title: Autologous stem cell transplantation for systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is responsive to treatment with immunosuppressives and steroids, but often pursues a relapsing or refractory course resulting in increasing incapacity and reduced survival. Autologous stem cell transplantation (ASCT) following immunoablative chemotherapy is a newer therapy for autoimmune disease of potential use in severe SLE. A retrospective registry survey was carried out by the European Blood and Marrow Transplant and European League Against Rheumatism (EBMT/EULAR) registry. Data was collected from 53 patients with SLE treated by ASCT in 23 centres. Disease duration before ASCT was 59 (2-155) months (median, range), 44 (83%) were female, and median age was 29 (9-52) years. At the time of ASCT a median of seven American College of Rheumatology (ACR) diagnostic criteria for SLE were present (range 2-10) and 33 (62%) had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor in 93% of cases. Ex vivo CD34 stem cell selection was performed in 42% of patients. Conditioning regimens employed cyclophosphamide in 84%, anti-thymocyte globulin in 76% and lymphoid irradiation in 22%. The mean duration of follow-up after ASCT was 26 (0-78) months. Remission of disease activity (SLEDAI < 3) was seen in 33/50 (66%; 95%CI 52-80) evaluable patients by six months, of which 10/31 (32%; 95%CI 15-50) subsequently relapsed after six (3-40) months. Relapse was associated with negative anti-double stranded DNA (anti-dsDNA) antibodies before ASCT (P = 0.007). There were 12 deaths after 1.5 (0-48) months, of which seven (12%; 95%CI 3-21) were related to the procedure. Mortality was associated with a longer disease course before ASCT (P = 0.036). In conclusion, this registry study demonstrates the efficacy of ASCT for remission induction of refractory SLE, although mortality appeared high. The safety of this procedure is likely to be improved by patient selection and choice of conditioning regimen. The return of disease activity in one-third of patients might be reduced by long-term immunosuppressive therapy post-ASCT.
authors.affiliation: Department of Medicine, Addenbrooke's Hospital, Cambridge, UK. dj106@cam.ac.uk
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mesh_terms: D000293:Adolescent; D000328:Adult; D016009:Chi-Square Distribution; D002648:Child; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome