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甲磺酸伊马替尼治疗慢性粒细胞白血病的实践要点。

Practical aspects of the treatment of chronic myelogenous leukemia with imatinib mesylate.

作者信息

Zonder Jeffrey A, Schiffer Charles A

机构信息

Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Harper Hospital, 4 Brush South, 3990 John R, Detroit, MI 48201, USA.

出版信息

Curr Hematol Rep. 2003 Jan;2(1):57-64.

Abstract

Imatinib mesylate (Gleeve; formerly known as STI-571; Novartis Pharmaceuticals, Basel, Switzerland) is a protein tyrosine kinase inhibitor that has been approved by the US Food and Drug Administration for chronic-phase chronic myeloid leukemia (CML) that is refractory to or intolerant of interferon-alpha, and with accelerated and blast-phase CML. Imatinib is remarkably effective as treatment for chronic-phase and accelerated-phase CML at doses of 400 mg and 600 mg daily, respectively. Although dramatic responses are noted in patients with myeloid blast crisis, lymphoid blast crisis, and Philadelphia chromosome-positive acute lymphoblastic leukemia, the responses are usually incomplete and of short duration. The role of imatinib in relation to allogeneic stem cell transplantation is discussed, recognizing that the data on which any decisions can be made are relatively immature. At this time, it remains to be seen whether the chronic phase of CML can be extended sufficiently long in some patients so that they are functionally "cured," and whether doses of imatinib higher than 400 mg daily will improve response rates in chronic-phase CML. The feasibility of combining imatinib with other agents also needs to be examined, as does the utility of molecular monitoring of response. Finally, developing methods to overcome resistance to imatinib is a looming challenge.

摘要

甲磺酸伊马替尼(格列卫;曾用名STI-571;瑞士巴塞尔诺华制药公司)是一种蛋白酪氨酸激酶抑制剂,已获美国食品药品监督管理局批准,用于治疗对α干扰素难治或不耐受的慢性期慢性髓性白血病(CML),以及加速期和急变期CML。甲磺酸伊马替尼分别以每日400毫克和600毫克的剂量治疗慢性期和加速期CML时效果显著。尽管在髓系急变期、淋巴系急变期和费城染色体阳性急性淋巴细胞白血病患者中观察到显著反应,但这些反应通常不完全且持续时间短。文中讨论了甲磺酸伊马替尼在异基因干细胞移植中的作用,同时认识到可供做出任何决策的数据相对不成熟。目前,仍有待观察CML的慢性期在某些患者中是否能延长足够长的时间,从而使其在功能上“治愈”,以及每日高于400毫克的甲磺酸伊马替尼剂量是否会提高慢性期CML的缓解率。甲磺酸伊马替尼与其他药物联合使用的可行性以及反应分子监测的效用也需要进行研究。最后,开发克服对甲磺酸伊马替尼耐药的方法是一个迫在眉睫的挑战。

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