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[酪氨酸激酶抑制剂时代费城染色体阳性急性淋巴细胞白血病的治疗]

[Treatments for Philadelphia chromosome-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era].

作者信息

Dobashi Nobuaki

机构信息

Division of Clinical Oncology/Hematology, The Jikei University Daisan Hospital.

出版信息

Rinsho Ketsueki. 2020;61(9):1227-1235. doi: 10.11406/rinketsu.61.1227.

Abstract

The introduction of imatinib (IM) has led to a paradigm shift in the treatment strategy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). After introducing IM, second- and third-generation tyrosine kinase inhibitors (TKIs), which have stronger BCR-ABL1 inhibitory activity than IM, have appeared and their therapeutic results are beginning to be reported. However, to date, no comparison study between individual TKI and the current treatment strategy for Ph + ALL has been performed considering either a TKI-based regimen in induction followed by combination chemotherapy with a TKI or allogeneic hematopoietic stem cell transplantation (alloSCT). In the case of treating with ponatinib, it was suggested that the inclusion of alloSCT into the treatment strategy could be avoided. Because alloSCT has an appreciable treatment-related mortality rate and an upper age limit, the treatment strategy without alloSCT may remain mainstream in the future. Chemotherapy-free treatments, such as a TKI plus a monoclonal antibody or immunotherapy, are also expected to gain traction an alternate strategy and are now under investigation.

摘要

伊马替尼(IM)的引入使费城染色体阳性急性淋巴细胞白血病(Ph+ALL)的治疗策略发生了范式转变。引入IM后,出现了第二代和第三代酪氨酸激酶抑制剂(TKI),它们对BCR-ABL1的抑制活性比IM更强,其治疗结果也开始得到报道。然而,迄今为止,尚未进行过关于个体TKI与当前Ph+ALL治疗策略之间的比较研究,该研究未考虑诱导期基于TKI的方案,随后联合TKI化疗或异基因造血干细胞移植(alloSCT)。在用波纳替尼治疗的情况下,有人提出可以避免在治疗策略中纳入alloSCT。由于alloSCT有相当可观的治疗相关死亡率和年龄上限,未来不进行alloSCT的治疗策略可能仍将是主流。无化疗治疗,如TKI加单克隆抗体或免疫疗法,也有望成为一种替代策略并获得关注,目前正在研究中。

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