Eltrombopag and improved hematopoiesis in refractory aplastic anemia.
Eltrombopag and improved hematopoiesis in refractory aplastic anemia.
复制标题
艾曲波帕和改善难治性再生障碍性贫血的造血功能。
DOI：
10.1056/nejmoa1200931
复制
发表时间：
2012-07-05
期刊：
影响因子：
--
通讯作者：
Dunbar CE
中科院分区：
文献类型：
--
作者：
Olnes MJ;Scheinberg P;Calvo KR;Desmond R;Tang Y;Dumitriu B;Parikh AR;Soto S;Biancotto A;Feng X;Lozier J;Wu CO;Young NS;Dunbar CE
重型再生障碍性贫血以免疫介导的骨髓发育不良和全血细胞减少为特征，免疫抑制治疗或同种异体移植可有效治疗。三分之一的患者患有免疫抑制难治性疾病，伴有持续严重的血细胞减少和造血干细胞和祖细胞严重缺陷。血小板生成素可增加造血干细胞和祖细胞的数量。我们进行了一项II期研究，涉及免疫抑制难治性再生障碍性贫血患者，以确定口服血小板生成素模拟物艾曲泊帕（Promacta）是否可以改善血细胞计数。25例患者接受艾曲泊帕50 mg剂量，可根据需要增加至最大剂量150 mg/天，共12周。主要终点是血细胞计数或输血独立性的临床显著变化。缓解患者继续接受艾曲泊帕治疗。25例患者中有11例（44%）在12周时至少在一个谱系中有血液学应答，毒性作用极小。9名患者不再需要血小板输注（血小板计数中位数增加，每立方毫米44，000）。6名患者的血红蛋白水平有所改善（平均增加4.4 g/dl）;其中3名患者以前依赖于红细胞输注，不再需要输血。9例患者中性粒细胞计数增加（中位数增加，每立方毫米1350）。连续骨髓活检显示，有反应的患者的三系造血正常化，没有增加纤维化。免疫功能监测显示无一致变化。艾曲泊帕治疗与某些难治性重度再生障碍性贫血患者的多系临床应答相关。（由国家心肺血液研究所资助; ClinicalTrials.gov编号，NCT 00922883。
Severe aplastic anemia, which is characterized by immune-mediated bone marrow hypoplasia and pancytopenia, can be treated effectively with immunosuppressive therapy or allogeneic transplantation. One third of patients have disease that is refractory to immunosuppression, with persistent, severe cytopenia and a profound deficit in hematopoietic stem cells and progenitor cells. Thrombopoietin may increase the number of hematopoietic stem cells and progenitor cells. We conducted a phase 2 study involving patients with aplastic anemia that was refractory to immunosuppression to determine whether the oral thrombopoietin mimetic eltrombopag (Promacta) can improve blood counts. Twenty-five patients received eltrombopag at a dose of 50 mg, which could be increased, as needed, to a maximum dose of 150 mg daily, for a total of 12 weeks. Primary end points were clinically significant changes in blood counts or transfusion independence. Patients with a response continued to receive eltrombopag. Eleven of 25 patients (44%) had a hematologic response in at least one lineage at 12 weeks, with minimal toxic effects. Nine patients no longer needed platelet transfusions (median increase in platelet count, 44,000 per cubic millimeter). Six patients had improved hemoglobin levels (median increase, 4.4 g per deciliter); 3 of them were previously dependent on red-cell transfusions and no longer needed transfusions. Nine patients had increased neutrophil counts (median increase, 1350 per cubic millimeter). Serial bone marrow biopsies showed normalization of trilineage hematopoiesis in patients who had a response, without increased fibrosis. Monitoring of immune function revealed no consistent changes. Treatment with eltrombopag was associated with multilineage clinical responses in some patients with refractory severe aplastic anemia. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00922883.)