WASHINGTON — Hematopoietic stem cell transplantation was associated with improvements in outcome compared to cyclophosphamide in patients with diffuse cutaneous systemic scleroderma, according to study results presented at the American College of Rheumatology Annual Meeting.
Keith Sullivan, MD, of Duke University in Durham, N.C., and colleagues, randomly assigned 36 patients to myeloablative hematopoietic stem cell transplantation and 39 patients to cyclophosphamide 750 mg/m2 per month. Myeloablation was defined as 800 cGy total body irradiation with lung and kidney shielding, 120 mg/kg cyclophosphamide and 90 mg/kg antithymocyte globulin.
“We used myeloablative transplantation because it can arrest and divide autoreactive cells,” Sullivan said.
The primary outcome measure was a global rank composite score that included mortality, event-free survival (EFS) without organ failure, lung function, the scleroderma modification of the Health Assessment Questionnaire (SHAQ), forced vital capacity and Rodnan skin score. This was assessed as an intention-to-treat outcome at 54 months.
Comparison of this composite score showed transplantation met the predefined primary endpoint at 54 months (P = .013) and 48 months (P = .008). Overall survival was 91% for transplantation and 77% for cyclophosphamide. The mortality rate was 3% for stem cell transplantation and 0% for cyclophosphamide. The median Rodnan score was 17 in the transplant group and -6 in the cyclophosphamide group. Event-free survival also favored transplant (P = .03).
The Kaplan-Meier curves for both EFS (P = .030) and OS (P = .019) were significantly different between the two groups, according to the results.
Secondary endpoint results indicated that initiation to DMARDs was 9% in the transplant group and 44% for cyclophosphamide. Rates of pulmonary hypertension were 0% in the transplant group and 15% in the cyclophosphamide group.
Serious adverse events were more common with transplantation, as was herpes zoster. Baseline data indicated there were more women and never smokers in the cyclophosphamide group.
“We found that the [global rank composite score] was a useful measure of scleroderma outcomes,” Sullivan said. “While there are risks with hematopoietic stem cell transplantation, these appear warranted given the success of the intervention and the underlying disease. SCOT [Study] supports myeloablative [hematopoietic stem cell transplantation] HSCT as a significant advance in systemic scleroderma.”
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