Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I–II study

Abstract

Summary. Haematopoietic stem cell transplantation (HSCT) has been proposed for refractory autoimmune diseases, including systemic sclerosis (SSc). A sequential Bayesian phase I–II clinical trial was conducted in SSc patients to assess the feasibility, the tolerance and the efficacy of autologous HSCT. Peripheral blood stem cells (PBSC) were collected using cyclophosphamide (4 g/m²) and recombinant human granulocyte colony‐stimulating factor (5 µg/kg/d) and reinfused after positive CD34⁺ selection. Conditioning used cyclophosphamide (200 mg/kg) or melphalan (140 mg/m²) according to cardiac function. The main end‐point was the failure of the procedure, defined by failure of either PBSC mobilization, CD34⁺ selection or intensification procedure, or by procedure‐related death. Among the 12 enrolled patients, three failures occurred: one PBSC mobilization, one CD34⁺ selection and one CD34⁺ intensification. Probability of graft failure was estimated at 0·286 (95% confidence interval: 0·095–0·54). Autologous PBSC (n = 10) or bone marrow (n = 1) transplantation was actually performed in 11 patients with one procedure‐related death. Median time to neutrophil (> 0·5 × 10⁹/l) and platelet (> 25 × 10⁹/l) haematopoietic reconstitution was 12 and 10 d respectively. After 18 months (range 1–26), eight out of 11 patients have shown major or partial response. Non‐myeloablative conditioning, followed by a T cell‐depleted autologous PBSC or bone marrow transplantation, appears feasible with low toxicity in severe SSc with short‐term clinical benefits.