Continued decitabine/all-trans retinoic acid treatment: extended complete remission in an elderly AML patient with multi-hit TP53 lesions and complex-monosomal karyotype

IF 4.8 2区医学 Q1 GENETICS & HEREDITY Clinical Epigenetics Pub Date : 2024-09-11 DOI:10.1186/s13148-024-01737-4

Johanna Thomas, Usama-Ur Rehman, Helena Bresser, Olga Grishina, Dietmar Pfeifer, Etienne Sollier, Konstanze Döhner, Christoph Plass, Heiko Becker, Claudia Schmoor, Maike de Wit, Michael Lübbert

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Abstract

DNA-hypomethylating agents (HMAs) induce notable remission rates in AML/MDS patients with TP53 mutations; however, secondary resistance often develops rapidly. In the DECIDER trial (NCT00867672), elderly AML patients (also those with adverse genetics) randomized to all-trans retinoic acid (ATRA) added to decitabine (DEC) attained significantly delayed time-to-resistance. An 82-year-old patient with a non-disruptive, in-frame TP53 mutation (p.Cys238_Asn239delinsTyr, VAF 90%) and complex-monosomal karyotype attained a complete hematologic and cytogenetic remission with DEC + ATRA, with 3.7 years survival after 30 treatment cycles that were well-tolerated. Further HMA + ATRA studies appear warranted in AML/MDS patients of different genetic risk groups ineligible for more intensive treatment. Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT00867672

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持续地西他滨/全反式维甲酸治疗：延长一名患有多基因TP53病变和复杂单体核型的老年急性髓细胞性白血病患者的完全缓解期

DNA-甲基化药物（HMAs）可显著提高TP53突变的急性髓细胞性白血病/骨髓增生异常综合症患者的缓解率；然而，继发性耐药性往往发展迅速。在 DECIDER 试验（NCT00867672）中，老年急性髓细胞性白血病患者（也包括具有不良遗传学的患者）随机接受全反式维甲酸（ATRA）联合地西他滨（DEC）治疗后，产生耐药性的时间明显推迟。一位 82 岁的患者患有非破坏性、框架内 TP53 突变（p.Cys238_Asn239delinsTyr，VAF 90%）和复杂单体核型，在接受 DEC + ATRA 治疗后，血液学和细胞遗传学完全缓解，30 个治疗周期后存活 3.7 年，且耐受性良好。对于不符合接受更多强化治疗条件的不同遗传风险组别 AML/MDS 患者，似乎有必要进一步开展 HMA + ATRA 研究。试验注册：该试验已在 ClinicalTrials.gov 注册，标识符为NCT00867672

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来源期刊

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.