Tijssen Marloes R, van der Schoot C Ellen, Voermans Carlijn, Zwaginga Jaap Jan
Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.
Transfus Med Rev. 2006 Oct;20(4):283-93. doi: 10.1016/j.tmrv.2006.05.003.
High-dose chemotherapy followed by a peripheral blood stem cell transplant is successfully used for a wide variety of malignancies. A major drawback, however, is the delay in platelet recovery. Several clinical strategies using thrombopoietin (Tpo) have been developed in an attempt to speed up platelet repopulation. In contrast to its success in immune thrombocytopenia and in low-dose toxic chemotherapeutic regimens, Tpo appears less effective in the case of high-dose chemotherapy and peripheral blood stem cell transplant. To develop a successful therapeutic approach, more knowledge is needed on several aspects of megakaryocyte (progenitor) biology, such as homing to the bone marrow, endomitosis, and platelet formation. Interactions of the megakaryocytes with the marrow vasculature and the microvascular microenvironment are other key factors for optimal thrombocytopoiesis. The present report reviews the background of the inefficiency of Tpo after intensive chemotherapy and describes possible strategies that might lead to successful therapies to treat chemotherapy-induced thrombocytopenia.
大剂量化疗后进行外周血干细胞移植已成功应用于多种恶性肿瘤。然而,一个主要缺点是血小板恢复延迟。已经开发了几种使用血小板生成素(Tpo)的临床策略,试图加速血小板再生。与在免疫性血小板减少症和低剂量毒性化疗方案中的成功相比,Tpo在大剂量化疗和外周血干细胞移植的情况下似乎效果较差。为了开发一种成功的治疗方法,需要更多关于巨核细胞(祖细胞)生物学几个方面的知识,例如归巢到骨髓、核内有丝分裂和血小板形成。巨核细胞与骨髓脉管系统和微血管微环境的相互作用是最佳血小板生成的其他关键因素。本报告回顾了强化化疗后Tpo无效的背景,并描述了可能导致成功治疗化疗诱导的血小板减少症的策略。