Stammzelltherapie bei Autoimmunerkrankungen

Zusammenfassung

In den letzten Jahren wurden mehr als 1500 Patienten weltweit wegen einer bedrohlichen, therapierefraktären Autoimmunerkrankung autologe Stammzellen transplantiert. Eine aktuelle Analyse von 900 in der EBMT Datenbank registrierten Patienten zeigte ein 5-Jahres-Überleben von 85 %. 45 % der Patienten waren nach 5 Jahren progressionsfrei. Die Therapie-assoziierte Mortalität liegt je nach Erkrankung und Konditionierungsverfahren zwischen 1 und 10 %. Neben direkt immunologisch vermittelten Effekten konnte auch gezeigt werden, dass strukturelle Veränderungen, wie Sklerose oder Rarefizierung von Hautgefäßen, nach Transplantation bei Patienten mit systemischer Sklerose reversibel waren. Mesenchymale Stammzellen sind in den letzten Jahren aufgrund ihrer immunmodulatorischen Effekte und ihrer scheinbar geringen Toxizität für verschiedene Autoimmunerkrankungen eingesetzt worden. Trotz erster ermutigender Ergebnisse stehen Daten aus kontrollierten prospektiven Studien aus.

Abstract

Over 1,500 patients world wide have received a hematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease. Most of these have been autologous and mostly have occurred in the past 15 years. Over 1,000 of these have been registered in the European Group for Bone Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR) combined data base. A recent retrospective analysis of 900 patients¹ showed that the majority had multiple sclerosis (n = 345) followed by systemic sclerosis (n = 175), systemic lupus erythematosus (n = 85), rheumatoid arthritis (n = 89), juvenile idiopathic arthritis (n = 65) and idiopathic cytopenic purpura (n = 37). An overall 85 % 5-year-survival and 43 % progression-free survival was seen, with 100-day-transplant-related-mortality (TRM) ranging between 1 % (rheumatoid arthritis) and 11 % (systemic lupus erythematosus and juvenile idiopathic arthritis). Around 30 % of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many, e. g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalisation of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. The high TRM was in part related to conditioning intensity, comorbidity and age, and the final risk/benefit assessment will be made after the results of the three randomised propective clinical trials are known.
Recently, multipotent mesenchymal stromal cells have been tested in various autoimmune diseases, exploiting their immune modulating properties and apparent low acute toxicity. Despite encouraging small phase I/II studies, no positive data from randomised, prospective studies are as yet available in the peer reviewed literature.

Schlüsselwörter

Stammzelltransplantation - Autoimmunerkrankung - hämatopoietische Stammzellen - mesenchymale Stammzellen

Keywords

stem cell transplantation - autoimmune disease - hematopoietic stem cells - mesenchymal stem cells

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