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 immunoablat ive as opposed to myeloablative conditioning regimen for the autotransplant of severe immunomediated diseases, We enrolled patients affected by system ic lupus erythematosus (SLE: 3 patients), by autoimmune thrombocytopenic pu rpura (AITP: one patient), by thrombotic thrombocytopenic purpura (TTP: one patient), by pure red cell aplasia (PRCA: one patient), and by a severe cr yoglobulinemia tone patient). All patients were mobilized with cyclophospha mide (Cy)4 g/m(2) + G-csf, Conditioning regimen consisted of Cy 50 mg/kg/da y (days -6 and -5); anti-T-globulin (ATG) 10 mg/kg/day and 6-methylpredniso lone (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 b elow 0.5 x 10(9)/I, while a PLT count below 20 x 10(9)/I was registered in two patients. Extrahematological toxicity was Very low. Four patients (2 SL E, 1 TTP, I cryoglobulinemia) are in complete corticosteroid-free remission with a median follow up of 335 days, The third SLE patient improved consid erably; however, he still needs low-dose corticosteroid maintenance. The AI TP and PRCA patients achieved a CR but soon relapsed; nevertheless, the pro cedure restored a steroid-sensitive status. The use of this immunoablative conditioning regimen in auto-HSCT transplant was shown to be effective in c ontrolling disease progression and could be a valuable strategy in reducing TRIM, Am, (C) 2001 Wiley-Liss, Inc.