TREATMENT OF AUTOIMMUNE-DISEASE BY INTENSE IMMUNOSUPPRESSIVE CONDITIONING AND AUTOLOGOUS HEMATOPOIETIC STEM-CELL TRANSPLANTATION

Citation
Rk. Burt et al., TREATMENT OF AUTOIMMUNE-DISEASE BY INTENSE IMMUNOSUPPRESSIVE CONDITIONING AND AUTOLOGOUS HEMATOPOIETIC STEM-CELL TRANSPLANTATION, Blood, 92(10), 1998, pp. 3505-3514
Citations number
42
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
92
Issue
10
Year of publication
1998
Pages
3505 - 3514
Database
ISI
SICI code
0006-4971(1998)92:10<3505:TOABII>2.0.ZU;2-9
Abstract
Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthr itis are immune-mediated diseases that are responsive to suppression o r modulation of the immune system. For patients with severe disease, i mmunosuppression may be intensified to the point of myelosuppression o r hematopoietic ablation. Hematopoiesis and immunity may then be rapid ly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 pati ents with these autoimmune diseases, autologous hematopoietic stem cel ls were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophos phamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) sele ction and reinfused after either myelosuppressive conditioning with cy clophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total bod y irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophospham ide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone h emtopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/mu L (0.5 x 10(9)/L) and a nontransfused platelet count greater than 20,000/mu L (20 x 10(9)/L) o ccurred on day 10 and 14, respectively. Regimen-related nonhematopoiet ic toxicity was minimal. All patients improved and/or had stabilizatio n of disease with a follow-up of 5 to 17 months (median, 11 months). W e conclude that intense immunosuppressive conditioning and autologous T-cell-depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabili zation or improvement. (C) 1998 by The American Society of Hematology.