Alfonso Ana, Montalban-Bravo Guillermo, Takahashi Koichi, Jabbour Elias J, Kadia Tapan, Ravandi Farhad, Cortes Jorge, Estrov Zeev, Borthakur Gautam, Pemmaraju Naveen, Konopleva Marina, Bueso-Ramos Carlos, Pierce Sherry, Kantarjian Hagop, Garcia-Manero Guillermo
Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
Departments of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
Am J Hematol. 2017 Jul;92(7):599-606. doi: 10.1002/ajh.24735. Epub 2017 May 26.
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 < .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.
去甲基化药物（HMA）是慢性粒单核细胞白血病（CMML）中最常用的治疗干预手段。由于缺乏针对CMML的临床试验，这些药物对CMML自然病程的影响尚未完全明确。我们呈现了接受HMA治疗的最大规模CMML回顾性系列研究（n = 151）。诊断时的平均年龄为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-1危，42例（36%）为中-2危，12例（10%）为高危。35例（23%）患者接受单药阿扎胞苷治疗，73例（48%）接受单药地西他滨治疗，43例（29%）接受联合治疗。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）。多因素分析显示，年龄＜70岁、血红蛋白水平较高、外周血无原始细胞以及CPSS细胞遗传学风险较低预示着更好的总生存期。接受地西他滨治疗的患者完全缓解率（58.3%）显著高于接受阿扎胞苷治疗的患者（20.6%）（P＜0.001）。13例患者（9%）在接受中位4个周期的HMA治疗后接受了异基因造血干细胞移植（allo - SCT）。66例患者（50%）出现HMA治疗失败：26例为原发性失败（34%），50例为继发性失败（66%），其中35例（46%）转化为急性髓系白血病（AML）。HMA治疗失败后的预后较差，总生存期为7个月（95%CI：3 - 12）。总之，HMA对CMML有效，但需要新的药物和联合方案。这些数据可为CMML的进一步药物研发提供基准。
