The Equal Activity of Azacytidine in 4 Risk Groups of IPSS in MDS.

Introduction: The methylated proportion of the gene, turning on the cell cycle, increases with a progression of MDS. Newly introduced demethylaing agent, azacytidine (AZA) may be more active in advanced cases of MDS. Early data for the hematologic responses in several stages of MDS supported this. The powerful tool predicting the outcome of MDS is international prognostic scoring system (IPSS). Our study is to compare the response to AZA among the IPSS risk groups using international working group criteria.

Methods: One hundres five patients with MDS were treated with AZA from May 2006 till August 2007. Seven patients had insufficient data. Finally, 108 patients were enrolled.

Results: Their median age was 59 years-old (range; 20∼83), and male to female ratio was 2.09. The previous hematologic diseases documented in 8 patients; apalastic anemia (7), and megaloblstic anemia (1). The secondary MDS occurred in 3 patients; after the chemotherapy (2) and radiotherapy (1). A median time from the diagnosis to treatment was 3 months (0∼183). The previous treatment (percentage of patients given) was the transfusion of RBC (74%) and PLT (35%), oxymetholone (17%), steroid (13%), erythropoietin (7%), cyclosporine (7%), ATG (5%), valproic acid (5%), chemotherapy (3%), and allogeneic SCT (2%). Their ECOG performance scale was 0 (58 patients), 1 (45) and 2 (5), respectively. Their diagnoses just before the AZA were RA (20 patients), RARS (5), RCMD (27), RCMD-RS (6), RAEB-1 (27), RAEB-2 (20), MDS-U (1), MDS with isolated 5q− (1) and CMMoL (1). A number of patients with a LOW, INT-1, INT-2, and HIGH risk was 4 (4%). 70 (65%) 23 (21%) and 11 (10%), respectively. The rate of hematologic response (CR+PR+marrow CR+HI) and cytogenetic response (continued normal karyotype and CR) were similar; 100%/75%/93%/67% and 100%/59%/50%/50% in LOW/INT-1/INT-2/HIGH risk groups, respectively. There were 6 treat-related mortalities, and their causes of death were infection in 4 patients and bleeding in 2 patients. Two patients stopped after one cycle of treatment because of grade 4 hepatoxicity and pulmonary toxicity, respectively. During a median follow-up of 9 months, 4 patients were confirmed as transformation to AML and 1 patient suffered from persistent marrow aplasia. One-year expected overall and failure-free survival was 82 ± 5% and 79 ± 6%, respectively in 108 patients.

Conclusion: AZA showed the equal activity in 4 risk groups on IPSS in patients with MDS. Not only the hematologic response but the cytogenetic response was similar between 4 groups.