Treatment for multiple sclerosis and immune disorders

Treatment for multiple sclerosis and immune disorders

The treatment of multiple sclerosis and immune disorders can be divided in either corticosteroids and plasmapheresis (plasma exchange) to control attacks or a treatment that modifies the course of the disease and prevents new attacks. There are many preventive meds today among which are immunosuppressive drugs and immunomodulators.

Drugs that suppress the immune system have been used for almost 50 years. In the case of multiple sclerosis, interferons are the main therapy in recent years. In many cases, however, the disease remains active: ten years after onset 50% of the patients are chronically and progressively worse; 15 years after onset 70%, and 25 years afterwards 85%.

What is ASCT - autologous stem cell transplantation?
ASCT is a radical immunosuppressive procedure being performed in several clinics in Brazil. In this kind of transplant the patient undergoes a series of procedures beginning with cyclophosphamide (an immunosuppressant medication widely used to treat multiple sclerosis and other immune disorders). After that, stem cells are collected and, after a period of rest, a massive chemotherapy takes place so as to eliminate the bone marrow that is then remade with the stem cells. In 44 multiple sclerosis cases treated in Brazil, 9 deceased. (Globe Reporter, January 2005).

In a recent lecture in Brazil, professor Athanasios Fassas, member of the European Bone Marrow and Stem Cell Transplantation Group, reported that in 210 patients with multiple sclerosis treated with ASCT until 2003, the mortality rate was 8% and severe morbidity 59%. Severe morbidity means to have to stay in the hospital in a high level of suffering. More than 50% of the survivors reach long lasting remissions. The ideal patient to be submitted to ASCT must be in good general health, has mild to moderate disability and a high risk of rapid and irreversible deterioration of the multiple sclerosis.

What is stem cell pre-transplant?

As a result of the detailed study of stem cells, autologous stem cell transplantation was developed and the procedure used in the treatment of immune disorders.

At first, this kind of transplantation was used to treat systemic lupus erythematosus that proved to be resistant to other kinds of therapy. In some patients, it was noticed a decrease in the activity of multiple sclerosis in the initial phase of the transplant, after cyclophosphamide and before the massive chemotherapy.

Based on these cases, the pre-transplant for multiple sclerosis and other immune disorders was developed. The patient only goes through the initial phase of the stem cell autologous transplantation called mobilization pre-transplant, what implies in taking cyclophosphamide so that there is a short-time numbness of the bone-marrow and the aim is to reach a long remission of the disease through a less risky treatment.

Today, with the knowledge and experience of treating many cases in the Nossa Senhora das Gra�as and Santa Cruz hospitals, Dr. Paulo R M de Bittencourt and his team perform the pre-transplant in their private day clinic: Unineuro.

Who is the treatment for?

This treatment is intended for patients diagnosed with multiple sclerosis and other immune disorders such as lupus, rheumatoid arthritis, spondylitis, dermatomyositis, myasthenia gravis, chronic polyneuropathy, multiple mononeuropathy and many other rare diseases, all of which present an immune mechanism that causes the disease.

To do the pre-transplant, the patient will have to undergo thorough medical evaluation and a series of examinations so as to check health conditions and, if the procedure is to take place, what care should be taken during the pre-transplant.

After the pre-transplant

After the pre-transplant, the patient will have a series of appointments with the doctor and do follow up exams to ensure the achievements of each patient are evaluated and, if needed, preventive measures are taken to keep the results achieved and reduce the probabilities the active disease returns.

Results achieved with the pre-transplant

The pre-transplant has brought hope to many patients and the real possibility of living a good healthy life simply because the disease does not progress anymore as well as because some lesions improve.

The chance of a long remission has been proven to be very possible. It is a proven result achieved in a group of 50 patients with multiple sclerosis and amyotrophic lateral sclerosis in whom Dr Paulo R M de Bittencourt performed the pre-transplant.

Among these 50 patients, we highlight some special cases:

One patient, currently 51 years old, is in definitive remission eight years after receiving a high dose of cyclophosphamide, slightly smaller than that used during the TACT mobilization phase (see Bittencourt and Gomes da Silva, Acta Neurological Scandinavica, March 2005).

Another patient, 30 years old, received the full dose and collected stem cells in January 2005. There were no serious complications and the patient is now without any symptoms and without any medication. In both cases, the oncologist that aided Dr Paulo R M de Bittencourt was Dr Valdir Furtado.

In 2007 a patient, with diagnosed multiple sclerosis for over 23 years, underwent the pre-transplant in Unineuro. Currently, the disease has stopped and, surprisingly, some lesions previously recorded in MRI are not present anymore.

What is the present position of pre-transplant?

Due to the positive results of the use of cyclophosphamide in the pre-transplant, the same procedure can be used in the treatment of many immune disorders, even chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. These results are reinforced with the demonstration in animals that cyclophosphamide in high doses is immunoablative without being myeloablative. Neutropenia, infection, early menopause, loss of hair, phlebitis and hemorrhagic cystitis may occur. We found no reports of any deaths or serious complication during the TACT mobilization phase in over 700 patients reported in international literature or in cases published until December 2008 of patients with other neurological diseases subjected to the procedure.

High doses of cyclophosphamide may lead to prolonged remissions apparently definitive in patients with multiple sclerosis and immune disorders. It is estimated that 50% of all patients with MS will have a remission of over 5 years, what makes this the most effective, less toxic and cheapest of all currently available treatments for MS and for severe immune disorders.

In literature, there is wide evidence that safety is also great. Provided proper care is taken in selecting the patients and good-quality hospital care is given during treatment, mortality in multiple sclerosis is to be zero. Patients with other diseases run a mortality risk that will vary according to their general health. The good prognosis in multiple sclerosis is due to the fact that these patients, as a rule, are in good general health conditions because their disease is restricted to the central nervous system. Patients carrying diseases as systemic lupus erythematosus may have kidney, heart and lung complications. However, it will always be a procedure far less dangerous than TACT. As the pre-transplant allows stem cells to be collected, it is possible that patients who do not have a prolonged remission can follow TACT a procedure that, nevertheless, has a high cost, extensive morbidity and a mortality of almost 10% overseas and almost 20% in Brazil (Globo Reporter, January 2005).

The treatment of immune disorders is radically changing in 2007 and 2008 as the monoclonal antibodies called MABs surface. Other articles on the site will explain what are monoclonal antibodies and their use in this cluster of diseases.

Prof. Dr. Paulo RM de Bittencourt, PhD

Translated and adapted by Marilia Bittencourt � May, 2009