High-dose cyclophosphamide without stem cell rescue in scleroderma.
OBJECTIVE
To investigate the safety and tolerability of high-dose cyclophosphamide without stem cell rescue in scleroderma.


METHODS
An open-label, single-site, uncontrolled study design entered patients with active diffuse cutaneous scleroderma. Patients were treated with cyclophosphamide (50 mg/kg) intravenously daily for 4 consecutive days (total 200 mg/kg) followed by granulocyte colony-stimulating factor (5 microg/kg/day). The primary clinical efficacy end point was the modified Rodnan skin score (mRSS). Secondary end points included the Health Assessment Questionnaire-Disability Index (HAQ-DI), physician global assessment (PGA) and pulmonary function tests.


RESULTS
Six patients (4 men, 2 women) aged 19-60 years were entered into the study. One patients died early in the protocol, thus five patients had follow-up data. The percentage reduction of the mRSS in these five evaluable patients within 1 month of treatment was 60%, 55%, 41%, 31% and 0%. The patient with no decline in skin score at 1 month showed a decrease in skin score from 41 to 26 by the 3-month visit, a 37% improvement. Three patients sustained the improvement after treatment for 24, 12 and 12 months. Two patients relapsed at 12 and 6 months after treatment. The PGA and HAQ-DI scores improved in five of the six patients by 72% and 79% respectively at 3 months. The only serious adverse event was a death that occurred owing to infection after neutrophil count recovery.


CONCLUSIONS
High-dose cyclophosphamide without stem cell rescue can lead to a clinically significant improvement in skin score and measures of disease severity in patients with diffuse cutaneous scleroderma.
Tehlirian
C V
CV
Department of Medicine, Johns Hopkins Medical Institution, Baltimore, Maryland, USA.
Hummers
L K
LK
White
B
B
Brodsky
R A
RA
Wigley
F M
FM
D000328:Adult; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012594:Scleroderma, Localized / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000473:pathology; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide