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维奈托克联合地西他滨治疗复发 T 细胞急性淋巴细胞白血病:病例报告及文献复习。

Venetoclax and decitabine for treatment of relapsed T-cell acute lymphoblastic leukemia: A case report and review of literature.

机构信息

Department of Medicine, Division of Hematology and Oncology, University of Florida, Gainesville, FL, USA.

Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.

出版信息

Hematol Oncol Stem Cell Ther. 2021 Sep;14(3):246-251. doi: 10.1016/j.hemonc.2019.10.002. Epub 2020 Mar 19.

Abstract

Despite improvements in first-line treatment of T-cell acute lymphoblastic leukemia (T-ALL), the outcome of relapsed T-ALL remains dismal with less than 7% achieving a long-term survival. Thus, there is an unmet need for new treatment strategies to improve outcomes in this setting. Suppression of apoptosis is one of the hallmarks of anticancer drug resistance. Hence, over the past few years, antiapoptotic proteins have become an attractive target for therapeutic intervention in several hematologic malignancies. Venetoclax (ABT-199) is a novel, orally bioavailable small-molecule inhibitor of B-cell lymphoma 2 (BCL-2), a key regulator of the intrinsic apoptotic pathway. Recent preclinical studies have suggested that inhibition of BCL-2 may be a novel therapeutic strategy for patients with T-ALL. Herein, we report a case of clinical response to venetoclax in combination with a hypomethylating agent in a patient with relapsed T-ALL after allogeneic stem cell transplant and review the existing literature.

摘要

尽管 T 细胞急性淋巴细胞白血病 (T-ALL) 的一线治疗有所改善,但复发 T-ALL 的预后仍然很差,长期生存的不到 7%。因此,需要新的治疗策略来改善这种情况下的治疗效果。抑制细胞凋亡是抗癌药物耐药性的标志之一。因此,在过去几年中,抗凋亡蛋白已成为治疗几种血液系统恶性肿瘤的有吸引力的治疗靶点。Venetoclax(ABT-199)是一种新型、口服生物可利用的 B 细胞淋巴瘤 2(BCL-2)小分子抑制剂,是内在凋亡途径的关键调节剂。最近的临床前研究表明,抑制 BCL-2 可能是 T-ALL 患者的一种新的治疗策略。在此,我们报告了一例异基因干细胞移植后复发 T-ALL 患者联合使用 venetoclax 和去甲基化剂的临床反应,并回顾了现有文献。

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