A limited number of 5-azacitidine cycles can be effective treatment in MDS

Hypomethylating agents, such as 5-azacitidine (5-AZA) and 5-aza-2’-deoxycytidine (decitabine), have recently been approved for the treatment of myelodysplastic syndromes (MDS). Several randomized trials have shown favorable results concerning response rate, survival, transformation to acute leukemia, and quality of life. In these trials, treatment was administered continuously until progression. In the retrospective study presented here, we evaluated the outcome of patients with higher risk MDS or secondary acute myeloid leukemia (sAML) treated with a limited number of 5-AZA cycles. A total of 32 patients received 5-AZA alone (n = 30) or in combination with valproic acid and all-trans retinoic acid (n = 2). 5-AZA was administered subcutaneously at a fixed dose of 75 mg/m² daily for 7 days and repeated every 28 days. 5-AZA was given for a median of four courses. Treatment was continued for two more cycles as consolidation in patients who had achieved complete remission (CR), marrow CR, or stable disease with hematologic improvement. The overall response rate was 50% according to the modified International Working Group criteria. Complete remissions were achieved in 15.6% and stable disease in 34.4% of patients. Peripheral blood counts normalized in 6.3% of patients while hematologic improvement was achieved in 25%. The median time to AML in responding patients was 45 weeks, while AML occurred after a median of 14 weeks in non-responding patients (P = .038). The median survival of all patients was 60 weeks; the median survival of responders was 74 weeks compared with 26 weeks in non-responders (P = .047). In this retrospective analysis, 5-AZA was associated with a survival advantage in responding patients with higher risk MDS or sAML. These favorable results suggest that patients may benefit even from a limited number of courses of 5-AZA. A randomized controlled clinical trial is required to prospectively validate these findings.