Drexler Beatrice, Passweg Jakob
Division of Hematology, University Hospital Basel, Petersgraben 4, Basel, 4031, Switzerland.
Division of Hematology, University Hospital Basel, Basel, Switzerland.
Ther Adv Hematol. 2021 Mar 3;12:2040620721998126. doi: 10.1177/2040620721998126. eCollection 2021.
Acquired aplastic anemia (AA) is characterized by a reduced stem cell reserve. Several preclinical studies have confirmed the beneficial effect of thrombopoietin (TPO) on the expansion and maintenance of hematopoietic stem cells (HSCs). Thus, TPO receptor agonists seem to be an ideal therapeutic agent for AA to augment marrow function. First studies with eltrombopag as a single agent at 150 mg/day showed an overall response rate of 40-50% in patients with refractory severe AA (rSAA). Subsequent studies examined the first-line use of eltrombopag together with horse antithymocyte globulin and cyclosporine, reaching response rates up to 94%. Although used at high doses, known adverse events in the form of skin, gastrointestinal, or hepatic impairment are feasible in AA, however first data show a relatively high rate of clonal evolution in the form of karyotypic aberrations in patients with rAA. Nonetheless, there is a strong rationale that eltrombopag can contribute to restoring hematopoiesis in SAA by stimulating HSCs. Further studies are needed to decide if eltrombopag is clearly superior to current established treatments and to determine optimal treatment duration, dosage, and long-term effects.
获得性再生障碍性贫血（AA）的特征是干细胞储备减少。多项临床前研究已证实血小板生成素（TPO）对造血干细胞（HSC）的扩增和维持具有有益作用。因此，TPO受体激动剂似乎是增强骨髓功能治疗AA的理想药物。最初以每日150毫克的剂量单独使用艾曲泊帕进行的研究显示，难治性重型AA（rSAA）患者的总体缓解率为40%-50%。随后的研究探讨了艾曲泊帕与马抗胸腺细胞球蛋白和环孢素联合用于一线治疗的效果，缓解率高达94%。尽管使用的是高剂量，但在AA患者中，以皮肤、胃肠道或肝脏损害形式出现的已知不良事件是可能发生的，不过初步数据显示，rAA患者中以核型异常形式出现的克隆进化发生率相对较高。尽管如此，有充分的理由认为艾曲泊帕可通过刺激HSC来促进SAA患者的造血恢复。需要进一步研究来确定艾曲泊帕是否明显优于目前已确立的治疗方法，并确定最佳治疗持续时间、剂量和长期效果。
