Hematopoietic stem cell transplantation for systemic sclerosis: Brazilian experience
Hematopoietic stem cell transplantation for systemic sclerosis: Brazilian experience
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DOI：
10.1186/s42358-021-00166-8
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发表时间：
2021-01-01
影响因子：
2.3
通讯作者：
Oliveira, Maria Carolina
中科院分区：
文献类型：
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作者：
Henrique-Neto, Álvaro;Vasconcelos, Marianna Yumi Kawashima;Oliveira, Maria Carolina
背景近20年来，造血干细胞移植(HSCT)作为治疗系统性硬化症(SSC)的手段被广泛研究。HSCT的目标是根除自身反应性免疫系统，取而代之的是一种新的免疫系统，具有长期调节和对自身抗原的耐受性。在这里，我们描述了在巴西一个中心接受HSCT的严重和难治性SSc患者的临床结果。患者和方法这是一项纵向的回顾研究，包括从2009年到2016年间接受自体造血干细胞移植的70名确诊为SSc的成年SSC患者。该程序包括采集和冷冻保存自体造血祖细胞，然后给药免疫消融方案，然后输注先前收集的细胞。患者在移植前、移植后6个月和每年进行评估，直到移植后至少5年的随访。在每个评估时间点，患者都要接受临床检查，包括改良罗德南皮肤评分(MRSS)评估、超声心动图、高分辨率肺CT和肺功能。结果年龄中位数为35.9岁(19~59岁)，女性57例(81.4%)，非雷诺病病程中位数为2年(1~7年)。移植前96%的患者有弥漫性皮肤受累，84.2%有间质性肺疾病，67%有抗拓扑异构酶I抗体阳性。皮肤受累程度显著改善，移植后所有时间点的MRSS都有所下降，直到至少5年的随访。分析HSCT前间质性肺疾病患者的肺功能(用力肺活量和肺一氧化碳弥散量)在5年的随访期内均有改善。移植后8年的总存活率为81%，无进展存活率为70.5%。3名患者死于移植相关毒性，9名患者因疾病复发在随访期间死亡，1名患者死于血栓性血小板减少性紫癜。结论自体造血祖细胞移植可改善皮肤和间质肺损害。这些结果符合国际经验，支持HSCT作为严重和进行性系统性硬化症患者的一种可行的治疗选择。
Background In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. Patients and methods This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan's skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. Results Median (range) age was 35.9 (19-59), with 57 (81.4%) female and median (range) non-Raynaud's disease duration of 2 (1-7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. Conclusions Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.