Service Hématologie Greffe, Centre de Référence Aplasies Médullaires Acquises et Constitutionnelles, Université Paris Diderot, Sorbonne Paris Cité, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France.
Service d'Hématologie Clinique, Centre de Compétence Aplasies Médullaires Acquises et Constitutionnelles, Hôpital Haut Lévêque, Bordeaux, France.
Am J Hematol. 2018 May;93(5):635-642. doi: 10.1002/ajh.25050. Epub 2018 Feb 14.
Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard immunosuppressive treatment (IST) for patients with aplastic anemia. A prospective randomized trial showed in 2011 that hATG was superior to rabbit ATG for first-line treatment of severe AA. The French Health Agency (ANSM) permitted a patient-named authorization for temporary use (ATU) program of hATG (ATGAM, Pfizer) in patients with AA in 2011 since commercial access to hATG is not approved. We took advantage of this program to analyze the outcomes of 465 patients who received antithymocyte globulins (ATGAM) plus CSA as first line treatment (n = 379; 81.5%), or for refractory (n = 26) or relapsed disease (n = 33), from September 2011 to March 2017. In the entire cohort one year, 72% of the patients had partial and 13% had complete response, with worse response for patients with severe AA and a longer interval between diagnosis and IST (more than 6 months). Severe adverse events were mainly linked to infections (24%), hemorrhages (6%), and elevated liver function tests (5%). Overall at 12 months, 9.7% of patients required second line IST and 15.6% received transplantation. Fifty-five patients died during the study mainly because of infections (53%). Factors predicting independently worse survival were age over 40 years, neutrophils less than 0.5 × 10 /L, male gender and longer delay between diagnosis and hATG (>6 months period). This study does illustrate the results of ATGAM with CSA in a true-life perspective and confirms ATGAM as standard of care IST to treat patients with AA not eligible for HSCT.
抗胸腺细胞球蛋白（ATG）加环孢素（CSA）是再生障碍性贫血患者的金标准免疫抑制治疗（IST）。2011 年的一项前瞻性随机试验表明，马抗胸腺细胞球蛋白（hATG）在治疗重型 AA 的一线治疗中优于兔抗胸腺细胞球蛋白。由于商业准入 hATG 未获批准，2011 年法国卫生署（ANSM）允许在患有 AA 的患者中进行 hATG（ATGAM，辉瑞）的患者命名授权临时使用（ATU）计划。我们利用该计划分析了 2011 年 9 月至 2017 年 3 月期间 465 名接受抗胸腺细胞球蛋白（ATGAM）加 CSA 作为一线治疗（n=379；81.5%）或难治性（n=26）或复发疾病（n=33）的患者的结果。在整个队列中，1 年内，72%的患者有部分反应，13%的患者有完全反应，对于重型 AA 患者和诊断与 IST 之间间隔时间较长（超过 6 个月）的患者，反应较差。严重不良事件主要与感染（24%）、出血（6%）和肝功能试验升高（5%）有关。总体而言，12 个月时，9.7%的患者需要二线 IST，15.6%的患者接受了移植。55 名患者在研究期间死亡，主要是因为感染（53%）。独立预测生存较差的因素是年龄超过 40 岁、中性粒细胞<0.5×10/L、男性和诊断与 hATG 之间的时间间隔延长（>6 个月）。本研究确实说明了 CSA 联合 ATGAM 在真实生活中的结果，并证实 ATGAM 是治疗不适合 HSCT 的 AA 患者的标准护理 IST。
