Prognostic significance of serial molecular annotation in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML).
Prognostic significance of serial molecular annotation in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML).
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DOI：
10.1038/s41375-020-0997-4
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发表时间：
2021-04
期刊：
影响因子：
11.4
通讯作者：
Sallman DA
中科院分区：
文献类型：
--
作者：
Yun S;Geyer SM;Komrokji RS;Al Ali NH;Song J;Hussaini M;Sweet KL;Lancet JE;List AF;Padron E;Sallman DA
下一代测序（NGS）的实施已经影响了髓系恶性肿瘤的诊断、预后和治疗决策。然而，在接受积极治疗的骨髓增生异常综合征（MDS）患者中，序列分子注释的临床意义尚不清楚。MDS或继发性急性髓性白血病（sAML）患者至少进行了两次NGS评估。根据突变清除率（NGS-）进行系列评估。采用单因素和多因素Cox回归模型评估NGS轨迹对总生存期（OS）的预后影响。共发现157例患者（MDS [n=95]; sAML [n=52]; CMML [n=10]）， 93%的患者在NGS评估期间接受治疗。从基线开始的VAF δ的大小与对治疗的反应质量显著相关。与突变持续性患者相比，获得NGS-的患者的生存期显著改善（未达到中位生存期vs 18.5个月；P=0.002），多因素分析证实了这一点（HR,0.14; 95%CI= 0.03-0.56； P=0.0064）。连续TP53 VAF评估预测结果，TP53清除率代表高OS的独立协变量（HR,0.22; 95%CI= 0.05-0.99； P=0.048）。总的来说，我们的研究强调了在治疗过程中一系列NGS的临床价值，并保证了NGS阴性作为治疗结果生物标志物的前瞻性验证。
The implementation of next generation sequencing (NGS) has influenced diagnostic, prognostic, and therapeutic decisions in myeloid malignancies. However, the clinical relevance of serial molecular annotation in patients with myelodysplastic syndrome (MDS) undergoing active treatment is unknown. MDS or secondary acute myeloid leukemia (sAML) patients who had at least two NGS assessments were identified. Outcomes according to mutation clearance (NGS-) on serial assessment were investigated. Univariate and multivariate Cox regression models were used to evaluate the prognostic impact of NGS trajectory on overall survival (OS). A total of 157 patients (MDS [n=95]; sAML [n=52]; CMML [n=10]) were identified, with 93% of patients receiving treatment between NGS assessments. Magnitude of VAF delta from baseline was significantly associated with quality of response to treatment. Patients achieving NGS- had significantly improved OS compared to patients with mutation persistence (median OS not reached versus 18.5 months; P=0.002), which was confirmed in multivariate analysis (HR,0.14; 95%CI=0.03–0.56; P=0.0064). Serial TP53 VAF evaluation predicts outcomes with TP53 clearance representing an independent covariate for superior OS (HR,0.22; 95%CI=0.05–0.99; P=0.048). Collectively, our study highlights the clinical value of serial NGS during treatment and warrants prospective validation of NGS negativity as a biomarker for treatment outcome.
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影响因子：
30.8
作者：
Makishima H;Yoshizato T;Yoshida K;Sekeres MA;Radivoyevitch T;Suzuki H;Przychodzen B;Nagata Y;Meggendorfer M;Sanada M;Okuno Y;Hirsch C;Kuzmanovic T;Sato Y;Sato-Otsubo A;LaFramboise T;Hosono N;Shiraishi Y;Chiba K;Haferlach C;Kern W;Tanaka H;Shiozawa Y;Gómez-Seguí I;Husseinzadeh HD;Thota S;Guinta KM;Dienes B;Nakamaki T;Miyawaki S;Saunthararajah Y;Chiba S;Miyano S;Shih LY;Haferlach T;Ogawa S;Maciejewski JP
通讯作者：
Maciejewski JP
DOI：
10.1056/nejmoa1013343
发表时间：
2011-06-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bejar R;Stevenson K;Abdel-Wahab O;Galili N;Nilsson B;Garcia-Manero G;Kantarjian H;Raza A;Levine RL;Neuberg D;Ebert BL
通讯作者：
Ebert BL
影响因子：
20.3
作者：
Papaemmanuil, Elli;Gerstung, Moritz;Campbell, Peter J.
通讯作者：
Campbell, Peter J.
影响因子：
20.3
作者：
Greenberg, Peter L.;Tuechler, Heinz;Haase, Detlef
通讯作者：
Haase, Detlef
影响因子：
45.3
作者：
Bejar, Rafael;Stevenson, Kristen E.;Ebert, Benjamin L.
通讯作者：
Ebert, Benjamin L.