Abstract
The salvage therapy in patients with relapsed/refractory acute myeloid leukemia still poses a highly unmet clinical need. Given the established activity and toxicity profiles of hypomethylating agents such as 5-aza-2'-deoxycytidine (decitabine, DAC) in patients with untreated acute myeloid leukemia (AML), we explored the therapeutic effects of dose adjusted DAC in patients with relapsed / refractory AML, and compared treatment outcome with the conventional FLAG regimen.
27 patients with relapsed/refractory AML were included in this analysis. Twelve patients were treated with DAC 20 mg/m2 per day as 1-hour intravenous infusion for consecutive five days, with additional 1-3 doses of DAC added based on response and tolerability (Table 1). Another group of 15 patients received a course of FLAG regimen as controls.
Adjustment for dose of DAC for relapsed/refractory acute myeloid leukemia
| Characteristics | Dose added |
| Cellularity | 0 |
| normal | 1 |
| increased | 0 |
| BM Blast % | 1 |
| No | 2 |
| <5% | 0 |
| ®5% | -1 |
| General condition | -1 |
| Karnofsky performance score®80 | 0 |
| Karnofsky performance score<80 | |
| Age | |
| ®60 | |
| <60 |
| Characteristics | Dose added |
| Cellularity | 0 |
| normal | 1 |
| increased | 0 |
| BM Blast % | 1 |
| No | 2 |
| <5% | 0 |
| ®5% | -1 |
| General condition | -1 |
| Karnofsky performance score®80 | 0 |
| Karnofsky performance score<80 | |
| Age | |
| ®60 | |
| <60 |
Although the overall response rates (ORR) were similar in DAC group (5/12) and FLAG group (9/15)£¨41.7 % versus 60 %, P=0.449£©, the complete remission (CR) rate plus CRi was lower in DAC group (2/12) than in FLAG group(10/15)£¨16.7 %versus 66.7 %, P=0.047£©. Induction mortality was 0 (0% at 8 weeks) and toxicities were manageable in both groups. Toxicities were predominantly hematologic. The most common drug-related adverse events (AEs£© were grade 4 myelosuppression which were comparable for DAC and FLAG., DAC group hadfewer infections£¨DAC, 6/12£»FLAG£€n=14/15, P=0.024£©. The 2-year survival rate was similar in the two groups: 25.0% in the DAC versus 26.7% in the FLAG group£¨P=0.574£©, while median survival times of the two groups were 4 and 12 months, respectively.
Dose-adjusted DAC achieved similar overall response rate with lower infection risk compared to FLAG regimen in patients with relapsed / refractory AML.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
