High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes.
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.
McSweeney
Peter A
PA
University of Colorado Health Sciences Center, Denver 80262, USA. peter.mcsweeney@uchsc.edu
Nash
Richard A
RA
Sullivan
Keith M
KM
Storek
Jan
J
Crofford
Leslie J
LJ
Dansey
Roger
R
Mayes
Maureen D
MD
McDonagh
Kevin T
KT
Nelson
J Lee
JL
Gooley
Theodore A
TA
Holmberg
Leona A
LA
Chen
C S
CS
Wener
Mark H
MH
Ryan
Katherine
K
Sunderhaus
Julie
J
Russell
Ken
K
Rambharose
John
J
Storb
Rainer
R
Furst
Daniel E
DE
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
D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide