Division of Hematology, Hospital A Beneficência Portuguesa, Sao Paulo, Brazil.
Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):450-456. doi: 10.1182/asheducation-2018.1.450.
Since the approval of horse antithymocyte globulin (ATG) decades ago, there was a long hiatus in therapies with activity in severe aplastic anemia (SAA). This scenario changed in 2014 when eltrombopag, a thrombopoietin receptor agonist, was approved for SAA after an insufficient response to initial immunosuppressive therapy (IST). The basis for this approval was the observation of single-agent activity of eltrombopag in this patient population, where 40% to 50% recovered blood counts at times involving >1 lineage. The achievement of transfusion independence confirmed the clinical benefit of this approach. Increase in marrow cellularity and CD34+ cells suggested a recovery to a more functioning bone marrow. Further in its development, eltrombopag was associated with standard horse ATG plus cyclosporine in first line, producing increases in overall (at about 90%) and complete response rates (at about 40%) and leading to transfusion independence and excellent survival. Interestingly, best results were observed when all drugs were started simultaneously. The cumulative incidence of clonal cytogenetic abnormalities to date has compared favorably with the vast experience with IST alone in SAA. Longer follow-up will help in define these long-term risks. In this review, the development of eltrombopag in SAA will be discussed.
自从几十年前批准马抗胸腺细胞球蛋白（ATG）以来，在严重再生障碍性贫血（SAA）的治疗中，其活性有很长一段时间没有得到应用。这种情况在 2014 年发生了变化，当时血小板生成素受体激动剂艾曲波帕在初始免疫抑制治疗（IST）反应不足的情况下被批准用于 SAA。这种批准的依据是观察到艾曲波帕在这种患者人群中的单一药物活性，其中 40%至 50%的患者在涉及> 1 系的情况下恢复了血细胞计数。输血独立性的获得证实了这种方法的临床益处。骨髓细胞增多和 CD34+细胞的增加表明骨髓恢复到更具功能的状态。在其进一步发展中，艾曲波帕与标准马 ATG 加环孢素联合用于一线治疗，总体反应率（约 90%）和完全反应率（约 40%）增加，并导致输血独立性和良好的生存。有趣的是，当所有药物同时开始使用时，观察到最佳结果。迄今为止，克隆细胞遗传学异常的累积发生率与 SAA 中单独使用 IST 的大量经验相比具有优势。更长时间的随访将有助于确定这些长期风险。在这篇综述中，将讨论艾曲波帕在 SAA 中的发展情况。
