Use of Eculizumab in Patients With Allogeneic Stem Cell Transplant-Associated Thrombotic Microangiopathy: A Study From the SFGM-TC
Use of Eculizumab in Patients With Allogeneic Stem Cell Transplant-Associated Thrombotic Microangiopathy: A Study From the SFGM-TC
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DOI：
10.1097/tp.0000000000000601
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发表时间：
2015-09-01
期刊：
影响因子：
6.2
通讯作者：
de Latour, Regis Peffaut
中科院分区：
文献类型：
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作者：
de Fontbrune, Flore Sicre;Galambrun, Claire;de Latour, Regis Peffaut
背景资料。异基因造血干细胞移植(HSCT)后发生的血栓性微血管病(TMA)具有毁灭性的预后。目前的治疗(主要是血浆置换)的应答率并不令人满意。异基因造血干细胞移植后血栓性微血管病变与非典型溶血性尿毒症综合征(AHUS)在潜在的发病机制上有相似之处。Eculizumab在aHUS中取得了令人印象深刻的结果。材料和方法我们回顾分析了2010至2013年间在法国接受Eculizumab治疗的12名HSCT后严重TMA患者。结果。所有12例患者均有严重的TMA伴神经和/或肾脏受累。58%的患者对一线血浆置换无效。在TMA诊断时，50%的患者有感染，33%的患者有急性移植物抗宿主病。根据aHUS治疗方案，患者接受Eculizumab治疗。中位随访时间14个月，血液学反应率和总存活率分别为50%和33%。在诊断为移植物抗宿主病时，活动性急性移植物抗宿主病是唯一与总体存活率较差相关的因素(P=0.009)。讨论。在我们的队列中，Eculizumab的应答率和总存活率与之前在TMA上发表的异基因造血干细胞移植后的数据相比是有利的。为了证实这些结果，有必要进行前瞻性试验。早期应用Eculizumab可能对远期肾功能有有利影响，进而有助于延长生存期。
Background. Thrombotic microangiopathy (TMA) occurring after allogeneic hematopoietic stem cell transplantation (HSCT) has a devastating prognosis. Response rates to current therapies (mainly plasma exchange) are unsatisfactory. Thrombotic microangiopathy after allogeneic HSCT shares similarities with atypical hemolytic uremic syndrome (aHUS) in the underlying pathomechanisms. Eculizumab has been associated with impressive results in aHUS. Materials and Methods. We retrospectively analyzed 12 patients who received Eculizumab in France between 2010 and 2013 for severe post-HSCT TMA. Results. All 12 patients had severe TMA with neurological and/or renal involvement. Fifty-eight percent were refractory to first-line plasma exchange. At the time of TMA diagnosis, infections were present in 50% of the patients and acute graft-versus-host disease in 33%. Patients were treated with Eculizumab according to the aHUS therapeutic scheme. With a median follow-up of 14 months, hematological response and overall survival were 50% and 33%, respectively. Active acute graft versus-host disease at TMA diagnosis was the only factor associated with worse overall survival (P = 0.009). Discussion. Response rate and overall survival after Eculizumab in our cohort compare favorably with previously published data in TMA after allogeneic HSCT. Prospective trials are warranted to confirm these results. Early initiation of Eculizumab may have a favorable effect on long-term renal function and further contribute to the prolongation of survival.