Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug
Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug
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DOI：
10.1182/blood-2013-10-534743
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发表时间：
2014-03-20
期刊：
影响因子：
20.3
通讯作者：
Dunbar, Cynthia E.
中科院分区：
文献类型：
--
作者：
Desmond, Ronan;Townsley, Danielle M.;Dunbar, Cynthia E.
尽管接受了免疫抑制治疗，但约四分之一的严重再生障碍性贫血患者仍然存在全血细胞减少症。我们之前已经证明艾曲波帕在这种情况下有效，44%（11/25）的患者出现临床上显着的血液学反应。我们现在报告另外 18 名患者的安全性和有效性数据，以及对整个队列 43 名患者的长期随访。 3 至 4 个月时，43 名患者中有 17 名患者有总缓解率 (40%)，包括三系和双系缓解。在一项扩展研究中，大多数仍使用艾曲波帕的患者 (14/17) 继续表现出改善，其中 7 名患者的中性粒细胞、红细胞和血小板谱系最终显着增加。 5 名血细胞计数接近正常化的患者在入组后中位 28.5 个月（范围为 9-37 个月）时停药，并且在艾曲波帕治疗后中位 13 个月（范围为 1-15 个月）内血细胞计数均保持稳定。 8 名患者，包括 6 名无反应者和 2 名反应者，在艾曲波帕治疗后出现了新的细胞遗传学异常，其中 5 名患者出现 7 号染色体丢失或部分缺失。迄今为止，没有人进化为急性髓系白血病。艾曲波帕对免疫抑制治疗难治的再生障碍性贫血患者有效，这些患者具有频繁的多谱系反应并在治疗后维持正常化的造血功能。这项研究在 www.clinicaltrials.gov 上注册为#NCT00922883。
About a quarter of patients with severe aplastic anemia remain pancytopenic despite immunosuppressive therapy. We have previously demonstrated that eltrombopag has efficacy in this setting with 44%(11/25) of patients having clinically significant hematologic responses. We now report safety and efficacy data on a further 18 patients and long-term follow-up on the entire cohort of 43 patients. The overall response rate was 17 of 43 patients (40%) at 3 to 4 months, including tri- and bilineage responses. The majority of patients who remained on eltrombopag in an extension study (14/17) continued to show improvement, and 7 eventually had significant increases in neutrophil, red cell, and platelet lineages. Five patients with robust near-normalization of blood counts had drug discontinued at a median of 28.5 months after entry (range, 9-37 months), and all maintained stable counts a median of 13 months (range, 1-15 months) off eltrombopag. Eight patients, including 6 nonresponders and 2 responders, developed new cytogenetic abnormalities on eltrombopag, including 5 with chromosome 7 loss or partial deletion. None evolved to acute myeloid leukemia to date. Eltrombopag is efficacious in a subset of patients with aplastic anemia refractory to immunosuppressive therapy, with frequent multilineage responses and maintenance of normalized hematopoiesis off treatment. This study is registered at www.clinicaltrials.gov as #NCT00922883.