Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care.
Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care.
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DOI：
10.1038/s41375-018-0257-z
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发表时间：
2018-12
期刊：
影响因子：
11.4
通讯作者：
Dombret H
中科院分区：
文献类型：
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作者：
Döhner H;Dolnik A;Tang L;Seymour JF;Minden MD;Stone RM;Del Castillo TB;Al-Ali HK;Santini V;Vyas P;Beach CL;MacBeth KJ;Skikne BS;Songer S;Tu N;Bullinger L;Dombret H
在 3 期 AZA-AML-001 研究中，对新诊断的急性髓系白血病 (AML) 的老年患者在入组时进行了细胞遗传学异常评估，并对一部分患者进行了基因突变评估。患者接受阿扎胞苷 75mg/m2/天 x7 天 (n = 240) 或常规护理方案 (CCR; n = 245)：强化化疗、低剂量阿糖胞苷或仅最佳支持治疗。对具有常见（≥10%）细胞遗传学异常和核型的患者以及具有复发性基因突变的患者评估了总生存期 (OS)。对于欧洲白血病网定义的不良核型患者，阿扎胞苷与 CCR 相比，OS 显着改善（HR 0.71 [95%CI 0.51–0.99]；P = 0.046）。与 CCR 相比，接受阿扎胞苷治疗的具有 -5/5q-、-7/7q- 或 17p 异常或单体或复杂核型的患者的死亡风险降低了 31-46%。最常见的基因突变是 DNMT3A (27%)、TET2 (25%)、IDH2 (23% [R140, 15%; R172, 8%]) 和 TP53 (21%)。与野生型相比，接受 CCR 治疗的 TP53 或 NRAS 突变患者以及接受阿扎胞苷治疗的 FLT3 或 TET2 突变患者的 OS 显着降低。阿扎胞苷可能是具有不良细胞遗传学风险的老年 AML 患者的首选治疗方法，特别是具有 5、7 和/或 17 号染色体异常以及复杂或单体核型的患者。基因突变对阿扎胞苷治疗患者的影响值得进一步研究。
Older patients with newly diagnosed acute myeloid leukemia (AML) in the phase 3 AZA-AML-001 study were evaluated at entry for cytogenetic abnormalities, and a subgroup of patients was assessed for gene mutations. Patients received azacitidine 75 mg/m2/day x7 days (n = 240) or conventional care regimens (CCR; n = 245): intensive chemotherapy, low-dose cytarabine, or best supportive care only. Overall survival (OS) was assessed for patients with common (occurring in ≥10% of patients) cytogenetic abnormalities and karyotypes, and for patients with recurring gene mutations. There was a significant OS improvement with azacitidine vs CCR for patients with European LeukemiaNet-defined Adverse karyotype (HR 0.71 [95%CI 0.51–0.99]; P = 0.046). Azacitidine-treated patients with -5/5q-, -7/7q-, or 17p abnormalities, or with monosomal or complex karyotypes, had a 31–46% reduced risk of death vs CCR. The most frequent gene mutations were DNMT3A (27%), TET2 (25%), IDH2 (23% [R140, 15%; R172, 8%]), and TP53 (21%). Compared with wild-type, OS was significantly reduced among CCR-treated patients with TP53 or NRAS mutations and azacitidine-treated patients with FLT3 or TET2 mutations. Azacitidine may be a preferred treatment for older patients with AML with Adverse-risk cytogenetics, particularly those with chromosome 5, 7, and/or 17 abnormalities and complex or monosomal karyotypes. The influence of gene mutations in azacitidine-treated patients warrants further study.
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影响因子：
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作者：
Devillier R;Mansat-De Mas V;Gelsi-Boyer V;Demur C;Murati A;Corre J;Prebet T;Bertoli S;Brecqueville M;Arnoulet C;Recher C;Vey N;Mozziconacci MJ;Delabesse E;Birnbaum D
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影响因子：
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50.3
作者：
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通讯作者：
Shih AH
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
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Melnick A
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作者：
Jung SH;Kim YJ;Yim SH;Kim HJ;Kwon YR;Hur EH;Goo BK;Choi YS;Lee SH;Chung YJ;Lee JH
通讯作者：
Lee JH