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High-dose cyclophosphamide without stem cell rescue in scleroderma

C V Tehlirian¹, L K Hummers¹, B White², R A Brodsky¹, F M Wigley¹

¹ Department of Medicine, Johns Hopkins Medical Institution, Baltimore, Maryland, USA
² MedImmune, Gaithersburg, Maryland, USA

Professor F M Wigley, Division of Rheumatology, 5200 Eastern Avenue, Suite 4100, Mason F. Lord Building, Center Tower, Baltimore, MD 21224, USA; fwig{at}jhmi.edu

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 µg/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.

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