Objective: To assess the efficiency and safety of low-dose decitabine in patients with lower-risk myelodysplastic syndrome (MDS) to couple with the clinical significance of MDS-related gene mutations. Methods: This study was done in 4 institutions in Zhejiang Province. A total of 62 newly diagnosed patients with lower-risk MDS were assigned to two groups of decitabine (12 mg·m(-2)·d(-1) for 5 consecutive days) and best supportive care (BSC) . Their bone marrow samples were subject to examinations of MDS-related 15 gene mutations. The primary endpoints were the proportion of patients who achieved overall response (ORR) after at least two cycles and progression-free survival (PFS) , and their relevances to the gene mutations. Results: Of 62 enrolled patients, and 51 cases were included in the final analysis. 16 of 24 patients (66.7%) in decitabine group achieved ORR versus 8 of 27 (29.6%) in BSC group (χ(2)=6.996, P=0.008) ; PFS prolongation of decitabine versus BSC was statistically significant (not reached vs 13.7 months, P=0.037) . Among 51 patients, at least one gene mutation was identified in 20 patients (39.2%) , including 4 single SF3B1 mutation. PFS in cases with gene mutations (not including single SF3B1 mutation) was significantly shorter than of no gene mutation (9.2 months vs 18.5 months, P=0.008) , but not for ORR (37.5% vs 58.1%, P=0.181) . Among 16 patients with mutated genes, ORR in decitabine and BSC groups were 75% (6/8) and 0 (0/8) , respectively. The most adverse events in decitabine group were grade 3 to 4 neutropenia (45.8%) and grade 3 to 4 infections (33.3%) . Conclusion: This preliminary study showed that low-dose decitabine produced promising results with an acceptable safety in lower-risk MDS patients, especially for those with mutated genes. Further study targeting poor prognostic lower-risk MDS patients should be warranted.
目的： 评价小剂量地西他滨治疗较低危骨髓增生异常综合征（MDS）患者的初步疗效及安全性，探讨MDS相关基因突变的临床意义。 方法： 纳入浙江省4所医院收治的62例较低危MDS患者，治疗分2组，地西他滨组（地西他滨12 mg·m(-2)·d(-1)，连续5 d）和支持治疗组，检测与MDS预后相关的15项基因突变情况。比较两组患者的总体有效率（ORR）和无进展生存（PFS）时间，分析其与基因突变的相关性。 结果： 62例患者中，可评估患者51例，其中地西他滨组24例，支持治疗组27例。与支持治疗组相比，地西他滨组的ORR（66.7%对29.6%，χ(2)=6.996，P=0.008）和中位PFS时间显著改善（未达到对13.7个月，P=0.037）。51例患者中20例（39.2%）检测到基因突变阳性，其中4例患者单纯SF3B1阳性，均在支持治疗组。与基因突变阴性患者相比，16例基因突变阳性（除单纯SF3B1阳性）患者中位PFS时间显著缩短（9.2个月对18.5个月，P=0.008），其中地西他滨组8例患者中6例有效，支持治疗组无一例（0/8）有效。地西他滨治疗期间主要不良反应为3~4级粒细胞减少（45.8%），3~4级感染发生率为33.3%（8/24）。 结论： 该研究小系列患者的初步结果表明应用小剂量地西他滨治疗较低危MDS患者可能有效，对于基因突变患者也可获益，且患者耐受，值得临床试验进一步明确其临床意义。.
Keywords: Decitabine; Hypomethylating; Lower-risk; Myelodysplastic syndromes.