Objective: To evaluate the clinical efficacy and safety of decitabine in combination with lower-dose CAG regimen (G-CSF, cytarabine and aclarubicin; D-CAG regimen) in the treatment of myelodysplastic syndromes with excess blasts (MDS-EB) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), compared to standard CAG regimen. Methods: A total of 42 patients with newly diagnosed MDS-EB and AML-MRC from May 2011 to March 2017 were included in the retrospective study. 21 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10 mg/m(2) q12h for 14 days and aclarubicin of 20 mg/d for 4 days (CAG regimen) and the other 21 cases were initially treated with decitabine of 20 mg/m(2) for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m(2) q12h for 7 days, aclarubicin of 10 mg/d for 4 days, and G-CSF for priming (D-CAG regimen). After two cycles of induction chemotherapy, the patients who obtained complete remission(CR) received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results: Among a total of 42 patients, the median age was 52.5 years (18-65 years) and 64.3% of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences. The CR for patients in D-CAG group was 81.0% (17/21), compared to 52.4% (11/21) in CAG group after 2 cycles of therapy (χ(2)=3.857, P=0.050). The overall response rate (ORR) for patients in D-CAG group and CAG group was 85.7% (18/21) and 76.2% (15/21) respectively, without significant difference (χ(2)=1.273, P=0.259). By December 2017, the median follow-up of D-CAG group and CAG group was 13(6-32) months and 15(2-36) months respectively. Finally, 10 patients in D-CAG group and 7 patients in CAG group received HSCT respectively. Except patients receiving HSCT, the median leukemia-free survival (LFS) time for patients in D-CAG group and CAG group was 18.0 (95%CI 6.6-29.4) months and 11.0 (95%CI 0-23.9) months respectively. Probabilities of 12 months LFS for D-CAG group and CAG group were (63.6±14.5)% and (50.0±13.4)% respectively, without difference (χ(2)=0.049, P=0.824). Except patients receiving HSCT, there were 2 deaths in D-CAG group and 7 deaths in CAG group respectively. The cumulative probabilities of 12 months OS for non-HSCT patients in D-CAG group and CAG group were (90.9±8.7)% and (61.5±13.5)% respectively, without significant difference (χ(2)=1.840, P=0.175). The incidences of side effects between D-CAG group and CAG group did not show significant differences (P=0.479), and the main side effects included cytopenias, pneumonia, infections of skin and soft tissues, neutropenic patients with fever, liver dysfunction. Conclusion: The decitabine in combination with lower-dose CAG regimen improved CR for patients with MDS-EB and AML-MRC, and was a promising choice.
目的： 比较地西他滨（DAC）联合半量CAG方案（D-CAG）与CAG方案治疗骨髓增生异常综合征伴原始细胞增多（MDS-EB）和急性髓系白血病伴骨髓增生异常相关改变（AML-MRC）的临床疗效及安全性。 方法： 回顾性分析2011年5月至2017年3月42例初治MDS-EB和AML-MRC患者临床资料，21例接受D-CAG治疗，21例接受CAG方案治疗，诱导缓解后患者继续巩固化疗或进行allo-HSCT。比较两组患者的CR率、总有效率（ORR）、总生存（OS）率、无病生存（DFS）率和不良反应发生率。 结果： 42例MDS-EB和AML-MRC患者中，男27例，女15例，中位年龄52.5（18~65）岁；MDS-EB 21例，AML-MRC 21例。D-CAG组和CAG组年龄、性别、疾病类型、基因突变类型和染色体核型差异均无统计学意义。D-CAG组2个疗程CR率为81.0%（17/21），高于CAG组的52.4%（11/21）（χ(2)=3.857，P=0.050）。D-CAG组与CAG组2个疗程后ORR分别为85.7%（18/21）与76.2%（15/21），差异无统计学意义（χ(2)=1.273，P=0.259）。D-CAG组和CAG组的中位随访时间分别为13（6~32）个月和15（2~36）个月，D-CAG组10例患者接受了allo-HSCT，CAG组7例患者接受了allo-HSCT。D-CAG组非移植患者的中位LFS时间为18.0（95%CI 6.6~29.4）个月，CAG组非移植患者的中位LFS时间为11.0（95%CI 0~23.9）个月，两组1年累积LFS率分别为（63.6±14.5）%和（50.0±13.4）%，差异无统计学意义（χ(2)=0.049，P=0.824）。D-CAG组11例非移植患者中2例死亡，CAG组非移植的14例患者中7例死亡，D-CAG组与CAG组非移植患者的1年累积OS率为（90.9±8.7）%对（61.5±13.5）%，D-CAG组高于CAG组，但差异无统计学意义（χ(2)=1.840，P=0.175）。D-CAG组主要的不良反应为骨髓抑制所致的感染，化疗后肺部感染发生率为42.9%，与CAG组（38.1%）差异无统计学意义（P=0.753）。 结论： DAC联合半量CAG方案治疗初治MDS-EB和AML-MRC患者的CR率高于CAG方案，且不良反应与CAG方案相当，对患者长期生存的影响有待进一步观察。.
Keywords: CAG regimen; D-CAG regimen; Myelodysplastic syndromes; Treatment outcome.