Braulke Friederike, Schulz Xenia, Germing Ulrich, Schuler Esther, Platzbecker Uwe, Nolte Florian, Hofmann Wolf-Karsten, Giagounidis Aristoteles, Götze Katharina, Lübbert Michael, Schlenk Richard F, Schanz Julie, Bacher Ulrike, Ganser Arnold, Büsche Guntram, Letsch Anne, Schafhausen Philippe, Bug Gesine, Brümmendorf Tim H, Haas Rainer, Trümper Lorenz, Shirneshan Katayoon, Haase Detlef
Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany.
Department of Medical Statistics, University Medicine of Goettingen, Goettingen, Germany.
Ann Hematol. 2017 Jun;96(6):887-894. doi: 10.1007/s00277-017-2983-0. Epub 2017 Apr 3.
Transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndrome, <5% bone marrow (BM) blasts and isolated 5q-deletion received lenalidomide within the German MDS study group phase-II clinical trial LE-MON-5 (EudraCT:2008-001866-10) of the University of Duesseldorf, Germany. Cytogenetic monitoring was performed by chromosome banding analyses (CBA) of BM cells and fluorescence in situ hybridization (FISH) analyses of peripheral blood (PB) mononuclear CD34+ cells using extended probe panels. Out of 144 patients screened for study enrollment, 24% failed to meet inclusion criteria due to cytogenetic findings. Eighty-seven patients were followed with a median observation time of 30 months. Cytogenetic response detected by FISH and CBA in 74 and 66% of patients, respectively, was predictive for hematologic response as well as of high prognostic relevance. After 2 years, AML rate was 8% for all patients. Karyotype evolution was detected in 21 (FISH)-34% (CBA) of patients associated with significantly shorter AML-free survival. Disease progression was first detectable on the cytogenetic level on average 5-6 months before recurrence of transfusion dependence. Our data show for the first time in a prospective setting that a cytogenetic monitoring from the PB helps to early identify treatment failure and progressive disease in lenalidomide-treated patients to improve clinical management.
EudraCT:2008-001866-10.
在德国杜塞尔多夫大学进行的德国骨髓增生异常综合征研究组II期临床试验LE-MON-5（欧洲临床试验注册号：2008-001866-10）中，患有低危或中危1型骨髓增生异常综合征、骨髓（BM）原始细胞<5%且孤立性5q缺失的输血依赖患者接受了来那度胺治疗。通过对BM细胞进行染色体显带分析（CBA）以及使用扩展探针组对外周血（PB）单核CD34+细胞进行荧光原位杂交（FISH）分析来进行细胞遗传学监测。在144名筛选纳入研究的患者中，24%因细胞遗传学检查结果未达到纳入标准。87名患者接受随访，中位观察时间为30个月。分别在74%和66%的患者中通过FISH和CBA检测到的细胞遗传学反应可预测血液学反应，且具有高度预后相关性。2年后，所有患者的急性髓系白血病（AML）发生率为8%。在21%（FISH）-34%（CBA）的患者中检测到核型演变，这与显著缩短的无AML生存期相关。疾病进展平均在输血依赖复发前5-至6个月首次在细胞遗传学水平上被检测到。我们的数据首次在前瞻性研究中表明，对外周血进行细胞遗传学监测有助于早期识别来那度胺治疗患者的治疗失败和疾病进展，从而改善临床管理。
欧洲临床试验注册号：2008-001866-10。
