Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma
Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma
复制标题
DOI：
10.1056/nejmoa1703327
复制
发表时间：
2018-01-04
影响因子：
158.5
通讯作者：
Furst, D. E.
中科院分区：
文献类型：
--
作者：
Sullivan, K. M.;Goldmuntz, E. A.;Furst, D. E.
背景技术尽管目前有治疗方法，但弥漫性皮肤系统性硬化症（硬皮病）常常具有毁灭性的后果。我们将清髓性 CD34+ 选择性自体造血干细胞移植与通过每月 12 个月输注环磷酰胺的方式对硬皮病患者进行免疫抑制进行了比较。方法我们将患有严重硬皮病的成人（18 至 69 岁）随机分配接受清髓性自体干细胞移植（36 名受试者）或接受环磷酰胺（39 名受试者）。主要终点是根据 54 个月时评估的疾病特征层次对参与者进行相互比较的全球排名综合评分：死亡、无事件生存（无呼吸、肾或心力衰竭的生存）、用力肺活量、健康评估问卷残疾指数评分以及改良的 Rodnan 皮肤评分。 结果在意向治疗人群中，54 个月时的全球排名综合评分显示移植的优越性（1404 例配对中的 67%）比较中赞成移植，33% 赞成环磷酰胺，P = 0.01）。在符合方案的人群（接受移植或完成≥9剂环磷酰胺的参与者）中，移植组54个月时的无事件生存率为79%，环磷酰胺组为50%（P = 0.02）。 72 个月时，Kaplan-Meier 对无事件生存率（74% 对 47%）和总生存率（86% 对 51%）的估计也有利于移植（P 分别 = 0.03 和 0.02）。移植组共有 9% 的参与者在 54 个月内开始使用缓解病情抗风湿药物 (DMARD)，而环磷酰胺组的这一比例为 44% (P = 0.001)。移植组的治疗相关死亡率在 54 个月时为 3%，在 72 个月时为 6%，而环磷酰胺组为 0%。结论清髓性自体造血干细胞移植在硬皮病患者中取得了长期益处，包括改善无事件生存率和总生存率，但代价是预期毒性增加。与治疗相关的死亡率和移植后 DMARD 的使用率低于以前的非清髓性移植报告。 （由美国国家过敏和传染病研究所和美国国立卫生研究院资助；ClinicalTrials.gov 编号，NCT00114530。）
BACKGROUNDDespite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma.METHODSWe randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.RESULTSIn the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P = 0.01). In the per-protocol population (participants who received a transplant or completed >= 9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P = 0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P = 0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P = 0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group.CONCLUSIONSMyeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials. gov number, NCT00114530.)