Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation. Blood 1998 Nov 15;92(10):3505-14
Date
11/10/1998Pubmed ID
9808541Scopus ID
2-s2.0-0032533235 (requires institutional sign-in at Scopus site) 200 CitationsAbstract
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.
Author List
Burt RK, Traynor AE, Pope R, Schroeder J, Cohen B, Karlin KH, Lobeck L, Goolsby C, Rowlings P, Davis FA, Stefoski D, Terry C, Keever-Taylor C, Rosen S, Vesole D, Fishman M, Brush M, Mujias S, Villa M, Burns WHMESH terms used to index this publication - Major topics in bold
Activities of Daily LivingAdult
Antigens, CD34
Antilymphocyte Serum
Arthritis, Rheumatoid
Autoimmune Diseases
Combined Modality Therapy
Cyclophosphamide
Female
Granulocyte Colony-Stimulating Factor
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cell Transplantation
Humans
Immune Tolerance
Immunosuppressive Agents
Lupus Erythematosus, Systemic
Methylprednisolone
Middle Aged
Multiple Sclerosis
Transplantation Conditioning
Transplantation, Autologous
Treatment Outcome
Whole-Body Irradiation
