Four-Year Follow-Up after High-Dose Immunosuppressive Therapy (HDIT) for Severe Systemic Sclerosis (SSc).

To determine if sustained responses could be achieved after HDIT and rescue with autologous CD34-selected hematopoietic cells, we assessed the 4-yr outcome in patients (pts) with severe SSc. Thirty-four early (≤4 years), diffuse [mod. Rodnan skin score (mRSS) ≥16] SSc pts with predefined visceral organ dysfunction (primarily lung) were included. G-CSF was used for mobilization of peripheral blood stem cells and the autologous graft was CD34-selected. HDIT included cyclophosphamide (120 mg/kg), antithymocyte globulin (90 mg/kg) and total body irradiation (800 Gy) (with lung shielding of the last 26 pts). Neutrophil and platelet counts recovered by 9 (7–13) and 11 (7–25) days, respectively. There was a significant improvement in skin (−73%, p<0.0001) and in overall function (HAQ-DI: −56%, p<0.0001) at 4 (1–8) years in evaluable pts compared to baseline (Table). Lung, heart and kidney function, in general, remained clinically stable. Importantly, biopsies confirmed a response in skin associated with resolution or a significant decrease of dermal fibrosis. Seventeen (63%) of 27 evaluable patients surviving at least 1 year after HDIT continued to have sustained responses at 4 (1–8) yrs and required no DMARD (drug-modifying antirheumatic drug) treatment. Twelve patients died (transplant-related=8 [23%]; SSc-related=4 [12%]). Two transplant-related deaths were secondary to renal crisis events that occurred within 3 months of HDIT. The other 6 transplant-related deaths were cardiac or pulmonary toxicities (n=4), EBV-PTLD (n=1) and a myelodysplastic syndrome (n=1). The estimated overall survival was 64% at 5 yrs. In conclusion, sustained responses were observed in 63% of evaluable patients after HDIT (median: 4 yrs) and marked improvement in skin and overall function was observed in high-risk SSc pts. A decrease in skin score was associated with skin remodeling.