Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents.
Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents.
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DOI：
10.1002/ajh.24735
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发表时间：
2017-07
影响因子：
12.8
通讯作者：
Garcia-Manero G
中科院分区：
文献类型：
--
作者：
Alfonso A;Montalban-Bravo G;Takahashi K;Jabbour EJ;Kadia T;Ravandi F;Cortes J;Estrov Z;Borthakur G;Pemmaraju N;Konopleva M;Bueso-Ramos C;Pierce S;Kantarjian H;Garcia-Manero G
低甲基化药物（HMA）是慢性髓细胞白血病（CMML）最常用的治疗干预措施。由于缺乏CMML特异性临床试验，这些药物在CMML自然史中的影响尚不完全清楚。我们提出了最大的回顾性系列CMML （n=151）治疗HMA。诊断时平均年龄为69岁（范围50-88岁）。根据cmml特异性预后评分系统（CPSS）： 17例（15%）为低危，45例（39%）为中危，42例（36%）为中危，12例（10%）为高危。35例（23%）患者使用单药阿扎胞苷，73例（48%）使用单药地西他滨，43例（29%）使用联合用药。中位随访17个月，总缓解率（ORR）为75%，41%达到完全缓解（CR）。中位总生存期（OS）为24个月（95%CI: 20-28），无事件生存期为14个月（95%CI: 11-17）。通过多因素分析，年龄< 70岁、血红蛋白水平较高、外周血中没有母细胞和较低的CPSS细胞遗传学风险预示着较好的OS。地西他滨组患者的CR（58.3%）明显高于阿扎胞苷组（20.6%）（p<0.001）。13例患者（9%）在平均4个HMA周期后接受了同种异体细胞移植。66例患者（50%）HMA失败：26例原发性（34%）和50例继发性（66%），其中35例（46%）转化为AML。HMA失败后的结果较差，OS为7个月（95%CI: 3-12）。总之，HMA治疗CMML是有效的，但需要新的药物和组合。这些数据可以作为进一步开发CMML药物的基准。
Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n=151) treated with HMA. Mean age at diagnosis was 69 years (range 50–88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk. 35 (23%) patients received single agent azacitidine, 73 (48%) single agent decitabine, and 43 (29%) combinations. With a median follow-up of 17 months, overall response rate (ORR) was 75%, with 41% achieving complete response (CR). Median overall survival (OS) was 24 months (95%CI: 20–28) and event-free survival 14 months (95%CI: 11–17). By multivariate analysis, age < 70 years, higher levels of hemoglobin, absence of blast in peripheral blood and lower CPSS cytogenetic risk predicted for better OS. CR was significantly higher in those patients treated with decitabine (58.3%) when compared with azacitidine (20.6%) (p<0.001). 13 patients (9%) received allo-SCT after a median of 4 cycles of HMA. 66 patients (50%) had HMA failure: 26 primary (34%) and 50 secondary (66%), including 35 (46%) that transformed to AML. Outcomes after HMA failure were poor with OS of 7 months (95%CI: 3–12). In conclusion, HMA are effective in CMML but new agents and combinations are needed. This data could be a benchmark for further drug development in CMML.
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影响因子：
6.2
作者：
Jabbour, Elias;Garcia-Manero, Guillermo;Batty, Nicolas;Shan, Jenny;O'Brien, Susan;Cortes, Jorge;Ravandi, Farhad;Issa, Jean-Pierre;Kantarjian, Hagop
通讯作者：
Kantarjian, Hagop
影响因子：
2.7
作者：
Duong, Vu H.;Lin, Karen;Komrokji, Rami S.
通讯作者：
Komrokji, Rami S.
影响因子：
3.1
作者：
Park, Sophie;Labopin, Myriam;Mohty, Mohamad
通讯作者：
Mohty, Mohamad
影响因子：
2.7
作者：
Itonaga, Hidehiro;Iwanaga, Masako;Miyazaki, Yasushi
通讯作者：
Miyazaki, Yasushi
影响因子：
20.3
作者：
Greenberg, P;Cox, C;Bennett, J
通讯作者：
Bennett, J