【摘要】 目的 探讨异基因造血干细胞移植（allo-HSCT）治疗ASXL1基因突变（ASXL1~+）的骨髓增生异常综合征（MDS）患者的疗效及影响因素。方法 对247例初诊为MDS患者进行二代测序技术检测22种基因突变情况。根据治疗方式分为化疗组和移植组，比较两组总生存期（OS）、无进展生存期（PFS）的差异，并对移植患者预后的影响因素进行分析。结果 75例（30.36%）患者检测到ASXL1~+，中位突变比例为42.93(18.10,58.39)%。其中10例接受支持治疗，43例接受化疗，22例接受allo-HSCT，移植组2年OS及PFS率较化疗组显著增加（P <0.05）；移植组ASXL1低突变负荷组（VAF≤42.93%）2年OS率较ASXL1高突变负荷（VAF> 42.93%）组显著增加（P <0.05）。在ASXL1~+患者接受allo-HSCT的背景下，RUNX1基因突变（RUNX1~+）或U2AF1基因突变（U2AF1~+）患者的2年OS率及PFS率显著减低（P <0.05）。进行多因素分析结果显示，ASXL1高突变负荷、U2AF1~+是影响移植患者OS的独立危险因素（P <0.05）。U2AF1~+是移植患者PFS的独立危险因素（P <0.05）。结论 allo-HSCT显著改善了ASXL1~+MDS患者的预后，ASXL1高突变负荷、U2AF1~+是影响移植疗效的独立危险因素。更多还原

【Abstract】 Objective To investigate the efficacy and influencing factors of allo-HSCT in the treatment of MDS patients with ASXL1~+. Methods The second-generation sequencing technique was used to detect 22 gene mutations in 247 newly diagnosed MDS patients in our hospital. The patients were divided into chemotherapy group and transplant group according to treatment style. The differences of OS and PFS between the two groups were compared, and the influencing factors of prognosis of transplant patients were analyzed. Results ASXL1~+ was detected in 75 patients(30.36%), with a median mutation ratio of 42.93(18.10,58.39)%, 10 received supportive treatment, 43 received demethylation therapy or demethylation combined with pre-excitation therapy, and 22 received allo-HSCT. 2-year PFS rate and OS rate of transplantation group were significantly higher than that of chemotherapy group(P < 0.05). The 2-year OS rate in the low ASXL1 mutation load group(VAF ≤ 42.93%) was significantly higher than that in the high ASXL1 mutation load group(VAF > 42.93%)(P < 0.05). In the context of allo-HSCT in patients with ASXL1~+, 2-year OS and PFS rates were significantly reduced in patients with RUNX1~+ or ASXL1~+(P <0.05); Multivariate analysis showed that high mutation load of ASXL1 or U2AF1~+ were independent risk factors for OS in transplant patient(P < 0.05). U2AF1~+ were the risk factors for PFS(P < 0.05). Conclusion allo-HSCT significantly improved the prognosis of patients with ASXL1~+ MDS. High ASXL1 mutation load or U2AF1~+ were independent risk factors affecting the outcome of allo-HSCT.更多还原