Comprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real-world cohort of patients with lower-risk MDS

IF 7.6 2区 医学 Q1 HEMATOLOGY HemaSphere Pub Date : 2024-09-23 DOI:10.1002/hem3.70014
Paolo Mazzeo, Christina Ganster, John Wiedenhöft, Katayoon Shirneshan, Katharina Rittscher, Elzbieta B. Brzuszkiewicz, Doris Steinemann, Maximilian Schieck, Catharina Müller-Thomas, Hannes Treiber, Friederike Braulke, Ulrich Germing, Katja Sockel, Ekaterina Balaian, Julie Schanz, Uwe Platzbecker, Katharina S. Götze, Detlef Haase
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Abstract

The acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high-risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower-risk MDS (LR-MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real-world cohort of LR-MDS patients. We screened 68 patients with a median follow-up of 40.5 months and a median of 7.5 (range: 2–22) timepoints for CE and CEXP detected by chromosomal banding analysis, fluorescence in situ hybridization, sequencing, and molecular karyotyping. In 30/68 patients, 47 CE events and a CD rate of 1 event per 4 years were documented. Of note, patients with at least 1 CE event had an increased probability for subsequent treatment. Unexpectedly, CE did not correlate with inferior outcomes, which could be reasonably explained by CD detection triggering the subsequent start of a disease-modifying therapy.

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在低风险 MDS 患者的真实世界队列中进行全面的序列遗传分析,确定基因组动态的频率、模式和对预后的影响。
骨髓增生异常综合征(MDS)的后续遗传病变(克隆进化,CE)和/或现有克隆的扩增(CEXP)促成了克隆动态(CD)。虽然克隆动态变化在高危患者的疾病进展和转化为急性髓性白血病(AML)过程中起着重要作用,但由于缺乏可靠的纵向数据,对低危 MDS(LR-MDS)患者克隆动态变化的了解十分有限,因为这种疾病的临床病程较长,病情稳定。在这项回顾性分析中,我们描述了未经筛选的 LR-MDS 患者真实世界队列中 CD 的发生频率及其对预后的影响。我们对 68 例患者进行了筛查,中位随访时间为 40.5 个月,中位时间点为 7.5 个(范围:2-22),通过染色体条带分析、荧光原位杂交、测序和分子核型分析检测出 CE 和 CEXP。在 30/68 例患者中,有 47 例 CE 事件记录在案,CD 发生率为每 4 年 1 例。值得注意的是,至少发生过一次 CE 事件的患者接受后续治疗的概率增加。出乎意料的是,CE 并不与较差的预后相关,这可以合理地解释为 CD 检测触发了随后开始的疾病改变疗法。
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来源期刊
HemaSphere
HemaSphere Medicine-Hematology
CiteScore
6.10
自引率
4.50%
发文量
2776
审稿时长
7 weeks
期刊介绍: HemaSphere, as a publication, is dedicated to disseminating the outcomes of profoundly pertinent basic, translational, and clinical research endeavors within the field of hematology. The journal actively seeks robust studies that unveil novel discoveries with significant ramifications for hematology. In addition to original research, HemaSphere features review articles and guideline articles that furnish lucid synopses and discussions of emerging developments, along with recommendations for patient care. Positioned as the foremost resource in hematology, HemaSphere augments its offerings with specialized sections like HemaTopics and HemaPolicy. These segments engender insightful dialogues covering a spectrum of hematology-related topics, including digestible summaries of pivotal articles, updates on new therapies, deliberations on European policy matters, and other noteworthy news items within the field. Steering the course of HemaSphere are Editor in Chief Jan Cools and Deputy Editor in Chief Claire Harrison, alongside the guidance of an esteemed Editorial Board comprising international luminaries in both research and clinical realms, each representing diverse areas of hematologic expertise.
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