Background Recent phase II study demonstrated that autologous hematopoietic stem cell transplantation (auto-HSCT) is more effective than conventional intravenous cyclophosphamide in the treatment of severe systemic sclerosis (SSc). However, the long-term results of CD34-selectiod or unmanipulated auto-HSCT for SSc has not been investigated.

Objectives The aim of this study is to investigate the long-term results of auto-HSCT for severe SSc and to compare efficacy of CD34-selected auto-HSCT with that of unmanipulated auto-HSCT.

Methods Nineteen patients (4 male and 15 female) with severe SSc were enrolled. Peripheral blood stem cells (PBSCs) were mobilized with cyclophosphamide (CY, 4 g/m²) and G-CSF. After collecting PBSCs more than 2×10⁶CD34+cells/kg by apheresis, CD34+ cells were immunologically selected in 11 patients. All of the patients were treated with high-dose CY (200 mg/kg) and received CD34-selected (n=11; a group with CD34-selection) or unmanipulated (n=8; a group without CD34-selection) auto-HSCT. Immune reconstitution was evaluated serially by analyzing lymphocyte subpopulations for 36 months after HSCT.

Results There was no treatment-related mortality. As toxicity, there were a variety of post-transplant infections such as adenoviral hemorrhagic cystitis, herpes zoster and cytomegaloviral antigenemia. Sclerosis of the skin was markedly improved in all of the patients within 6 months and the improvement was sustained for 60 months after auto-HSCT. Vital capacity was significantly increased at 48 months after HSCT and KL-6, a marker for interstitial pneumonia (IP), was significantly decreased in patients with IP during 12-60 months after HSCT. A titer of anti-Scl-70 was significantly decreased during 1-60 months after HSCT. Progression-free and overall 5-year survivals were 68 and 95%, respectively. Interestingly, the reduction of the skin scores was significantly greater and viral infections were more frequent in the patients with CD34-selection than those without. Effect of auto-HSCT on interstitial pneumonia, and the recovery of lymphocyte subpopulations after auto-HSCT were not significantly different between two groups.

Conclusions Auto-HSCT had long-term effects on skin sclerosis and IP, resulting in improved prognosis in patients with severe SSc. CD34-selected auto-HSCT had greater effect on skin sclerosis than unmanipulated auto-HSCT.

1. Tsukamoto H, Nagafuji K, Horiuchi T, et al. A Phase I-II Trial of Autologous Peripheral Blood Stem Cell Transplantation in the Treatment of Refractory Autoimmune Disease. Ann Rheum Dis. 65: 508-14, 2006.

2. Tsukamoto H, Nagafuji K, Horiuchi T, et al. Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4+ T cells. Rheumatology 2011; 50: 944-52.

Disclosure of Interest None Declared