Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study
Identifieur interne : 002463 ( Main/Merge ); précédent : 002462; suivant : 002464Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study
Auteurs : Ann E. Traynor [États-Unis] ; James Schroeder [États-Unis] ; Robert M. Rosa [États-Unis] ; Dong Cheng [États-Unis] ; Jakub Stefka [États-Unis] ; Salim Mujais [États-Unis] ; Steven Baker [États-Unis] ; Richard K. Burt [États-Unis]Source :
- The Lancet [ 0140-6736 ] ; 2000.
English descriptors
- Teeft :
- Abnormality, Absolute neutrophil count, Active disease, Active lupus, Antihypertensive agents, Antinuclear antibody, Antithymocyte globulin, Arthritis rheum, Articles patient, August, Autoimmune disease, Autoimmune diseases, Autologous, Autologous haemopoietic transplantation, Autologous transplantation, Bone marrow transplantation, Cell transplantation, Chronic headache, Class glomerulonephritis, Clinical evidence, Conditioning regimen, Continuous hyperfiltration, Creatinine clearance, Cyclophosphamide, Daily doses, Disease activity, Disease onset, Eligible patients, Erythematosus, Flow cytometry, Fluid overload, Haemoglobin, Haemopoietic, Immune, Immune suppression, Immune system, Interleukin, Intracellular interleukin, Intravenous, Intravenous cyclophosphamide, James schroeder, Lancet, Life technologies, Lupus, Lupus erythematosus, Lupus nephritis, Lymphocyte, Magnetic resonance imaging, Median, Median time, Normal control, Northwestern memorial hospital, Northwestern university, Oedema, Peripheral blood, Peripheral blood lymphocytes, Perkin elmer cetus, Proc natl acad, Repertoire, Salim mujais, Steven baker, Systemic, Systemic lupus erythematosus, Systemic lupus erythematosus disease activity index scores, Transplant, Transplantation, Transverse myelitis, Vital capacity.
Abstract
Summary: Background Patients with systemic lupus erythematosus (SLE) who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide, represent a subset of patients at high risk of early death. We investigated the safety and efficacy of immune suppression and autologous haemopoietic stem-cell infusion to treat such patients.Methods From 1996, we selected patients with persistent SLE despite use of cyclophosphamide. Patients underwent dose-intense immune suppression and autologous haemopoietic stem-cell (CD34) infusion. Peripheral blood lymphocytes were analysed by flow cytometry, ELISA, and T-cell-receptor spectratyping before and after transplantation. We mobilised autologous haemopoietic stem cells with 20 g/m2 cyclophosphamide and 10 g/kg granulocyte colony stimulating factor daily, enriched with CD34-positive selection, and reinfused after immunosuppression with 200 mg/kg cyclophosphamide, 1 g methylprednisolone, and 90 mg/kg equine antithymocyte globulin.Results Nine patients underwent stem-cell mobilisation but two were excluded before transplantation because of infection. The remaining seven received high-dose chemotherapy and stem-cell infusion. Median time to an absolute neutrophil count higher than 05109/L and non-transfused platelet count higher than 20109/L was 9 days (range 811) and 11 days (1013), respectively. At a median follow-up of 25 months (1240), all patients were free from signs of active lupus. Renal, cardiac, pulmonary, and serological markers, and T-cell phenotype and repertoire had normalised.Interpretation Patients remained free from active lupus and improved continuously after tranplantation, with no immunosuppressive medication or small residual doses of prednisone. T-cell repertoire diversity and responsiveness was restored. Durability of remission remains to be established.
Url:
DOI: 10.1016/S0140-6736(00)02627-1
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<front><div type="abstract">Summary: Background Patients with systemic lupus erythematosus (SLE) who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide, represent a subset of patients at high risk of early death. We investigated the safety and efficacy of immune suppression and autologous haemopoietic stem-cell infusion to treat such patients.Methods From 1996, we selected patients with persistent SLE despite use of cyclophosphamide. Patients underwent dose-intense immune suppression and autologous haemopoietic stem-cell (CD34) infusion. Peripheral blood lymphocytes were analysed by flow cytometry, ELISA, and T-cell-receptor spectratyping before and after transplantation. We mobilised autologous haemopoietic stem cells with 20 g/m2 cyclophosphamide and 10 g/kg granulocyte colony stimulating factor daily, enriched with CD34-positive selection, and reinfused after immunosuppression with 200 mg/kg cyclophosphamide, 1 g methylprednisolone, and 90 mg/kg equine antithymocyte globulin.Results Nine patients underwent stem-cell mobilisation but two were excluded before transplantation because of infection. The remaining seven received high-dose chemotherapy and stem-cell infusion. Median time to an absolute neutrophil count higher than 05109/L and non-transfused platelet count higher than 20109/L was 9 days (range 811) and 11 days (1013), respectively. At a median follow-up of 25 months (1240), all patients were free from signs of active lupus. Renal, cardiac, pulmonary, and serological markers, and T-cell phenotype and repertoire had normalised.Interpretation Patients remained free from active lupus and improved continuously after tranplantation, with no immunosuppressive medication or small residual doses of prednisone. T-cell repertoire diversity and responsiveness was restored. Durability of remission remains to be established.</div>
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