Mobilization of endothelial progenitor cells by intravenous cyclophosphamide in patients with systemic sclerosis.
OBJECTIVE
To evaluate the effects of i.v. CYC on the number of circulating endothelial progenitor cells (EPCs) in patients with SSc, and the potential association of the EPC response with CYC's effect for treating interstitial lung disease (ILD).


METHODS
This open-label, prospective study involved 12 patients with SSc and alveolitis (CYC group). All patients received six courses of i.v. CYC (0.5 g/m2) at 4-week intervals in combination with low-dose prednisolone. Ten patients were followed for 24 months. Seven SSc patients treated with low-dose prednisolone alone were used as a control for the EPC measurement (control group). Five patients with non-SSc CTD who received i.v. CYC and prednisolone also served as disease controls. EPCs were quantified by the partial enrichment of CD34+ cells followed by three-colour flow cytometry. The circulating levels of vascular injury markers were measured by immunoassay.


RESULTS
The EPC count was significantly increased at 2 weeks after treatment in the CYC group (P=0.02), but not in the control group, while CYC increased EPC count in all disease controls. The SSc patients in the CYC group were divided into five EPC responders and seven EPC non-responders. Circulating vascular injury markers were reduced in the responders, but not in the non-responders. During the 24-month follow-up, 3 of 10 patients developed end-stage lung disease, and all of them were EPC non-responders.


CONCLUSIONS
A low-dose i.v. CYC induces EPC mobilization, which may contribute to the efficacy for treating SSc-associated ILD.
Furuya
Yoshiaki
Y
Department of Internal Medicine, Division of Rheumatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Okazaki
Yuka
Y
Kaji
Kenzou
K
Sato
Shinichi
S
Takehara
Kazuhiko
K
Kuwana
Masataka
M
D000368:Aged; D015415:Biomarkers; D003520:Cyclophosphamide / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D017563:Lung Diseases, Interstitial / Q000188:drug therapy; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000188:drug therapy*; D013234:Stem Cells / Q000187:drug effects*; D016896:Treatment Outcome
D015415:Biomarkers; D003520:Cyclophosphamide