Development of hematopoietic stem cell transplantation in thetreatment of autoimmune diseases

Overview

Intractable forms of autoimmune diseases (AID) follow a rapid course, with significantly shortened life expectancy, sometimes comparable to malignant diseases. Immunoablative therapy including high dole cytotoxic agents and haematopoietic autologous stem cell rescue was recently introduced as an aggressive approach to clinical practice for the treatment of AID resistant to conventional type of therapy. Autologous haematopoietic stem cell transplantation (HSCT) in humans offers rather long lasting immunosupression than reeducation of lymphocytes. On the contrary, allogeneic transplantation may replace the whole immune system. However, this attractive approach is still associated with considerable morbidity and mortality and is not justified yet for treatment of AID. The most frequent indication for immunoablative treatment is multiple sclerosis (MS), currently being reported over 100 patients to the regisrrecs worldwide. Systemic sclerosis (SSc) is the second most indicated disease as it often includes forms with not known effective conventional treatment. Results of immunoablative treatment in both diseases are encouraging with documented responses and with toxicity adequate to late stages of diseases in which esere patients accepted for this experimental type of therapy. The data are matured enough to open comparative randomized studies including immunoablative treatment versus conventional type to validate the benefit of the aggressive approach. Recently such randomized trial involving SSc has been launched (ASTIS) and a trial involving MS is under preparation. Considerably less experience is with immunoablative treatment in systemic lupus erythematodus (SLE), rheumatoid arthritis (RA) and other disorders with autoimmune patophysiology. Nonmyeloablative allogeneic transplantation or submyeloblative high dole cyclophosphamide without stem cell support are alternative approaches in the treatment of AID which could be also explored in pilot studies.

Key words:
transplantation, hematopoietic stem cell, autoimmune disease, toxicity, immunoablative treatment