Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis.
OBJECTIVE
Systemic sclerosis (SSc) is a generalised autoimmune disease, causing morbidity and a reduced life expectancy, especially in patients with rapidly progressive diffuse cutaneous SSc. As no proven treatment exists, autologous haematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic strategy in patients with a poor prognosis. This study reports the effects on survival, skin and major organ function of HSCT in patients with severe diffuse cutaneous SSc.


METHODS
A total of 26 patients were evaluated. Peripheral blood stem cells were collected using cyclophosphamide (4 g/m2) and rHu G-CSF (5 to 10 microg/kg/day) and were reinfused after positive CD34+ selection. For conditioning, cyclophosphamide 200 mg/kg was used.


RESULTS
After a median follow-up of 5.3 (1-7.5) years, 81% (n = 21/26) of the patients demonstrated a clinically beneficial response. The Kaplan-Meier estimated survival at 5 years was 96.2% (95% CI 89-100%) and at 7 years 84.8% (95% CI 70.2-100%) and event-free survival, defined as survival without mortality, relapse or progression of SSc, resulting in major organ dysfunction was 64.3% (95% CI 47.9-86%) at 5 years and 57.1% (95% CI 39.3-83%) at 7 years.


CONCLUSIONS
This study confirms that autologous HSCT in selected patients with severe diffuse cutaneous SSc results in sustained improvement of skin thickening and stabilisation of organ function up to 7 years after transplantation.
Vonk
M C
MC
Department of Rheumatology, Radboud University Nijmegen Medical Centre, P.O.Box 9101, 6500 HB Nijmegen, The Netherlands. M.Vonk@reuma.umcn.nl
Marjanovic
Z
Z
van den Hoogen
F H J
FH
Zohar
S
S
Schattenberg
A V M B
AV
Fibbe
W E
WE
Larghero
J
J
Gluckman
E
E
Preijers
F W M B
FW
van Dijk
A P J
AP
Bax
J J
JJ
Roblot
P
P
van Riel
P L C M
PL
van Laar
J M
JM
Farge
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011994:Recombinant Proteins; D012595:Scleroderma, Systemic / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous
D019653:Myeloablative Agonists; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide