Cell therapy of multiple sclerosis
In St. Petersburg, patients with multiple sclerosis are treated with stem cells and chemotherapy
The First honey revives the method of treating severe autoimmune diseases with the help of transplantation of their own stem cells. So far, it is being used for patients with multiple sclerosis as part of clinical testing. Although the method already has its own history.
Multiple sclerosis (MS) is an autoimmune disease in which the myelin sheath of the nerve fibers of the brain and spinal cord is affected, which leads to severe motor and other disorders up to deep disability.
Alexey Polushin, Ph.D., neurologist at the Research Institute of Pediatric Oncology, Hematology and Transplantology, told Dr. Peter about how autoimmune diseases are treated in Russia and abroad today with the help of high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation. Gorbacheva, assistant of the Department of Neurology of PSPbSMU. Pavlova.
– Alexey Yurievich, stem cell transplantation to patients with such an autoimmune disease as multiple sclerosis began to be engaged in the world at the very beginning of this century. And very quickly it was abandoned. Why did you return to this method?
– In the difficult 1990s and the "creative" (medically speaking) 2000s, our doctors developed a negative reaction to the concepts of "stem cells" and "transplantation". But not for those who really work with them, saving lives, including children's. I'm talking about hematologists and oncologists. And now we are talking about the technologies created by them, and not about the concept of "stem cell treatment" replicated today, by which it is not known what is meant.
Initially, it was they who promoted this method and continue to apply it, using the principle of treating hematological oncological diseases: with the help of high-dose immunosuppressive therapy, the bone marrow was "reset", and then a donor transplant was transfused. Then it became clear that the method of allogeneic (donor) hematopoietic stem cell transplantation (HSCT) is accompanied by a high incidence of complications and mortality.
That is, at the beginning of the century, problems remained, and today little has changed... Since transplantation was perceived as a therapy of despair, it was prescribed to those who were not helped by drug therapy. And these are years. As a result, the effectiveness of transplantation looked, to put it mildly, low, especially taking into account the expectations of patients who thought that after it they would start running.
The experience of the last 20 years of using HSCT for the treatment of autoimmune diseases has shown that it is not necessary to "reset" the bone marrow using "rigid" modes of immunosuppressive therapy (chemotherapy, or as doctors say, conditioning), as in oncohematological diseases. And when they started using autotransplantation — the transplantation of the patient's own stem cells after "soft" chemotherapy regimens, everything fell into place. Today, hematologists specializing in the treatment of autoimmune diseases say that the most effective therapy is the one carried out at the onset of the disease, because it corresponds to the neurological principle – "time is the brain".
– What do you know about the fate of those patients who underwent transplantation at that time?
– The experience of using hematopoietic stem cell transplantation for patients with multiple sclerosis has about the same history as PITRS (drugs that change the course of multiple sclerosis). A total of 45 people received treatment with its use at our university. I communicate and meet with people who had a transplant more than 15 years ago. Among those who underwent treatment in the 2000s, there are several people who were applied the method on time. In the spring, a woman came to me, who was 37 years old and had a TSC. Now she is 51 years old — she ran in heels, she now has no restriction of functions, only minimal symptoms detected during neurological examination, which corresponds to 1 point on the EDSS scale (this scale is used to assess the degree of disability of the patient, in which up to 4.5 points — fully preserved mobility, above 7 — deep disability — Approx. ed.). That is, everything, including HSCT, must be done on time and according to indications, and then success will be, because with multiple sclerosis, a simple formula works – the fewer foci in the brain, that is, the lower the degree of disability, the more effective treatment is if it is prescribed in a timely and purposeful manner.
In those patients who were transplanted at the Gorbacheva Research Institute with 6-7 points on the EDSS scale, the neurological status increased from 0 to 1.5 points over this long period. This suggests that anti-inflammatory therapy still played a role, and the progression of the disease in most of them at least slowed down. Therefore, in addition to the hematology service, the determination of neurologists who participated in the fate of patients and recommended this method of treatment requires great respect.
– If previously patients with multiple sclerosis were referred to HSCT when drug therapy was already ineffective, how is this happening now?
– Most patients find us by themselves. However, without the help of classical neurology, it is wrong to make a decision on the use of HSCT. We are often approached by patients who were diagnosed with multiple sclerosis only yesterday, who are not suitable for PITRS due to undesirable manifestations, or those who have not been able to get medicines in their region for years. Two years ago, we were contacted by a patient from the Arkhangelsk region who had been waiting in line for 4 years to receive a banal interferon (1st line of PITRS therapy). Here the method of TGSC was not the method of choice, in his opinion, it became the only way out of the current situation.
Of course, when communicating with a patient, we first try to clarify that the principles of care for patients with multiple sclerosis that exist in our country are fully justified, and sometimes patients are receiving PITRS for a long time without relapses of the disease. If the patient insists, additional diagnostics and scrupulous work of specialists are necessary to determine the indications for using the method and exclude other diseases similar to multiple sclerosis.
