依库珠单抗在异基因干细胞移植相关血栓性微血管病患者中的应用：来自SFGM-TC的一项研究
Use of Eculizumab in Patients With Allogeneic Stem Cell Transplant-Associated Thrombotic Microangiopathy: A Study From the SFGM-TC.
作者信息
de Fontbrune Flore Sicre, Galambrun Claire, Sirvent Anne, Huynh Anne, Faguer Stanislas, Nguyen Stephanie, Bay Jacques-Olivier, Neven Bénédicte, Moussi Julie, Simon Laurence, Xhaard Alienor, Resche-Riggon Matthieu, O'Meara Alix, Fremeaux-Bacchi Veronique, Veyradier Agnes, Socié Gérard, Coppo Paul, de Latour Régis Peffaut
机构信息
1 Hématologie Greffe de Moelle, Hôpital Saint Louis, APHP, Université Paris Diderot, Paris, France. 2 Service d'Hématologie Pédiatrique, Hôpital de la Timone, Marseille, France. 3 Service d'Onco-hematologie Pédiatrique, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire de Montpellier, Montpellier, France. 4 Service d'Hématologie, CHU de Purpan, Toulouse, France. 5 Département de Néphrologie et Transplantation d'organe, CHU de Rangueil, Toulouse, France. 6 Service d'Hématologie, Hôpital de la Pitié Salpetrière, APHP, Université Pierre et Marie Curie, Paris. 7 Service de Thérapie Cellulaire et d'Hématologie Clinique, Hôpital d'Estaing, CHU Clermont Ferrand, Université d'Auvergne, Clermont-Ferrand, France. 8 Service d'Immuno-hématologie et Rhumatologie pédiatrique, Hôpital Necker-Enfants Malades, Laboratoire INSERM U768, Institut Imagine, Université Sorbonne Paris-cité, Paris, France. 9 Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, APHM, Université d'Aix Marseille, Marseille, France. 10 Service d'Hématologie, Hôpital Hautepierre, Hôpitaux Universitaire de Strasbourg, Strasbourg, France. 11 Département de Biostatistiques, Hôpital Saint Louis, APHP, Université Paris Diderot, Paris, France. 12 Service d'Immunologie Biologique, Hôpital Européen George Pompidou, APHP, CHU Paris Ouest, Paris, France. 13 Service d'Hématologie Biologique, Hôpital Antoine Beclère, APHP, Université Paris Sud, Clamart, France. 14 Service d'Hématologie, Centre de Référence des Microangiopathies Thrombotiques, Hôpitaux Universitaires de l'Est Parisien, APHP, Université Pierre et Marie Curie, Paris, France.
出版信息
Transplantation. 2015 Sep;99(9):1953-9. doi: 10.1097/TP.0000000000000601.
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.
背景
异基因造血干细胞移植（HSCT）后发生的血栓性微血管病（TMA）预后极差。目前治疗方法（主要是血浆置换）的缓解率并不理想。异基因HSCT后的血栓性微血管病在潜在发病机制上与非典型溶血性尿毒症综合征（aHUS）有相似之处。依库珠单抗治疗aHUS已取得显著疗效。
材料与方法
我们回顾性分析了2010年至2013年期间在法国接受依库珠单抗治疗严重HSCT后TMA的12例患者。
结果
所有12例患者均患有严重TMA，伴有神经和/或肾脏受累。58%的患者对一线血浆置换治疗无效。在TMA诊断时，50%的患者存在感染，33%的患者存在急性移植物抗宿主病。患者按照aHUS治疗方案接受依库珠单抗治疗。中位随访14个月时，血液学缓解率和总生存率分别为50%和33%。TMA诊断时存在活跃的急性移植物抗宿主病是与较差总生存率相关的唯一因素（P = 0.009）。
讨论
我们队列中依库珠单抗治疗后的缓解率和总生存率与先前发表的异基因HSCT后TMA的数据相比更具优势。有必要进行前瞻性试验以证实这些结果。早期开始使用依库珠单抗可能对长期肾功能有有利影响，并进一步有助于延长生存期。
Zotero 插件