Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation

• Published in: Blood Vol. 92; no. 10; pp. 3505 - 3514
• Main Authors: BURT, R. K, TRAYNOR, A. E, STEFOSKI, D, TERRY, C, KEEVER-TAYLOR, C, ROSEN, S, VESOLE, D, FISHMAN, M, BRUSH, M, MUJIAS, S, VILLA, M, BURNS, W. H, POPE, R, SCHROEDER, J, COHEN, B, KARLIN, K. H, LOBECK, L, GOOLSBY, C, ROWLINGS, P, DAVIS, F. A
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.11.1998
• Subjects: Activities of Daily Living; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens, CD34 - analysis; Antilymphocyte Serum - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - therapy; Autoimmune Diseases - drug therapy; Autoimmune Diseases - therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Combined Modality Therapy; Cyclophosphamide - therapeutic use; Female; Granulocyte Colony-Stimulating Factor - therapeutic use; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Immune Tolerance; Immunosuppressive Agents - therapeutic use; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - therapy; Medical sciences; Methylprednisolone - therapeutic use; Middle Aged; Multiple Sclerosis - drug therapy; Multiple Sclerosis - therapy; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation; Immunopathology; Corticosteroid; Drug combination; Stem cell; Hematopoietic cell; Autoimmune disease; Methylprednisolone; Radiotherapy; Glucocorticoid; Blood; Autograft; Chemotherapy; Cyclophosphamide; Oxazaphosphinane derivatives; Nitrogen mustard; Bone marrow; Graft; Combined treatment; Immunosuppressive agent; Antithymocyte globulin
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V92.10.3505

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/microL (0.5 x 10(9)/L) and a nontransfused platelet count greater than 20,000/microL (20 x 10(9)/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We 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 stabilization or improvement.