Intense immunosuppressive therapy followed by autologous peripheral blood selected progenitor cell reinfusion for severe autoimmune disease

Autologous stem cell transplantation (HSCT) has been shown to be effective in curing a large spectrum of autoimmune disorders. Case reports are being collected in the EBMT/EULAR Autoimmune Disease Stem Cell Project registry, which reports transplant-related mortality (TRM) of 6%. In order to reduce TRM and preserve the anti-autoimmune effect we evaluated a more immunoablative as opposed to myeloablative conditioning regimen for the autotransplant of severe immunomediated diseases. We enrolled patients affected by systemic lupus erythematosus (SLE: 3 patients), by autoimmune thrombocytopenic purpura (AITP: one patient), by thrombotic thrombocytopenic purpura (TTP: one patient), by pure red cell aplasia (PRCA: one patient), and by a severe cryoglobulinemia (one patient). All patients were mobilized with cyclophosphamide (Cy) 4 g/m2 + G-csf. Conditioning regimen consisted of Cy 50 mg/kg/day (days -6 and -5); antiT-globulin (ATG) 10 mg/kg/day and 6-methylprednisolone (PDN) 1 g/day (days -4, -3, and -2). Immunomagnetically selected CD34+ cells were re-infused on day 0. In three patients neutrophil count fell below 0.5 × 109/l, while a PLT count below 20 × 109/l was registered in two patients. Extrahematological toxicity was very low. Four patients (2 SLE, 1 TTP, 1 cryoglobulinemia) are in complete corticosteroid-free remission with a median follow up of 335 days. The third SLE patient improved considerably; however, he still needs low-dose corticosteroid maintenance. The AITP and PRCA patients achieved a CR but soon relapsed; nevertheless, the procedure restored a steroid-sensitive status. The use of this immunoablative conditioning regimen in auto-HSCT transplant was shown to be effective in controlling disease progression and could be a valuable strategy in reducing TRM. Am. J. Hematol. 66:75-79, 2001