The Application of Decitabine in Combination with G-CSF, Low-Dose Cytarabine and Aclarubicin in AML-MRC: A Single Center Case Control Study

Background: It is difficult for AML-MRC patients to achieve complete remission (CR) and these patients develop recurrence and die of either disease progression or associated complications. The CAG regimen (cytarabine, aclarubicin and G-CSF) has been widely used in treating patients with AML-MRC in Asia. Decitabine (DAC) was approved to the treatment of MDS and reported to achieve higher response rate (67%) in AML with unfavorable-risk cytogenetics. Several studies reported low dose DAC in combination with chemotherapy to treat AML.

Purpose:To evaluate the clinical efficacy and safety of low-dose decitabine in combination with small-dose CAG regimen (D-CAG regimen) in the treatment of AML-MRC, compared to CAG regimen.

Methods:A total of 80 patients with newly diagnosed AML-MRC from September 2015 to January 2020 in our center were included in the study. 43 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10-mg/ m ²q12h for 14 days and aclarubicin of 20 mg/day for 4 days (CAG regimen) and other 37 cases were initially treated with decitabine of 20 mg/m ² for 5 days and small-dose CAG regimen (cytarabine of 10-mg/ m ²q12h for 7 days, aclarubicin of 10 mg/day for 4 days, and G-CSF for priming (D-CAG regimen). After induction chemotherapy, the patients who achieved CR received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT).

Results:Among a total of 80 patients, the median age was 55 years (18-69 years) and 32 of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences (table 1). For the overall AML-MRC patients, the MLFS rate of D-CAG group was higher than the MLFS rate of CAG group after two courses of D-CAG regimen (62.2% v. s. 48.8%, χ2 =8.727, P=0.013, bilateral). Seven patients in CAG group did not response and then received D-CAG regimen as induction therapy, and five of them achieved MLFS (5/7) and one achieved PR (1/7). Among the population with less than 9 months of AML-MRC and/or MDS history, the MLFS rate (74.1%, 20/27) of D-CAG group was statistically higher than the MLFS rate (42.9% 15/35) of CAG group (74.1% v. s. 42.9%, χ ² =1.909, p=0.008). Compared to the CAG group, the high-risk patients classified according to SWOG criteria in D-CAG group achieved a better MLFS rate (80.0% v. s. 26.1%, χ ² =11.392, P=0.003, bilateral). Except patients receiving HSCT, the probability of OS and LFS for patients between D-CAG group and CAG group did not show any significant difference, but among the population with less than 9 months of AML-MRC and/or MDS history, the DCAG group showed a better probability of OS than the CAG group (58.3%±18.6% v. s. 11.3%±10.3%, p=0.006).

Conclusion: In conclusion, patients with AML-MRC have a poor prognosis, and might benefit from D-CAG regimen as the induction therapy. For patients with less than 9 months of AML-MRC/MDS history or with poor karyotypes, the MLFS rate for patients in D-CAG group was higher than patients in CAG group.