Objective: To investigate the safety and tolerability of high dose cyclophosphamide without stem cell rescue in scleroderma.
Methods: An open-labeled 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 endpoint was the modified Rodnan skin score (mRSS). Secondary endpoints included the Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician Global Assessment (PGA), and Pulmonary Function Tests (PFTs).
Results: Six patients (4 males, 2 females) with an age range of 19 to 60 years were entered into the study. There was one death early in the protocol, thus five patients had follow-up data. The percent reduction of the mRSS in these five evaluable patients within one month of therapy was 60%, 55%, 41%, 31%, and 0%. The patient with no decline in skin score at one month showed a decrease in skin score from 41 to 26 by the 3 month visit, a 37% improvement. Three patients have 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 due to infection after neutrophil count recovery.
Conclusions: High dose cyclophosphamide without stem rescue can lead to clinically significant improvement in skin score and measures of disease severity in patients with diffuse cutaneous scleroderma.
- stem cells
- systemic sclerosis