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成人急性 T 淋巴细胞白血病和髓系/T 淋巴细胞白血病的现代治疗方法:从现有标准到精准医学。

Modern treatment approaches to adult acute T-lymphoblastic and myeloid/T-lymphoblastic leukemia: from current standards to precision medicine.

机构信息

Hematology Unit, Azienda Ulss3 Serenissima, Ospedale dell'Angelo, Venezia-Mestre.

Department of Medicine and Surgery, University of Perugia, Perugia.

出版信息

Curr Opin Oncol. 2022 Nov 1;34(6):738-747. doi: 10.1097/CCO.0000000000000900. Epub 2022 Aug 26.

Abstract

PURPOSE OF REVIEW

To review the most recent advancements in the management of adult T-cell acute lymphoblastic leukemia (T-ALL), we summarize insights into molecular diagnostics, immunotherapy, targeted therapy and new techniques of drug sensitivity profiling that may support further therapeutic progress in T-ALL subsets.

RECENT FINDINGS

With current induction/consolidation chemotherapy and/or risk-oriented allogeneic stem cell transplantation programs up to 95% adult T-ALL patients achieve a remission and >50% (up to 80% in adolescents and young adults) are cured. The group of patients who fail upfront therapy, between 25% and 40%, is enriched in high-risk characteristics (unfavorable genetics, persistent minimal residual disease) and represents the ideal setting for the study of molecular mechanisms of disease resistance, and consequently explore novel ways of restoration of drug sensitivity and assess patient/subset-specific patterns of drug vulnerability to targeting agents, immunotherapy and cell therapy.

SUMMARY

The emerging evidence supports the contention that precision medicine may soon allow valuable therapeutic chances to adult patients with high-risk T-ALL. The ongoing challenge is to identify the best way to integrate all these new data into the therapeutic path of newly diagnosed patients, with a view to optimize the individual treatment plan and increase the cure rate.

摘要

目的综述

为了综述成人 T 细胞急性淋巴细胞白血病(T-ALL)治疗的最新进展,我们总结了分子诊断、免疫疗法、靶向治疗以及药物敏感性分析新技术的最新见解,这些技术可能有助于 T-ALL 亚群的进一步治疗进展。

最新发现

目前采用诱导/巩固化疗和/或风险导向的异基因造血干细胞移植方案,高达 95%的成人 T-ALL 患者可获得缓解,超过 50%(青少年和年轻成人中高达 80%)可治愈。约 25%至 40%的初始治疗失败患者中存在高风险特征(不良遗传学、持续的微小残留病灶),这些患者是研究疾病耐药分子机制的理想对象,进而探索恢复药物敏感性的新方法,并评估靶向药物、免疫疗法和细胞疗法对患者/亚群的药物敏感性模式。

总结

新出现的证据支持这样一种观点,即精准医学可能很快为高危 T-ALL 成人患者提供有价值的治疗机会。当前的挑战是要找到将所有这些新数据纳入新诊断患者治疗路径的最佳方法,以优化个体化治疗方案并提高治愈率。

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