Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases and Department of Internal Medicine II, University Hospital Tuebingen, Tuebingen, Germany.
J Rheumatol. 2012 Feb;39(2):269-75. doi: 10.3899/jrheum.110868. Epub 2012 Jan 15.
Autologous stem cell transplantation (aSCT) for systemic sclerosis (SSc) has been shown to be effective in recent reports. This aggressive approach and the disease itself are associated with a high mortality. We report our experiences in 26 consecutive patients.
Between 1997 and 2009, 26 patients were scheduled for aSCT. Our standard transplant regimen consists of cyclophosphamide (CYC) and granulocyte colony-stimulating factor (GCSF) for mobilization and CYC plus antithymocyte globulin for conditioning before the retransfusion of CD34 selected stem cells. The major outcome variable was the response to treatment [reduction of modified Rodnan skin score (mRSS) by 25%] at Month 6. Secondary endpoints were the transplant-related mortality and the progression-free survival.
Significant skin and lung function improvement of the mRSS was achieved in 78.3% of patients at Month 6. The overall response rate was 91%, as some patients improved even after Month 6. Three patients died between mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was considered treatment-related (i.e., GCSF or CYC toxicity). Depending on definitions, transplant-related mortality was 4% and treatment-related mortality 11%. Seven patients experienced a relapse during the 4.4 years of followup. The progression-free survival was 74%. Four patients died during followup and the most frequent causes of death were pulmonary and cardiac complications of SSc.
aSCT led to significant improvement in most patients with SSc. The procedure requires further optimization; hence we are modifying our screening and treatment strategy. To minimize infectious complications, CYC for mobilization and GCSF were reduced. We intensified our screening for cardiac involvement and modified our conditioning regimen in case of cardiac involvement.
自体干细胞移植（aSCT）治疗系统性硬化症（SSc）在最近的报道中已被证明是有效的。这种激进的方法和疾病本身与高死亡率相关。我们报告了 26 例连续患者的经验。
在 1997 年至 2009 年期间，26 例患者被安排进行 aSCT。我们的标准移植方案包括环磷酰胺（CYC）和粒细胞集落刺激因子（GCSF）用于动员，以及在回输 CD34 选择的干细胞之前用 CYC 和抗胸腺细胞球蛋白进行调理。主要结局变量是治疗[改良 Rodnan 皮肤评分（mRSS）降低 25%]在第 6 个月的反应。次要终点是与移植相关的死亡率和无进展生存率。
78.3%的患者在第 6 个月时皮肤和肺功能显著改善 mRSS。整体反应率为 91%，因为有些患者甚至在第 6 个月后仍有改善。3 例患者在动员和调理治疗期间死亡，2 例因严重疾病进展，1 例死亡被认为与治疗相关（即 GCSF 或 CYC 毒性）。根据定义，与移植相关的死亡率为 4%，治疗相关的死亡率为 11%。7 例患者在 4.4 年的随访期间复发。无进展生存率为 74%。4 例患者在随访期间死亡，最常见的死亡原因是 SSc 的肺部和心脏并发症。
aSCT 导致大多数 SSc 患者显著改善。该程序需要进一步优化；因此，我们正在修改我们的筛选和治疗策略。为了尽量减少感染并发症，我们减少了用于动员的 CYC 和 GCSF。我们加强了对心脏受累的筛查，并在有心脏受累的情况下修改了调理方案。
