Clinical impact of genetic alterations including germline DDX41 mutations in MDS/low-blast count AML patients treated with azacitidine-based regimens

Myelodysplastic syndromes (MDS) patients stratification was based on International Prognostic Scoring System (IPSS) and Revised IPSS (IPSS-R). Recently, a model integrating the mutational status of 31 genes (IPSS-M) refined overall survival (OS) and acute myeloid leukemia (AML) free survival (AMLFS) predictions [1,2,3,4]. The large number of parameters required in IPSS-M may limit its applicability and other groups reported that genetic stratification with smaller gene panel could efficiently predict outcome [5]. Only few studies evaluated the predictive impact of IPSS-M in MDS patients treated with hypomethylating agents (HMA) including azacitidine (AZA), the only available drugs for higher-risk (HR) MDS.

Germline DDX41 mutations (DDX41^MutGL) represent the most frequent genetic predisposition to myeloid neoplasms (MN), accounting for 3–8% adult patients [6,7,8]. Several studies reported DDX41^MutGL MN as specific entities [6, 7], with favorable outcome in cohorts receiving heterogeneous treatments [6, 8] or intensive chemotherapy [7]. Thus, we sought to investigate the prognostic impact of genetic alterations including DDX41^MutGL in a large cohort of MDS/low-blast (LB) count AML patients treated with AZA-based regimens in two prospective randomized trials.

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