Female and preserved platelet count subgroups of myelodysplastic syndrome patients benefit from standard-dose azacitidine

Background: Hypomethylating agents, including azacytidine (AZA), are standard therapeutics for patients with high-risk myelodysplastic syndromes (MDS), a group of myeloid neoplasms. However, treatment schedules are not unified in real-world practice; in addition to the standard 7-day (standard-dose) schedule, shortened (reduced-dose) schedules are also used.Aims: The aim of this study was to discover the patient group(s) which show differential efficacy between standard-and reduced-dose AZA to MDS.Methods and Results: The outcome of different AZA doses in a cohort of 151 MDS patients were retrospectively analyzed. Overall survival (OS) was not significantly different between standard- and reduced-dose AZA groups by multivariate analysis. However, an interaction was found between either the sex (female vs. male), the platelet counts (< 40 x 10(3)/mu l vs. >= 40 x 10(3)/mu l), or the karyotype risk (< poor vs. >= poor) and standard-dose AZA for longer OS. Subgroup analyses revealed better OS with standard- over reduced-dose AZA in female patients (HR, 0.27 [95% CI, 0.090-0.79]; p = 0.011), and those with platelet counts >= 40 x 10(3)/mu l (HR, 0.51 [95% CI, 0.26-0.99]; p = 0.041). The union of female and preserved platelet count subgroups also benefited from standard-dose AZA. With this as a test cohort, we next analyzed patients registered in the JALSG MDS212 study, for whom 7-day and 5-day AZA treatment strategies were prospectively compared, as a validation cohort (N = 172). That cohort showed the same tendency as the retrospective results.Conclusion: We identified the union of female and preserved platelet count subgroups which benefited from standard-dose AZA, imparting crucial information to physicians planning treatment regimens in MDS patients.