Kuter David J, Begley C Glenn
Hematology/Oncology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Blood. 2002 Nov 15;100(10):3457-69. doi: 10.1182/blood.V100.10.3457.
Thrombocytopenia is a common medical problem for which the main treatment is platelet transfusion. Given the increasing use of platelets and the declining donor population, identification of a safe and effective platelet growth factor could improve the management of thrombocytopenia. Thrombopoietin (TPO), the c-Mpl ligand, is the primary physiologic regulator of megakaryocyte and platelet development. Since the purification of TPO in 1994, 2 recombinant forms of the c-Mpl ligand--recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF)--have undergone extensive clinical investigation. Both have been shown to be potent stimulators of megakaryocyte growth and platelet production and are biologically active in reducing the thrombocytopenia of nonmyeloablative chemotherapy. However, neither TPO has demonstrated benefit in stem cell transplantation or leukemia chemotherapy. Other clinical studies have investigated the use of TPO in treating chronic nonchemotherapy-induced thrombocytopenia associated with myelodysplastic syndromes, idiopathic thrombocytopenic purpura, thrombocytopenia due to human immunodeficiency virus, and liver disease. Based solely on animal studies, TPO may be effective in reducing surgical thrombocytopenia and bleeding, ex vivo expansion of pluripotent stem cells, and as a radioprotectant. Ongoing and future studies will help define the clinical role of recombinant TPO and TPO mimetics in the treatment of chemotherapy- and nonchemotherapy-induced thrombocytopenia.
血小板减少症是一种常见的医学问题，其主要治疗方法是血小板输注。鉴于血小板使用量的增加和献血人群的减少，确定一种安全有效的血小板生长因子可改善血小板减少症的治疗。血小板生成素（TPO），即c-Mpl配体，是巨核细胞和血小板生成的主要生理调节因子。自1994年TPO纯化以来，c-Mpl配体的两种重组形式——重组人血小板生成素（rhTPO）和聚乙二醇化重组人巨核细胞生长和发育因子（PEG-rHuMGDF）——已进行了广泛的临床研究。两者均已被证明是巨核细胞生长和血小板生成的有效刺激剂，并且在减轻非清髓性化疗引起的血小板减少症方面具有生物活性。然而，这两种TPO在干细胞移植或白血病化疗中均未显示出益处。其他临床研究调查了TPO在治疗与骨髓增生异常综合征、特发性血小板减少性紫癜、人类免疫缺陷病毒引起的血小板减少症以及肝病相关的慢性非化疗诱导的血小板减少症中的应用。仅基于动物研究，TPO可能在减少手术引起的血小板减少症和出血、多能干细胞的体外扩增以及作为辐射防护剂方面有效。正在进行的和未来的研究将有助于确定重组TPO和TPO模拟物在治疗化疗和非化疗诱导的血小板减少症中的临床作用。
