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); anti-T-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 x 10(9)/l, while a PLT count below 20 x 10(9)/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.
Musso
M
M
UO Oncoematologia e Trapianto di Midollo, Dipartimento Oncologico La Maddalena, Palermo, Italy. mamussa@hbero.it
Porretto
F
F
Crescimanno
A
A
Bondi
F
F
Polizzi
V
V
Scalone
R
R
D000293:Adolescent; D000328:Adult; D000359:Aftercare; D018952:Antigens, CD34 / Q000032:analysis; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000633:toxicity; D001327:Autoimmune Diseases / Q000150:complications / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006760:Hospitalization; D006801:Humans; D018189:Immunomagnetic Separation; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods / Q000592:standards; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods / Q000592:standards; D016896:Treatment Outcome
D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D008775:Methylprednisolone