title: Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients.
abstract: OBJECTIVE
  To determine the safety and long-term efficacy of immune ablation and autologous hematopoietic stem cell transplantation (HSCT) in severe systemic lupus erythematosus (SLE).
  
  
  METHODS
  Fifteen patients with persistently active SLE after intravenous (IV) cyclophosphamide (CYC) therapy underwent HSCT. Stem cells were mobilized with CYC (2.0 gm/m(2)) and granulocyte colony-stimulating factor (5 microg/kg/day). Lymphocytes were depleted from the graft by selection of CD34-positive cells. The conditioning regimen used was CYC (200 mg/kg), antithymocyte globulin (90 mg/kg), and methylprednisolone (3 mg/kg). Outcome was evaluated by the SLE Disease Activity Index (SLEDAI), serum complement levels, serologic features, function of diseased organs, and immunosuppressive medication requirements.
  
  
  RESULTS
  Fifteen patients with persistent, severe SLE, 7 of whom were critically ill, were treated. No deaths occurred following treatment. The median followup after HSCT has been 36 months (range 12-66 months). All patients demonstrated a gradual, but marked, improvement. The SLEDAI score has declined to <or=5 in 12 patients. Complement and anti-double-stranded DNA levels have normalized and marked improvements in end organ function have occurred in all subjects. Of the 12 patients followed up for >1 year after HSCT, 10 have discontinued immunosuppressive medications, and the prednisone dosage has been tapered to 15 mg/day in 1. Only 2 patients have demonstrated clinical evidence of recurrence of active lupus. One of these patients currently requires no immunosuppressive medication and has a normal performance status. The other patient is currently receiving IV CYC.
  
  
  CONCLUSIONS
  In patients experiencing the persistence of organ-threatening lupus following standard, aggressive therapy, HSCT may be performed safely, with marked improvement and sustained withdrawal of all immunosuppressive medication for most patients. A phase III randomized trial is warranted to determine the relative efficacy and durability of remission of HSCT compared with standard therapies.
authors.affiliation: Northwestern Memorial Hospital and Northwestern University School of Medicine, Chicago, Illinois, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Traynor
authors.forename: Walter G
authors.initials: WG
authors.lastname: Barr
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rosa
authors.forename: Julianne
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Yu
authors.initials: Y
authors.lastname: Oyama
authors.forename: Steven
authors.initials: S
authors.lastname: Baker
authors.forename: Mary
authors.initials: M
authors.lastname: Brush
authors.forename: Richard K
authors.initials: RK
authors.lastname: Burt
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008180:Lupus Erythematosus, Systemic / Q000628:therapy*; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage; D012449:Safety; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D011239:Prednisolone