Vonk M C, Marjanovic Z, van den Hoogen F H J, Zohar S, Schattenberg A V M B, Fibbe W E, Larghero J, Gluckman E, Preijers F W M B, van Dijk A P J, Bax J J, Roblot P, van Riel P L C M, van Laar J M, Farge D
Department of Rheumatology, Radboud University Nijmegen Medical Centre, P.O.Box 9101, 6500 HB Nijmegen, The Netherlands.
Ann Rheum Dis. 2008 Jan;67(1):98-104. doi: 10.1136/ard.2007.071464. Epub 2007 May 25.
Systemic sclerosis (SSc) is a generalised autoimmune disease, causing morbidity and a reduced life expectancy, especially in patients with rapidly progressive diffuse cutaneous SSc. As no proven treatment exists, autologous haematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic strategy in patients with a poor prognosis. This study reports the effects on survival, skin and major organ function of HSCT in patients with severe diffuse cutaneous SSc.
A total of 26 patients were evaluated. Peripheral blood stem cells were collected using cyclophosphamide (4 g/m2) and rHu G-CSF (5 to 10 microg/kg/day) and were reinfused after positive CD34+ selection. For conditioning, cyclophosphamide 200 mg/kg was used.
After a median follow-up of 5.3 (1-7.5) years, 81% (n = 21/26) of the patients demonstrated a clinically beneficial response. The Kaplan-Meier estimated survival at 5 years was 96.2% (95% CI 89-100%) and at 7 years 84.8% (95% CI 70.2-100%) and event-free survival, defined as survival without mortality, relapse or progression of SSc, resulting in major organ dysfunction was 64.3% (95% CI 47.9-86%) at 5 years and 57.1% (95% CI 39.3-83%) at 7 years.
This study confirms that autologous HSCT in selected patients with severe diffuse cutaneous SSc results in sustained improvement of skin thickening and stabilisation of organ function up to 7 years after transplantation.
系统性硬化症（SSc）是一种全身性自身免疫性疾病，会导致发病并缩短预期寿命，尤其是在快速进展的弥漫性皮肤型SSc患者中。由于尚无经证实的治疗方法，自体造血干细胞移植（HSCT）被用作预后不良患者的一种新治疗策略。本研究报告了HSCT对重度弥漫性皮肤型SSc患者生存、皮肤及主要器官功能的影响。
共评估了26例患者。使用环磷酰胺（4 g/m²）和重组人粒细胞集落刺激因子（rHu G-CSF，5至10 μg/kg/天）采集外周血干细胞，并在CD34+选择呈阳性后回输。预处理使用环磷酰胺200 mg/kg。
中位随访5.3（1 - 7.5）年后，81%（n = 21/26）的患者显示出临床有益反应。5年时的Kaplan-Meier估计生存率为96.2%（95%可信区间89 - 100%），7年时为84.8%（95%可信区间70.2 - 100%）；无事件生存率定义为无死亡、复发或SSc进展且未导致主要器官功能障碍的生存，5年时为64.3%（95%可信区间47.9 - 86%），7年时为57.1%（95%可信区间39.3 - 83%）。
本研究证实，在选定的重度弥漫性皮肤型SSc患者中进行自体HSCT可使皮肤增厚持续改善，器官功能在移植后长达7年保持稳定。
