Stammzelltherapie schwerer Autoimmunkrankheiten

Zusammenfassung

Trotz Einsatz aller konventioneller (immunsuppressiver) Therapieformen kommt es in manchen Fällen schwer verlaufender Autoimmunerkrankungen zum Fortschreiten der Erkrankung, irreversiblen Organschäden und Todesfällen. Zusätzlich kann langdauernde immunsuppressive Therapie, v. a. mit Cyclophosphamid und Kortikosteroiden, zu schweren Nebenwirkungen einschließlich einer hohen Rate an Sekundärneoplasien führen. Daher wird seit mehreren Jahren im Rahmen von experimentellen Studienprotokollen der Nutzen einer kurzfristigen dosiseskalierten Immunsuppression in Form der Hochdosischemotherapie (HDCT) mit autologer Stammzelltransplantation bei ansonsten therapierefraktären Patienten erprobt. Im Mittelpunkt dieser Bemühungen stehen bisher Patienten mit progressiver systemischer Sklerose, systemischem Lupus erythematodes, Rheumatoidarthritis, multipler Sklerose, Autoimmunhämolyse und Autoimmunthrombopenie. Auch Patienten mit primär systemischen Vaskulitiden (PSV) könnten geeignete Kandidaten für die HDCT sein. Es müssen die Patienten ausgewählt werden, bei denen die Schwere der Erkrankung, bzw. die krankheitsassoziierte Mortalität die Toxizität der HDCT erheblich überwiegt. Grundsätzlich sollten für die ASCT Patienten ausgewählt werden, deren Erkrankung therapierefraktär, aktiv und progredient ist, und bei denen ein hohes Risiko für bleibende Funktionseinschränkungen und hohe Mortalität trotz konventioneller Therapie besteht. Durch verbesserte Scoring-Systeme, die eine frühere Identifikation dieser Hochrisiko-Patienten schon in frühen Krankheitsstadien erlauben, kann zukünftig der Erfolg der Methode verbessert und die Risiken minimiert werden. Erste Publikationen sowie eigene Erfahrungen bei wenigen, ausgewählten Patienten mit schwer verlaufenden PSV und anderen Autoimmunerkrankungen zeigen, dass langfristige Remissionen auch in vormals therapierefraktären Fällen möglich sind bei akzeptabler Toxizität. Zukünftig können allein durch multizentrische Phase-III-Studien der Nutzen und die Risiken der Stammzelltransplantation im Vergleich zur konventionellen Therapie geklärt werden.

Abstract

Many patients with various autoimmune diseases fail to respond to conventional immunosuppressive therapy and develop irreversible organ damage. In some cases the complications might be fatal. Furthermore, prolonged immunosuppression with cyclophosphamide or corticosteroids often leads to long-term side effects, cumulative organ damage and development of secondary malignancies. Thus, short-term, high-dose immunosuppressive therapy with autologous stem cell transplantation (ASCT) might be an alternative for otherwise refractory patients. This concept has been used mainly for patients with scleroderma, systemic lupus, rheumatoid arthritis and multiple sclerosis, autoimmune hemolysis and thrombocytopenia. Patients with primary systemic vasculitis (PSV) also seem to be suitable candidates for high dose chemotherapy (HDCT). The patients must be identified in whom disease severity and disease-related mortality overweighs the toxicity of the high-dose chemotherapy. Only patients with active, refractory and progressing disease who are at high risk for cumulative toxicity due to conventional therapy should be eligible for ASCT. Careful patient selection with the help of scoring systems and determination of the optimal time in the course of disease are now the major goals in the approach to HDCT. First reports together with our own single center experience in HDCT with a limited number of patients with severe PSV showed that long-term remissions even in patients refractory to conventional immunosuppression are possible with acceptable toxicity. For the next years, controlled trials should be considered to determine the potential and risks of ASCT compared to conventional immunosuppressive therapy.;

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