慢性髓性白血病治疗的现状。

Current perspectives for the treatment of chronic myeloid leukemia.

出版信息

Turk J Med Sci. 2019 Feb 11;49(1):1-10. doi: 10.3906/sag-1810-81.

Abstract

With an annual incidence of 1-2 in a million, Ph*(+) chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disease that makes myeloid neoplastic cells breed out of control. This BCR-ABL(+) myeloproliferative disease makes up about 15%-20% of all leukemia cases in adults. CML is seen more in males than females, with a rate of three to two. However, it does not show differences in prevalence in terms of age. CML consists of three clinical phases. The first one is the chronic phase, defined by rising white blood cell levels and also by myeloid proliferation and bone marrow maturation. While this phase does not exhibit complications, in diagnosis, it comprises most of the patients. The second phase is the accelerated phase, which the disease progresses to if it is not treated or does not respond to treatment. This usually takes about 3 years. The third phase is the blastic phase. The chronic phase can still progress to the next two phases within the first 2 years, with a rate of 10%. In the following years, the possibility increases by 15%-20% each year. Tyrosine kinase inhibitors (TKIs) are revolutionary drugs for the management of disease course in CML. The aim of this review is to assess current approaches to CML patients' follow-up and treatment with TKIs. A literature search on CML and TKIs was made in PubMed, Web of Science, and Scopus with particular focus on randomized clinical trials, recommendations, guidelines, and expert opinions. In managing CML, various treatment methods have been utilized for many decades. Prior to the development of TKIs, interferon alpha was the primary tool, which was then complemented by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT was successful in slowing the disease down in the long term and curing up to 50% of patients. Then the coming of the imatinib era opened up different treatment perspectives. For the patients resistant or intolerant to imatinib, second- and third-generation TKIs are successfully used in distinct CML disease states. The survival benefits of TKIs including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib for CML patients are outstanding. TKI-related adverse events could impact the clinical course, especially in long-term drug administrations. The current aim for CML disease management in the TKI era is to provide age- and sex-matched normal life duration to CML patients.

摘要

Ph*(+)慢性髓系白血病(CML)年发病率为 1-2/100 万,是一种克隆性造血干细胞疾病,导致髓系肿瘤细胞失控繁殖。这种 BCR-ABL(+)髓系增殖性疾病占成人所有白血病的 15%-20%。CML 多见于男性,男女比例为 3:2。然而,其在年龄方面并无明显差异。CML 包括三个临床阶段。第一个阶段是慢性期,表现为白细胞计数升高,以及髓系增殖和骨髓成熟。虽然此阶段无并发症,但在诊断时,它包含了大多数患者。第二个阶段是加速期,如果不治疗或治疗反应不佳,疾病会进展到这个阶段。通常需要大约 3 年。第三个阶段是急变期。慢性期在最初 2 年内仍可能进展到下两个阶段,发生率为 10%。在随后的几年中,每年的可能性增加 15%-20%。酪氨酸激酶抑制剂(TKI)是治疗 CML 疾病过程的革命性药物。本综述的目的是评估当前 CML 患者 TKI 随访和治疗的方法。在 PubMed、Web of Science 和 Scopus 上对 CML 和 TKI 进行了文献检索,特别关注随机临床试验、建议、指南和专家意见。在管理 CML 方面,几十年来一直使用各种治疗方法。在 TKI 开发之前,干扰素-α是主要的治疗方法,随后补充了异基因造血干细胞移植(HSCT)。HSCT 长期以来在减缓疾病方面取得了成功,并治愈了高达 50%的患者。然后,伊马替尼时代的到来开辟了不同的治疗视角。对于不耐受或耐药的患者,第二代和第三代 TKI 成功地应用于不同的 CML 疾病状态。TKI,包括伊马替尼、尼罗替尼、达沙替尼、博舒替尼和泊那替尼,对 CML 患者的生存获益显著。TKI 相关的不良反应可能会影响临床病程,尤其是在长期药物治疗中。在 TKI 时代,CML 疾病管理的当前目标是为 CML 患者提供与年龄和性别匹配的正常寿命。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/7350850/6e4b4bf66167/turkjmedsci-49-1-fig001.jpg

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