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Transplantation for multiple sclerosis

Aleksandr S. Fedulov, MD, Professor

Chief of the Department of Nerve and Neurosurgical Disorders of Belarusian State Medical University

Phone: +375172-72-55-97

Fax: +375172-72-41-63

Email: Адрес электронной почты защищен от спам-ботов. Для просмотра адреса в вашем браузере должен быть включен Javascript.

 

What is multiple sclerosis (MS)?

Nerve cells, neurons, have the processes, which transmit nerve impulses. The processes are covered with insulating substance myelin, which serves the same way as the insulation of an electrical cable and ensures a proper speed of impulse transmission.

Signs, symptoms and causes of multiple sclerosis

The cause of multiple sclerosis is still unknown. There are numerous theories about the causes of its development. Some researchers believe it is caused by genetic abnormalities, others think it is caused by viruses.

Today, multiple sclerosis is considered to be an autoimmune disorder. It means that the self-antibodies, which usually protect the human body from infections, become aggressive to self-tissues and start damage normal cells.

Multiple sclerosis damages the cells, which produce myelin. Myelin insulates nerve fibers. That is why multiple sclerosis is considered to be a demyelinating disease. MS interrupts the transmission of nerve impulses along nerve fibers, causing various neurological disorders.

In general, MS is a multifactor disease, i.e. it is caused by a bulk of factors.

MS usually affects people aged 18-50. If not properly treated, MS causes significant neurological problems, for instance, leg and arm weakness, sensation disorders, vertigo, problems with vision, speech, swallowing, dysfunction of pelvic organs, psychoneurological dysfunction. MS may even lead to problems with self-care.

Therefore, MS is one of the most common reasons of inability to work and disability among young people.

MS manifests itself in many different ways. The signs and symptoms of the disease vary from patient to patient, and may be different even in one patient. MS may cause the so-called “blind” foci of demyelination. Such foci can only be detected with the help of special tests. However, there are no 100% reliable tests to confirm the disease.

The disease is characterized by a constant progress and increase of neurological deficiency and reduction of stabilization time. Less than 1/3 of patients remain socially active 15 years after being diagnosed with MS.

Unfortunately, the disease is still incurable. However, MS is not a verdict.

The key goal of treatment is to stabilize a patient and prevent recurrence of the disease.

During acute attacks of the disease, a physician usually prescribes corticosteroid therapy (hormonal therapy). The therapy suppresses the aggressive attacks of the immune system to self-cells (self-aggression).

Plasmapheresis is also widely used to temper the disease. During plasmapheresis autoantibodies are removed from blood (blood becomes “clear”).

Thus, hormonal therapy and plasmapheresis are the main (basic) therapies for MS.

Foreign physicians use interferon and glatiramer acetate to treat the patients with MS. Such treatment is very expensive. The cost of annual treatment varies from $ 15.000 TO $ 18.000. Besides, from 50% to 60% of the patients are resistant to therapy.

Today, many physicians apply the new type of treatment ‑ high-dose polychemotherapy followed by hematopoietic stem cell transplantation.

What are stem cells? Stem cells are undifferentiated cells of the human body, which may differentiate into any other types of cells.

Hematopoietic stem cells are the stem cells, which may form various blood cells. Normally, the red bone marrow contains small amount of hematopoietic stem cells. The red bone marrow is located in pelvic bones, chest bone, vertebrae, etc.

It is important to mention, that during treatment we use only autologous stem cells, i.e. the stem cells obtained from the patients themselves. Since patients’ stem cells do not contact with the environment during the whole treatment, the procedure of stem cell injection is absolutely safe.

High-dose polychemotherapy destroys aggressive antibodies (autoantibodies). In combination with stem cell transplantation, it helps to reset the functions of the immune system, to stabilize the patients with MS and to reduce recurrence rate. This is the key goal of therapy.

About 2000 patients have received high-dose polychemotherapy combined with stem cell transplantation since 1997. According to clinical trials, such approach helps to completely stop the progress of the disease in most cases.

According to the information available, hematopoietic stem cells may be transferred to the central nervous system and transform into nerve cells there.

It should be mentioned, that received high-dose polychemotherapy combined with stem cell transplantation is more effective in young patients, who have progressive MS of early stages.

The approach is not safe. It may cause complications during an early and late post-transplantation period, i.e. significant changes in blood composition, nausea, vomiting, esophagitis, gastroduodenitis, diarrhea, skin lesions, hair loss, infections, reproductive and thyroid disorders, problems with eyes. 1-1.5% of fatal cases were reported.

Before starting such treatment, we thoroughly examine patients with a view to detecting occult diseases and preventing complication.

Indications for treatment:

  • MS confirmed by the results of magnetic resonance imaging with > 1 deterioration of neurological status over the last year (according to EDSS scale). EDSS is an expended disability status scale, which is used to assess the degree of neurological dysfunction;
  • failure of a previous combined therapy;
  • age 18 – 45;
  • normal age-gender-predicted rates according to laboratory tests;
  • ability to self-service and move without help;
  • strong motivation.

Contraindications for treatment:

  • pregnancy;
  • lactation;
  • sever concomitant diseases (congestive cardiac failure, unstable angina, disturbance of rhythm and conduction, myocardial infarction, pneumonia, heart failure, kidney failure, sepsis, bleeding, mental disorders, decompensated diabetes mellitus, physical disability, cachexia);
  • significant deviation of age-gender-predicted rates shown by the results of laboratory tests;
  • life-threatening bleeding (gastrointestinal bleeding, uterine bleeding, brain bleeding);
  • severe mental disorders (delusion, depression);
  • concomitant cancer;
  • acute or active chronic inflammation in paranasal sinuses;
  • acute or active chronic inflammation in the oral cavity.

