High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study.
More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis (SSc). A phase 2 single-arm study of high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected hematopoietic cell transplantation (HCT) was conducted in 34 patients with diffuse cutaneous SSc. HDIT included total body irradiation (800 cGy) with lung shielding, cyclophosphamide (120 mg/kg), and equine antithymocyte globulin (90 mg/kg). Neutrophil and platelet counts were recovered by 9 (range, 7 to 13) and 11 (range, 7 to 25) days after HCT, respectively. Seventeen of 27 (63%) evaluable patients who survived at least 1 year after HDIT had sustained responses at a median follow-up of 4 (range, 1 to 8) years. There was a major improvement in skin (modified Rodnan skin score, -22.08; P < .001) and overall function (modified Health Assessment Questionnaire Disability Index, -1.03; P < .001) at final evaluation. Importantly, for the first time, biopsies confirmed a statistically significant decrease of dermal fibrosis compared with baseline (P < .001). Lung, heart, and kidney function, in general, remained clinically stable. There were 12 deaths during the study (transplantation-related, 8; SSc-related, 4). The estimated progression-free survival was 64% at 5 years. Sustained responses including a decrease in dermal fibrosis were observed exceeding those previously reported with other therapies. HDIT and autologous HCT for SSc should be evaluated in a randomized clinical trial.
Nash
Richard A
RA
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. rnash@fhcrc.org
McSweeney
Peter A
PA
Crofford
Leslie J
LJ
Abidi
Muneer
M
Chen
Chien-Shing
CS
Godwin
J David
JD
Gooley
Theodore A
TA
Holmberg
Leona
L
Henstorf
Gretchen
G
LeMaistre
C Fred
CF
Mayes
Maureen D
MD
McDonagh
Kevin T
KT
McLaughlin
Bernadette
B
Molitor
Jerry A
JA
Nelson
J Lee
JL
Shulman
Howard
H
Storb
Rainer
R
Viganego
Federico
F
Wener
Mark H
MH
Seibold
James R
JR
Sullivan
Keith M
KM
Furst
Daniel E
DE
D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D005500:Follow-Up Studies; 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 / Q000628:therapy*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide