title: High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes.
abstract: Systemic sclerosis (SSc) is a multisystem disease of presumed autoimmune pathogenesis for which no proven effective treatment exists. High-dose immunosuppressive therapy (HDIT) has been proposed as an investigational treatment for severe autoimmune diseases. Nineteen patients with poor-prognosis SSc underwent HDIT. The median age was 40 years (range, 23-61 years), the median modified Rodnan skin score (a measure of dermal sclerosis) was 31, and the median DLCO was 57%. Conditioning therapy involved 800 cGy total body irradiation (TBI) (+/- lung shielding to approximately 200 cGy), 120 mg/kg cyclophosphamide, and 90 mg/kg equine antithymocyte globulin. CD34-selected granulocyte-colony-stimulating factor-mobilized autologous blood stem cells provided hematopoietic rescue. With median follow-up at 14.7 months, the Kaplan-Meier estimated 2-year survival rate was 79%. Three patients died of treatment complications and one of disease progression. Two of the first 8 patients had fatal regimen-related pulmonary injury, a complication not found among 11 subsequent patients who received lung shielding for TBI. Overall, internal organ functions were stable to slightly worse after HDIT, and 4 patients had progressive or nonresponsive disease. As measured by modified Rodnan skin scores and modified health assessment questionnaire disability index (mHAQ-DI) scores, significant disease responses occurred in 12 of 12 patients evaluated at 1 year after HDIT. In conclusion, though important treatment-related toxicities occurred after HDIT for SSc, modifications of initial approaches appear to reduce treatment risks. Responses in skin and mHAQ-DI scores exceed those reported with other therapies, suggesting that HDIT is a promising new therapy for SSc that should be evaluated in prospective randomized studies.
authors.affiliation: University of Colorado Health Sciences Center, Denver 80262, USA. peter.mcsweeney@uchsc.edu
authors.forename: Peter A
authors.initials: PA
authors.lastname: McSweeney
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Crofford
authors.forename: Roger
authors.initials: R
authors.lastname: Dansey
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.forename: Kevin T
authors.initials: KT
authors.lastname: McDonagh
authors.forename: J Lee
authors.initials: JL
authors.lastname: Nelson
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Leona A
authors.initials: LA
authors.lastname: Holmberg
authors.forename: C S
authors.initials: CS
authors.lastname: Chen
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wener
authors.forename: Katherine
authors.initials: K
authors.lastname: Ryan
authors.forename: Julie
authors.initials: J
authors.lastname: Sunderhaus
authors.forename: Ken
authors.initials: K
authors.lastname: Russell
authors.forename: John
authors.initials: J
authors.lastname: Rambharose
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012595:Scleroderma, Systemic / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide