical trial is now testing mefloquine in 40 patients with PML from any cause, whether drug-related or from HIV. The goal is to see whether mefloquine, sold by Roche Holding under the name Lariam, can treat PML when it occurs. The trial is expected to be completed by the end of the year. Source Multiple Sclerosis Resource Centre Main News Category: Multiple Sclerosis Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions. 29 Mar 2009

Dear Readers,

 

 

 

I would like to explain to you why I haven’t posted very many articles on my blog for the past few months.

 

 

 

I had a relapse in October 2008 and just could not seem to get my sluggish brain to do any research with any amount of understanding.  Then came Christmas and all the hubbub over that.  Our family has decided to make our Christmas presents from now on, and only buy for the little guy in our life.  Making presents sounds like a great idea; no commercialism, no great expenditure, creative, etc.  But, as I didn’t start to make my presents early enough (mostly because I couldn’t think of what to make for everyone) I was up to the wire in finishing my creations.  I vowed that I would start sewing for everyone earlier this year.  Ha, I haven’t started yet for this year.

 

 

 

Shortly after Christmas I slipped into a depression.  Depression has always been a struggle for me since I am bi-polar (manic depressive).  Shortly after I swam up from the depths of depression, my husband was hospitalized with a very severe form of pneumonia.  He was hospitalized for a little over a week.  When he went for his check-up, after that episode.  His doctor noticed that his leg was swollen, red, and hot.  Of course, he was sent for x-rays and an ultra sound.  The radiologist appeared in the room and said that he had blood clots from his groin to his ankle.  My husband was duly sent to the emergency at our local hospital.  After many hours in that place he was admitted and put on warfarin.  The specialist said that his pneumonia was caused by a clot breaking away and settling in his lung.  He could have died.  He has not be able to work since he was in with pneumonia and will not be able to work for another 3 months, that will be 6 months in total.  His leg is still quite red and swollen.

 

 

 

After my husband’s illness sort of settled down, my daughter became ill.  She has had to get monthly blood work done for several months because of some medication she is taking.  Her doctor commented on the fact that her white blood count was up and down, sometimes being very high.  Other blood counts were out off kilter and never the same twice.  That doctor did not seem all that concerned about these inconsistencies in her blood.  Not long after she started going to a different doctor he became very concerned about these inconsistencies.  He has referred her to various specialists.

 

 

 

My daughter has been without energy and sleeps more than is normal for months now.  She is always cold most of the time and is really only comfortable when the house is around 30 Celsius or 90 Fahrenheit.  I, of course, can’t bare the temperature being that high.

 

 

 

About a month ago she informed me that she hadn’t urinated all day and was in a great deal of pain.  Of course, I had to drive her the 40 miles to the emergency.  My husband could not come because he still couldn’t walk at this stage.  An ultrasound showed that she had two kidney stones that were small enough to pass.  They prescribed antibiotics and dilaudin for the pain.  She seemed to pass these stones a few days later.

 

 

 

But, that did not account for the strange blood work and pain in her lower back.  To date she has seen an urologist, an internist, and a nephrologist.  We are now awaiting the results of the many tests that have been preformed on her urine, blood, and body. 

 

 

 

I am so happy that Canada has Medicare.  We have not had to pay for any of the doctors or procedures.  Both my daughter and my husband were able to be admitted to the ER and see their respective specialists without delay.  Within 3 weeks of being in the emergency department  my daughter saw all the specialists and had all the tests preformed, without waiting and without charges.

 

 

 

Needless to say, this has been a very hectic time for our family.  My brain is only just now starting to be able to guide me in my research and interpretations of the research that I must do for this blog.  I always transform my research into layman’s terms so you, my readers, can understand it.

 

 

 

 

 

Bonnie

 

 

 

Emergency, Medicare, pain, blood clot, white blood count,

 

 

 

 

 

 

 

 

 

 

 

 

Multiple Sclerosis Impact Scale (MSIS-29)

 

 

• The following questions ask for your views about the impact of MS on your day-to-day life during the past two weeks

 

• For each statement, please circle the one number that best describes your situation

 

• Please answer all questions

 

 

The following may not appear on your screen completely.  I am unable to change the font size in WordPress.  Therefore I will tell what each of the columns are:

 

1. Not at all       
2. A little  
3. Moderately               
4. Quite a bit     
5. Extremely

 

In the past two weeks, how much has your MS limited your ability to… Not at all A little Moderately Quite a bit Extremely   1. Do physically demanding tasks?   1 2 3 4 5 2. Grip things tightly (e.g. turning on taps)? 1 2 3 4 5 3. Carry things?   1 2 3 4 5

 

In the past two weeks, how much have you been bothered by… Not at all A little Moderately Quite a bit Extremely   4. Problems with your balance?   1 2 3 4 5 5. Difficulties moving about indoors? 1 2 3 4 5 6. Being clumsy?   1 2 3 4 5 7. Stiffness?   1 2 3 4 5 8. Heavy arms and/or legs?   1 2 3 4 5 9. Tremor of your arms or legs?   1 2 3 4 5 10. Spasms in your limbs?   1 2 3 4 5 11. Your body not doing what you want it to do? 1 2 3 4 5 12. Having to depend on others to do things for you? 1 2 3 4 5   Please check that you have answered all the questions before going on to the next page

 

 

 

 

In the past two weeks, how much have you been bothered by… Not at all A little Moderately Quite a bit Extremely   13. Limitations in your social and leisure activities at home? 1 2 3 4 5 14. Being stuck at home more than you would like to be? 1 2 3 4 5 15. Difficulties using your hands in everyday tasks? 1 2 3 4 5 16. Having to cut down the amount of time you spent on work or other daily activities? 1 2 3 4 5 17. Problems using transport (e.g. car, bus, train, taxi, etc.)? 1 2 3 4 5 18. Taking longer to do things?   1 2 3 4 5 19. Difficulty doing things spontaneously (e.g. going out on the spur of the moment)? 1 2 3 4 5 20. Needing to go to the toilet urgently? 1 2 3 4 5 21. Feeling unwell?   1 2 3 4 5 22. Problems sleeping?   1 2 3 4 5 23. Feeling mentally fatigued?   1 2 3 4 5 24. Worries related to your MS?   1 2 3 4 5 25. Feeling anxious or tense?   1 2 3 4 5 26. Feeling irritable, impatient, or short tempered? 1 2 3 4 5 27. Problems concentrating?   1 2 3 4 5 28 Lack of confidence?   1 2 3 4 5 29. Feeling depressed?   1 2 3 4 5   Please check that you have circled ONE number for EACH question