– You emphasize that before HSCT was carried out on "hard" chemotherapy. How is it being held today?
– Super-high-dose chemotherapy is not carried out, the effect in autoimmune diseases is achieved by lower doses. That is, all the same, with the help of chemotherapy drugs, we "kill" autoimmune lymphocytes, suppress the cause of the development of the disease – the pathological activity of the immune system, which supports the inflammatory process in the brain, because of which myelin, the protective shell of neurons, is affected. Relatively speaking, with HSCT, the same thing happens as when taking PITRS of the 2nd line, just the dose of the drug is much higher. But it is important to understand that the seed of multiple sclerosis is not sown in the nervous system, but on the other side of the blood-brain barrier, which is difficult to overcome. But this is exactly what gives us the opportunity to influence the main cause that triggers aggression towards myelin – that is, the blood and lymphatic system. In other words, we do not extinguish the fire, but stop putting firewood in it — we reduce the number of autoimmune lymphocytes and antibodies in the blood.
Therefore, it should be understood that it is not transplantation that has the main therapeutic effect, but a high dose of an immunosuppressive drug. Therefore, in order not to frighten those who got stuck in the 1990s, it is better to use the concept of "high-dose immunosuppressive therapy (VIST) followed by autologous hematopoietic stem cell transplantation – (VIST + ATGSK)". Nevertheless, immunosuppression without transplantation is fraught with the fact that in a certain percentage of cases the bone marrow may not recover, and this is a high risk of death: any immunosuppression leads to the activation of "dormant" viruses in the body. To prevent this from happening, stem cell transplantation is needed after it, with the help of which a faster recovery of blood parameters is achieved in response to the suppression of immunity by chemotherapy. Another important role of the THSC itself is immune reconstruction (in the common people, the "restart" of the immune system): we inject a person with his own hematopoietic stem cells (CD34+), which have not yet passed into the stage of lymphocytes.
– And what is the point in autoimmune diseases to transfuse their cells? The body will produce the same.
– We cannot yet prove that multiple sclerosis is a genetically determined disease, although we know about the potential immunogenetic predisposition to this disease. If the question of using auto-HSCT to a patient with a "familial" form of multiple sclerosis were considered, then there would really be less logic in autotransplantation. Now we are talking about the importance of achieving the so-called immune "reset" with moderate doses of chemotherapy and with transfusion of the patient's own cells without serious complications, for example, a "graft versus host" reaction.
– What should a patient who would like to do a transplant do?
– Still, I would like the motivation for its implementation to come from the attending physician. If at all previous stages of treatment the possibilities are exhausted and the neurologist decides to conduct HSCT for neurological indications, then the readiness for treatment in a hematological transplant hospital (and in no other way) consists of the absence of active inflammatory and severe concomitant pathology.
– What is the process of transplantation? It sounds scary...
– After the stage of confirming the diagnosis, analyzing the "pros" and "cons" criteria, preparing for HSCT, the patient is hospitalized in the hematology department. There, for several days, with the help of special drugs, the release of stem cells (CD34+) from the bone marrow into the peripheral blood is stimulated, and they are taken using an apheresis apparatus (as in blood donation).
While the resulting cells are being prepared for transplantation, the patient's bone marrow is restored. At the next stage, high-dose immunosuppression (administration of a chemotherapy drug) is performed, and then transfusion of the patient's own previously harvested cells into the vein. Thus, this is not a surgical operation in the classical sense, but a complex therapeutic operation. Then the stage of restoring blood parameters begins, which change as a result of chemotherapy. Hospitalization lasts a total of no more than 30 days.
– There are quite a lot of autoimmune diseases, it's not just multiple sclerosis, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, vasculitis, antiphospholipid syndrome, etc. Are attempts being made to treat them in the same way?
– Indeed, about 100 autoimmune syndromes and diseases have already been described. Therapeutic approaches to them are similar, and in the "transplant world" they are actively and effectively used. Our university, for example, recently successfully performed such treatment for a patient suffering from both scleroderma and lupus erythematosus. Officially, the Registry of the European Community for Bone Marrow Transplantation (EBMT), where we also submit data, has registered more than 3,000 transplantations for autoimmune diseases. More than 1300 of them were performed in patients with multiple sclerosis, about 800 – with connective tissue diseases, more than 220 – with inflammatory bowel diseases. It has been established that the risk of this procedure in other severe autoimmune diseases is higher, because, unlike multiple sclerosis, they often affect internal organs.
Reference
The first HSCT for autoimmune diseases in our country was performed at the Research Institute of FKI in Novosibirsk in 1998. St. Petersburg professors Andrey Novik and Boris Afanasyev were also at the origins of the TSCC for multiple sclerosis. The first dissertation on this topic in Russia was defended in 2006 at the PSPbSMU named after. Pavlova. In St. Petersburg, the treatment of patients with multiple sclerosis was initially carried out in cooperation with neurologists at the R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, as a member of the European Society for Blood and Bone Marrow Transplantation (EBMT).
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