National Heart, Lung, and Blood Institutes, National Institutes of Health, Bethesda, MD.
AstraZeneca, Gaithersburg, MD.
Semin Hematol. 2022 Jan;59(1):21-29. doi: 10.1053/j.seminhematol.2022.01.002. Epub 2022 Jan 19.
Severe aplastic anemia, a disease characterized by pancytopenia and a hypocellular marrow, is treatable by either immunosuppressive therapy (IST) or hematopoietic stem cell transplant. Much is understood about the immune-mediated pathophysiology of AA now, but the inciting factor remains elusive. Many groups around the globe contributed to understanding the disease pathophysiology and optimizing the IST regimen. Horse antithymocyte globulin and cyclosporine, the initial IST regimen, achieved a hematologic response rate in about 60% to 65% of treated patients, with less than 10% achieving a complete count recovery. However, adding a thrombopoietin receptor agonist, eltrombopag (EPAG), to IST improved these response rates to nearly 80% and an unprecedented increase in complete response to almost 40%. The latest report indicates that a high-risk clonal evolution to myeloid malignancies is not increased with hematopoietic stem cell stimulation by adding EPAG in the front line setting. Despite the great success of IST and EPAG in improving early outcomes, relapse remains a problem. Further optimization of upfront therapy and treatment protocol is needed to prevent relapses and decrease clonal evolution rates for even better long-term results.
严重再生障碍性贫血（aplastic anemia，AA）是一种以全血细胞减少和骨髓细胞减少为特征的疾病，可通过免疫抑制治疗（immunosuppressive therapy，IST）或造血干细胞移植来治疗。目前，人们对 AA 的免疫介导的病理生理学有了很多了解，但致病因素仍不清楚。全球许多团体为了解疾病的病理生理学和优化 IST 方案做出了贡献。马抗胸腺细胞球蛋白和环孢素是最初的 IST 方案，在接受治疗的患者中，约有 60%至 65%达到血液学反应，不到 10%达到完全计数恢复。然而，在 IST 中添加血小板生成素受体激动剂（thrombopoietin receptor agonist，EPAG）可将这些反应率提高到近 80%，并使完全缓解率前所未有地提高到近 40%。最新报告表明，在前线治疗中添加 EPAG 刺激造血干细胞不会增加髓系恶性肿瘤的高危克隆进化。尽管 IST 和 EPAG 在改善早期结果方面取得了巨大成功，但复发仍然是一个问题。需要进一步优化一线治疗和治疗方案，以防止复发和降低克隆进化率，从而获得更好的长期结果。
