Objective: To investigate the feasibility, efficacy and safety of high dose immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell transplantation (PBSCT) with CD(34)(+) cell selection in patients with refractory and severe autoimmune diseases.
Methods: Twenty-one patients with SLE, RA, pSS, SSc or MCTD were enrolled in the study from 1999. Autologous haemopoietic stem cells were mobilized with CTX 3 approximately 4 g/m(2) and granulocyte colony stimulating factor (G-CSF). CD(34)(+) cells were selected by CliniMACS. After conditioning with CTX (200 mg/kg) and pig antithymocyte globulin (ATG, 90 mg/kg) or CTX (150 mg/kg) and total body irradiation (TBI, 4 approximately 6 Gy), the enriched CD(34)(+) cells were reinfused.
Results: All patients completed the mobilization and leukapheresis procedures successfully, and proceeded to receive conditioning and transplantation. Two patients died of complication related to transplantation, one is CMV infection, the other is severe pneumonia during the course of granulocyte deficiency. A MCTD patient completed the stem cell mobilization and died of severe pulmonary hypertension and heart failure before CD(34)(+) cells reinfusing. Two SLE patients relapsed in 26, 37 months respectively and a RA patient relapsed in 15 months after transplantation. Other patients got improved, with SLE-DAI score decreasing from 17 to 4 score and proteinuria decreasing from 6.7 g to 2.3 g in SLE patients; DAS28 score from 7.9 to 2.1 in RA patient; Symptom improved and lab results recovered in SS.
Conclusion: High dose immunosuppressive therapy followed by autologous peripheral blood stem cell transplantation with CD(34)(+) cell selection is feasible and relative safe. Patients remain free from disease active and improved continuously. Some patients could relapse after transplantation. Long-term effect need to be further observed.