Neue Wege in der PPMS-Behandlung: aHSCT im Fokus
In the context of PPMS treatment, the possibilities of immunotherapy come into particular focus.
In addition to the therapeutic approaches (established particularly in relapsing-remitting MS), which include symptomatic therapy and relapse therapy, the focus in PPMS treatment is primarily on immunomodulatory forms of therapy. In addition, there are other treatment options that can have a positive impact on the clinical picture, such as measures to improve lifestyle as well as rehabilitative, complementary and alternative procedures.
Es sei angemerkt, dass auf dieser Webseite speziell auf die symptomatische Therapie und Schubtherapie nicht näher eingegangen wird, um den Fokus verstärkt auf die immuntherapeutischen Möglichkeiten im Zusammenhang mit PPMS zu legen. Die Behandlung der PPMS mit der autologen Stammzelltransplantation wird in diesem Abschnitt als Immuntherapien näher beschrieben.
aHSCT:
A promising immunotherapy
Both genetic predisposition and certain environmental factors play a role in the development of multiple sclerosis (MS). For example, research shows that infection with the Epstein-Barr virus (EBV) can lead to maldevelopment of the immune system, which promotes auto-aggressiveness towards the central nervous system. Other risk factors include vitamin D deficiency in childhood, early obesity and smoking.
The idea of aHSCT as a therapy for MS is based on these findings: An immune system that is misdirected due to genetic predisposition and environmental factors is destroyed by chemotherapy and a new immune system is built up using new, own stem cells that is no longer exposed to the same environmental factors as before. In theory, this newly developed immune system still contains genetic risk factors for the development of MS, but these risk factors no longer lead to autoimmunity to the central nervous system at best without the presence of the triggering environmental factors. They would only show up if a triggering environmental situation occurs again.
aHSCT is a treatment method originally developed for blood cancers. It is mainly used in patients with lymphoma, leukemia and multiple myeloma, but usually with blood from blood donors (allogeneic as opposed to autologous). The procedure allows for a higher dose of chemotherapy by taking the body's own stem cells from the bone marrow or peripheral blood, freezing or cooling them, and returning them later. This can increase the effectiveness of the treatment and reduce toxicity. During autologous stem cell transplantation, the immune cells are almost completely killed. For this reason, it is considered the strongest possible immunotherapy for autoimmune diseases such as multiple sclerosis. During this procedure, a large part of the immune system is destroyed and rebuilt by returning the stem cells. Treatment consists of three phases: cell collection, high-dose chemotherapy and stem cell transplantation, followed by the recovery phase and aftercare. There is a difference between autologous transplantation with your own stem cells and allogeneic transplantation with stem cells from external donors. For multiple sclerosis, only autologous transplantation is used because it has a lower risk of rejection and complications.
Efficacy of aHSCT in progressive MS
There are various studies and publications that... suggest that aHSCT is an effective therapy for progressive MS and is able to stop disability progression and sustainably improve symptoms. However, the data situation is still comparatively thin and, as is often the case, the comparability of the figures published in the studies is only possible to a very limited extent. This is due, among other things, to the fact that the criteria regarding age, degree of disability (EDSS), chemotherapy used, age of the studies, observation periods, etc. are very heterogeneous in the studies and publications. For example, periods from 1 year after aHSCT to 8 years can be found in the follow-up review. Not surprisingly, the percentage reports of success of aHSCT in stopping disability progression in people with PPMS vary widely. For example, with a 46% [Muraro PA et al.] and 78% [HSCT Mexico] probability of stopping progression, the range is very wide.
The same applies to the risks associated with aHSCT. Ultimately, the procedure is based on high-dose chemotherapy. Overall, most of the possible side effects of aHSCT can be easily controlled and treated. The number of serious side effects during aHSCT has been significantly reduced over the last 20 years by improving the procedure and pretreatment and more intensive post-treatment and follow-up after transplantation.
The different transplant centers use different high-dose chemotherapy (so-called conditioning) before the autologous transplant. BEAM/anti-thymocyte globulin (ATG) or high-dose cyclophosphamide/ATG are most commonly used. More intensive regimens have more side effects. There is no clear recommendation for conditioning, but a less toxic option, cyclophosphamide/ATG, is more commonly used in MS.
A particularly gentle variant of aHSCT has been used for many years in Mexico at the Clinica Ruiz, which specializes in autoimmune diseases. Mortality in Mexico is reported to be 0.2% in 500 patients and serious side effects are largely excluded. In Mexico, high-dose chemotherapy based on cyclophosphamide is divided into 2×2 days in order to reduce the strain on the body (especially the organs) and to better control possible side effects.
Langfristige Wirkung: Die aHSCT zielt darauf ab, das Immunsystem des Patienten neu zu starten, indem es die autologen Stammzellen verwendet. Es wird angenommen, dass diese Behandlung eine langanhaltende Wirkung haben kann, möglicherweise über viele Jahre hinweg.
Currently in focus
msc and hsct
In combination, first the HSCT then the MSC, more precise studies are not yet known but at the moment many are working hard on it, the MSC is not permitted in Germany and probably not in Europe either and therefore has to be done abroad.