Stem cell transplantation procedure

Stage 1. First, a patient undergoes neurological, hematological and general testing. Then, the risk-benefit ratio is quantified. If the risk of the treatment is lower than benefit from it, the patient may be included into the project.

Stage 2. If a patient is included into the project, the patient signs an informed consent for the receipt of a high-dose polychemotherapy followed by hematopoietic stem cell transplantation.

Patients undergo the above tests and procedures at Department of Neurology No.2 of the 9th City Clinical Hospital and at the Republican Research and Practice Center for Neurology and Neurosurgery. At stage 1-2, patients also receive leikladin (domestic immunosuppressive drug).

Stage 3. Location: the Republican Center of Transplantation and Cell Biotechnology. A patient’s venous blood is collected into a separator. A separator is used to separate stem cells from other blood cells. The number of stem cells in the peripheral blood is low. To collect a required amount of stem cells, a physician uses special agents to mobilize them. The collected stem cells are frozen and stored in liquid nitrogen. They may be stored for a long period of time.

Stage 4. The key objective of the 4th stage is to kill “ill” immune cells, which destroy the tissue of the central nervous system. It is a hard job, because “ill” cells are located not only in brain and bone marrow, but almost in all tissues of a patient’s body. To achieve the objective, a physician injects a patient with highly effective immunosuppressive and anti-inflammatory medications. The medications kill all “ill” immune cells.

Stage 5. After that, a patient receives intravenous injections of a patient’s own stem cells, which were collected and frozen earlier. The stem cells are thawed immediately before the transplantation. After being injected, the stem cells solve two problems, i.e. they restore the immune system so that it may protect a patient’s body and to restore the hematopoiesis.

We follow up the patients after transplantation, so that to ensure engraftment of stem cells and to prevent infections. Patients stay in a special sterile ward equipped with an air and water treatment system until restoration of their immune system.

We thoroughly select the patients for transplantation and prescribe them special therapies after transplantation with a view to preventing complications.

We have been applying a combination of polychemotherapy and stem cell transplantation for 4 years. The data of own research, conducted in 2004-2008, proved the data obtained during the research within the international program for the use of hematopoietic peripheral blood stem cell transplantation in treatment of MS. The program was headed by the European Bone Marrow Transplant Group( EBMTG). The obtained data showed that the patients, who received such therapy, stabilized.

If you want to participate in the project, please, send us the filled out registration form at Адрес электронной почты защищен от спам-ботов. Для просмотра адреса в вашем браузере должен быть включен Javascript..

If you meet the selection criteria (see Indications above), we will place you on the waiting list.

A.S. Fedulov, MD, Professor, Chief of the Department of Nerve and Neurosurgical Disorders of Belarusian State Medical University, is the lead of the research team.

Contacts:

Phone: +375172-72-55-97

Fax: +375172-72-41-63

Email: Адрес электронной почты защищен от спам-ботов. Для просмотра адреса в вашем браузере должен быть включен Javascript.

Team Staff:

  • A.V. Borisov, PhD in Medicine, Chief of the Laboratory of Clinical and Experimental Neurology and Neurosurgery of the Central Research Laboratory of Belarusian State Medical University;
  • A.L. Uss, MD, Porfessor, Chief of the Republican Center of Transplantation and Cell Biotechnology, Chief of the Department of Clinical Hematology and Blood Transfusion of Belarusian Medical Academy of Post Graduate Education, Deputy Chief Physician of the 9th City Clinical Hospital;
  • V.A. Zmachinsky, MD, Chief Freelance Hematologist of the Ministry of Health of the Republic of Belarus, Associate Professor of the Department of Hematology and Blood Transfusion of Belarusian Medical Academy of Post Graduate Education;
  • N.F. Milanovich, PhD in Medicine, Chief of the Department of Bone Marrow Transplantation of the 9th City Clinical Hospital;
  • P.B. Mitskevich, PhD in Medicine, Chief of the Clinical Laboratory of the Republican Center of Transplantation and Cell Biotechnology;
  • A.G. Baida, resident physician of Department of Neurology No.2 of the 9th City Clinical Hospital;
  • N.D. Volkovets, physician of the Department of Bone Marrow Transplantation of the 9th City Clinical Hospital;
  • E.V. Dzyuba, physician of the Department of Bone Marrow Transplantation of the 9th City Clinical Hospital;
  • M.M. Morozova, physician of the Department of Bone Marrow Transplantation of the 9th City Clinical Hospital;
  • V.V. Smolnikov, laboratory technician of the Clinical Laboratory of the Republican Center of Transplantation and Cell Biotechnology;
  • N.S. Solovieva, 1st category Software Engineer of the Republican Center of Transplantation and Cell Biotechnology;
  • M.F. Minzer, resident physician of the Department of Function Testing of Minsk Consulting and Diagnostic Center;
  • E.E. Chernysh, resident physician of the Department of Function Testing of Minsk Consulting and Diagnostic Center;
  • I.V. Bulaev, X-Ray technician of the Department of Radiology of the Republican Research and Practice Center of Trauma and Orthopedics;
  • I.V. Pyko, Neurosurgeon, candidate and junior researcher of the Laboratory of Clinical and Experimental Neurology and Neurosurgery of the Central Research Laboratory of Belarusian State Medical University;
  • Y.M. Motuzova, Neurologist, postgraduate student of the Department of Nerve and Neurosurgical Disorders of Belarusian State Medical University.
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