Ikeda Y, Miyakawa Y
Division of Hematology, Keio University School of Medicine, Tokyo, Japan.
J Thromb Haemost. 2009 Jul;7 Suppl 1:239-44. doi: 10.1111/j.1538-7836.2009.03440.x.
Thrombopoietin (TPO) is an essential hematopoietic cytokine for megakaryopoiesis. In 2002, we demonstrated that pegylated-recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) increased platelet counts in patients with chronic immune thrombocytopenic purpura (ITP) in a Phase I/II clinical trial. After the cessation of clinical trials of PEG-rHuMGDF because of severe thrombocytopenia or pancytopenia due to the development of the neutralizing antibody cross-reacting with endogenous TPO, second generation non-immunogenic TPO receptor agonists have been developed. A small molecule eltrombopag and Romiplostim were approved for clinical use by FDA in 2008 to treat patients with chronic ITP who are refractory to the prior therapy. Although the efficacy of both TPO receptor agonists is convincing for the refractory ITP, further investigation is necessary to assess the potential long-term side effects and clinical applications of these therapies for other thrombocytopenic conditions.
血小板生成素（TPO）是巨核细胞生成所必需的造血细胞因子。2002年，我们在一项I/II期临床试验中证明，聚乙二醇化重组人巨核细胞生长和发育因子（PEG-rHuMGDF）可提高慢性免疫性血小板减少性紫癜（ITP）患者的血小板计数。由于出现与内源性TPO发生交叉反应的中和抗体，导致严重血小板减少或全血细胞减少，PEG-rHuMGDF的临床试验停止后，第二代无免疫原性的TPO受体激动剂已被开发出来。小分子艾曲泊帕和罗米司亭于2008年被美国食品药品监督管理局（FDA）批准用于临床，治疗对先前治疗无效的慢性ITP患者。尽管这两种TPO受体激动剂对难治性ITP的疗效令人信服，但仍需进一步研究，以评估这些疗法对其他血小板减少症的潜在长期副作用和临床应用。
